61 results on '"Hyunjoon Kong"'
Search Results
2. Self-locomotive, antimicrobial microrobot (SLAM) swarm for enhanced biofilm elimination
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Yu-Heng Deng, Tomas Ricciardulli, Jungeun Won, Matthew A. Wade, Simon A. Rogers, Stephen A. Boppart, David W. Flaherty, and Hyunjoon Kong
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Biomaterials ,Mechanics of Materials ,Biophysics ,Ceramics and Composites ,Bioengineering - Abstract
Biofilm is a major cause of infections and infrastructure deterioration, largely due to molecular diffusion restrictions that hamper the antimicrobial activity of traditional antibiotics and disinfectants. Here, we present a self-locomotive, antimicrobial microrobot (SLAM) swarm that can penetrate, fracture, and detach biofilm and, in turn, nullify bacterial resistance to antibiotics. The SLAM is assembled by loading a controlled mass of manganese oxide nanosheets on diatoms with the polydopamine binder. In hydrogen peroxide solution, SLAMs produce oxygen bubbles that generate thrust to penetrate the rigid and dense Pseudomonas aeruginosa biofilm and self-assemble into a swarm that repeatedly surrounds, expands, and bursts oxygen bubbles. The resulting cavities continue to deform and fracture extracellular polymeric substances from microgrooved silicone substrates and wounded skin explants while decreasing the number of viable bacterial cells. Additionally, SLAM allows irrigating water or antibiotics to access the residual biofilm better, thus enhancing the synergistic efficacy in killing up to 99.9% of bacterial cells. more...
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- 2022
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3. Extracellular Microenvironmental Control for Organoid Assembly
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Kathryn M. Sullivan, Eunkyung Ko, Eun Mi Kim, William C. Ballance, John D. Ito, Madeleine Chalifoux, Young Jun Kim, Rashid Bashir, and Hyunjoon Kong
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Biomaterials ,Biomedical Engineering ,Bioengineering ,Biochemistry - Abstract
Organoids, which are multicellular clusters with similar physiological functions to living organs, have gained increasing attention in bioengineering. As organoids become more advanced, methods to form complex structures continue to develop. There is evidence that the extracellular microenvironment can regulate organoid quality. The extracellular microenvironment consists of soluble bioactive molecules, extracellular matrix, and biofluid flow. However, few efforts have been made to discuss the microenvironment optimal to engineer specific organoids. Therefore, this review article examines the extent to which engineered extracellular microenvironments regulate organoid quality. First, we summarize the natural tissue and organ's unique chemical and mechanical properties, guiding researchers to design an extracellular microenvironment used for organoid engineering. Then, we summarize how the microenvironments contribute to the formation and growth of the brain, lung, intestine, liver, retinal, and kidney organoids. The approaches to forming and evaluating the resulting organoids are also discussed in detail. Impact statement Organoids, which are multicellular clusters with similar physiological function to living organs, have been gaining increasing attention in bioengineering. As organoids become more advanced, methods to form complex structures continue to develop. This review article focuses on recent efforts to engineer the extracellular microenvironment in organoid research. We summarized the natural organ's microenvironment, which informs researchers of key factors that can influence organoid formation. Then, we summarize how these microenvironmental controls significantly contribute to the formation and growth of the corresponding brain, lung, intestine, liver, retinal, and kidney organoids. The approaches to forming and evaluating the resulting organoids are discussed in detail, including extracellular matrix choice and properties, culture methods, and the evaluation of the morphology and functionality through imaging and biochemical analysis. more...
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- 2022
4. Empowering engineered muscle in biohybrid pump by extending connexin 43 duration with reduced graphene oxides
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Eunkyung Ko, Onur Aydin, Zhengwei Li, Lauren Gapinske, Kai-Yu Huang, Taher Saif, Rashid Bashir, and Hyunjoon Kong
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Biomaterials ,Mechanics of Materials ,Biophysics ,Ceramics and Composites ,Bioengineering - Abstract
Engineered skeletal muscle act as therapeutics invaluable to treat injured or diseased muscle and a "living" material essential to assemble biological machinery. For normal development, skeletal myoblasts should express connexin 43, one of the gap junction proteins that promote myoblast fusion and myogenesis, during the early differentiation stage. However, myoblasts cultured in vitro often down-regulate connexin 43 before differentiation, limiting myogenesis and muscle contraction. This study demonstrates that tethering myoblasts with reduced graphene oxide (rGO) slows connexin 43 regression during early differentiation and increases myogenic mRNA synthesis. The whole RNA sequencing also confirms that the rGO on cells increases regulator genes for myogenesis, including troponin, while decreasing negative regulator genes. The resulting myotubes generated a three-fold larger contraction force than the rGO-free myotubes. Accordingly, a valveless biohybrid pump assembled with the rGO-tethered muscle increased the fluid velocity and flow rate considerably. The results of this study would provide an important foundation for developing physiologically relevant muscle and powering up biomachines that will be used for various bioscience studies and unexplored applications. more...
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- 2022
5. Surface tethering of stem cells with H2O2-responsive anti-oxidizing colloidal particles for protection against oxidation-induced death
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Jye Yng Teo, Hyunjoon Kong, Eunkyung Ko, Yongbeom Seo, Yi Yan Yang, Yu Tong Hong, and Jiayu Leong
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0303 health sciences ,Antioxidant ,medicine.medical_treatment ,Mesenchymal stem cell ,Biophysics ,Bioengineering ,02 engineering and technology ,Oxidative phosphorylation ,Epigallocatechin gallate ,021001 nanoscience & nanotechnology ,Cell biology ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,chemistry ,Mechanics of Materials ,Oxidizing agent ,Ceramics and Composites ,medicine ,Secretion ,Stem cell ,0210 nano-technology ,Hydrogen peroxide ,030304 developmental biology - Abstract
Mesenchymal stem cells are the new generation of medicine for treating numerous vascular diseases and tissue defects because of their ability to secrete therapeutic factors. Poor cellular survival in an oxidative diseased tissue, however, hinders the therapeutic efficacy. To this end, we hypothesized that tethering the surface of stem cells with colloidal particles capable of discharging antioxidant cargos in response to elevated levels of hydrogen peroxide (H2O2) would maintain survival and therapeutic activity of the stem cells. We examined this hypothesis by encapsulating epigallocatechin gallate (EGCG) and manganese oxide (MnO2) nanocatalysts into particles comprising poly(d,l-lactide-co-glycolide)-block-hyaluronic acid. The MnO2 nanocatalysts catalyzed the decomposition of H2O2 into oxygen gas, which increased the internal pressure of particles and accelerated the release of EGCG by 1.5-fold. Consequently, stem cells exhibited 1.2-fold higher metabolic activity and 2.8-fold higher secretion level of pro-angiogenic factor in sub-lethal H2O2 concentrations. These stem cells, in turn, performed a greater angiogenic potential with doubled number of newly formed mature blood vessels. We envisage that the results of this study will contribute to improving the therapeutic efficacy of a wide array of stem cells. more...
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- 2019
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6. Modulation of Matrix Softness and Interstitial Flow for 3D Cell Culture Using a Cell-Microenvironment-on-a-Chip System
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Kyeonggon Shin, Hyunjoon Kong, Bumsoo Han, Dong Hyun Kim, Altug Ozcelikkale, Min Kyung Lee, Nicholas E. Clay, Max H. Rich, and OpenMETU
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0301 basic medicine ,Tumor microenvironment ,Materials science ,Biomedical Engineering ,Stiffness ,Matrix (biology) ,Chip ,Biomaterials ,03 medical and health sciences ,3D cell culture ,030104 developmental biology ,0302 clinical medicine ,In vivo ,Cell culture ,030220 oncology & carcinogenesis ,medicine ,medicine.symptom ,Immunostaining ,Biomedical engineering - Abstract
In the past several decades, significant efforts have been devoted to recapitulating the in vivo tissue microenvironment within an in vitro platform. However, it is still challenging to recreate de novo tissue with physiologically relevant matrix properties and fluid flow. To this end, this study demonstrates a method to independently tailor matrix stiffness and interstitial fluid flow using a cell-microenvironment-on-a-chip (C-MOC) platform. Collagen-polyethylene glycol gels tailored to present controlled stiffness and hydraulic conductivity were fabricated in a microfluidic chip. The chip was assembled to continuously create a steady flow of media through the gel. In the C-MOC platform, interstitial flow mitigated the effects of matrix softness on breast cancer cell behavior, according to an immunostaining-based analysis of estrogen receptor-α (ER-α), integrin β1, and E-cadherin. This advanced cell culture platform serves to engineer tissue similar to in vitro tissue and contribute to better understanding and regulating of the biological roles of extracellular microenvironments. more...
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- 2021
7. Adaptive biohybrid pumping machine with flow loop feedback
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Zhengwei Li, William C Balance, Md Saddam Hossain Joy, Shrey Patel, Joanne Hwang, Hyunjoon Kong, and M Taher A Saif
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Biomaterials ,Tissue Engineering ,Muscle Fibers, Skeletal ,Biomedical Engineering ,Bioengineering ,Robotics ,General Medicine ,Muscle, Skeletal ,Biochemistry ,Feedback ,Biotechnology - Abstract
Tissue-engineered living machines is an emerging discipline that employs complex interactions between living cells and engineered scaffolds to self-assemble biohybrid systems for diverse scientific research and technological applications. Here, we report an adaptive, autonomous biohybrid pumping machine with flow loop feedback powered by engineered living muscles. The tissue is made from skeletal muscle cells (C2C12) and collagen I/Matrigel matrix, which self-assembles into a ring that compresses a soft hydrogel tube connected at both ends to a rigid fluidic platform. The muscle ring contracts in a repetitive fashion autonomously squeezing the tube, resulting in an impedance pump. The resulting flow is circulated back to the muscle ring forming a feedback loop, which allows the pump to respond to the cues received from the flow it generates and adaptively manage its pumping performances based on the feedback. The developed biohybrid pumping system may have broad utility and impact in health, medicine and bioengineering. more...
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- 2022
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8. Decellularized Matrix Produced by Mesenchymal Stem Cells Modulates Growth and Metabolic Activity of Hepatic Cell Cluster
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Myung-Joo Kim, Seungyun Baik, Joyeon Kim, Youngjun Kim, Hyunjoon Kong, Jooyeon Park, Kathryn Michele Sullivan, and Eunkyung Ko
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0301 basic medicine ,Confluency ,Decellularization ,Materials science ,Mesenchymal stem cell ,Cell ,Biomedical Engineering ,Spheroid ,Cell biology ,Biomaterials ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Stroma ,Organoid ,Hepatic stellate cell ,medicine ,Biomedical engineering - Abstract
Miniature organlike three-dimensional cell clusters often called organoids have emerged as a useful tool for both fundamental and applied bioscience studies. However, there is still a great need to improve the quality of organoids to a level where they exhibit similar biological functionality to an organ. To this end, we hypothesized that a decellularized matrix derived from mesenchymal stem cell (MSC) could regulate the phenotypic and metabolic activity of organoids. This hypothesis was examined by culturing cells of interest in the decellularized matrix of MSCs cultured on a 2D substrate at confluency or in the form of spheroids. The decellularized matrix prepared with MSC spheroids showed a 3D porous structure with a higher content of extracellular matrix molecules than the decellularized matrix derived from MSCs cultured on a 2D substrate. HepG2 hepatocarcinoma cells, which retain the metabolic activity of hepatocytes, were cultured in these decellularized matrices. Interestingly, the decellularized matrix from the MSC spheroids served to develop the hepatic cell clusters with higher levels of E-cadherin-mediated cell-cell adhesion and detoxification activity than the decellularized matrix from the MSCs cultured on a 2D substrate. Overall, the results of this study are useful in improving biological functionality of a wide array of organoids. more...
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- 2017
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9. Effects of fluoride-modified titanium surfaces with the similar roughness on RUNX2 gene expression of osteoblast-like MG63 cells
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Ji Hyoun Lee, Young-Jun Lim, Jai-Young Koak, Ho Beom Kwon, Hyunjoon Kong, and Myung-Joo Kim
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0301 basic medicine ,Materials science ,Surface Properties ,Biomedical Engineering ,Gene Expression ,chemistry.chemical_element ,Biocompatible Materials ,Cell Count ,Core Binding Factor Alpha 1 Subunit ,Surface finish ,Biomaterials ,Fluorides ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hydrofluoric acid ,medicine ,Humans ,Cell Proliferation ,Titanium ,Osteoblasts ,Metallurgy ,Metals and Alloys ,Chemical modification ,Osteoblast ,030206 dentistry ,Titanium oxide ,030104 developmental biology ,medicine.anatomical_structure ,Chemical engineering ,chemistry ,Wettability ,Ceramics and Composites ,Wetting ,Fluoride - Abstract
Chemical modification of titanium surfaces by hydrofluoric acid (HF) is an effective method to improve bone responses on titanium implant surfaces. In this study, titanium disks were sandblasted with titanium oxide grits and modified with 0.2% and 0.4% of diluted HF under different exposure times of 40 and 60 s. Surface characteristics, such as surface chemical composition, surface topography, and surface wettability, were investigated. To examine MG63 osteoblast-like cell responses to fluoride-modified titanium surfaces with roughness similar to that of nonmodified surfaces, a cell proliferation assay was performed and gene expression levels of Runx2 were evaluated using real-time PCR. Fluoride-modified titanium surfaces revealed no significant roughness difference but with hydrophilic properties than control group SB. Moreover, the relative atomic concentration percentages of fluoride were 0.7, 1.5, and 2.8. As fluoride concentrations increased, surface wettability increased and cell proliferation began earlier. However, the gene expression levels of Runx2 increased earlier on surfaces with 1.5% fluoride, with significantly high surface skewness. There seems to be an optimal fluoride concentration percentage when gene expression levels of Runx2 were taken into consideration. In addition, surface parameters, such as surface wettability and surface skewness, seem to be important factors in the enhancement of osteoblast differentiation by HF. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3102-3109, 2017. more...
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- 2017
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10. Comparative effects of N-cadherin protein and peptide fragments on mesenchymal stem cell mechanotransduction and paracrine function
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Vinh H. Vu, Hyunjoon Kong, Poonam Sehgal, Deborah E. Leckband, Ellen C. Qin, and Syeda Tajin Ahmed
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Vascular Endothelial Growth Factor A ,medicine.medical_treatment ,Biophysics ,Bioengineering ,02 engineering and technology ,Mechanotransduction, Cellular ,Biomaterials ,03 medical and health sciences ,Paracrine signalling ,Extracellular ,medicine ,Mechanotransduction ,030304 developmental biology ,0303 health sciences ,Chemistry ,Cadherin ,Growth factor ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Adhesion ,021001 nanoscience & nanotechnology ,Cadherins ,Peptide Fragments ,Cell biology ,Mechanics of Materials ,Ceramics and Composites ,0210 nano-technology ,Intracellular - Abstract
The recent interest in exploiting cadherin-derived fragments to mimic intercellular adhesion in engineered hybrid biomaterials raises questions about which cadherin constructs effectively mimic cadherin interactions. This study compared the biophysical properties of and signaling initiated by three different, immobilized N-cadherin-derived fragments, in order to identify a minimal construct that mimics intercellular adhesion in biomaterials. Specifically, we compared: i) the full N-cadherin extracellular region with all five ectodomains (EC1-5), ii) the first two ectodomains (EC1-2) of N-cadherin, and iii) a peptide containing the histidine-alanine-valine-aspartic acid-valine (HAVDI) sequence in the first extracellular domain. Comparisons of the binding kinetics and affinities between each of these ligands and N-cadherin expressed on mesenchymal stem cells (MSCs) revealed quantitative differences. Nevertheless, MSCs exhibited similar, rigidity-dependent spreading and traction forces when cultured on gels displaying any of these N-cadherin ligands. There were, however, differences in cell signaling and secretory activities. MSCs cultured on the full N-cadherin extracellular domain (EC1-5) exhibited stiffness-dependent changes in nuclear YAP/TAZ localization and significantly higher secretion of vascular endothelial growth factor and insulin growth factor 1, compared to cells cultured on hydrogels displaying either EC1-2 or the HAVDI peptide. The increased paracrine secretion also enhanced myogenic differentiation. These findings reveal functional differences between N-cadherin derived ligands important for the design of biomaterials that mimic intercellular adhesion. more...
- Published
- 2019
11. Reactive oxygen species-responsive drug delivery systems for the treatment of neurodegenerative diseases
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Hee Jung Chung, Ellen C. Qin, William C. Ballance, Hyunjoon Kong, and Martha U. Gillette
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medicine.medical_specialty ,Inflammatory response ,Biophysics ,Bioengineering ,02 engineering and technology ,Nervous System ,Article ,Biomaterials ,03 medical and health sciences ,Drug Delivery Systems ,Neural drug delivery systems ,medicine ,Animals ,Humans ,Intensive care medicine ,Neuroinflammation ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Reactive oxygen species ,business.industry ,Neurodegenerative Diseases ,021001 nanoscience & nanotechnology ,Review article ,chemistry ,Mechanics of Materials ,Drug delivery ,Ceramics and Composites ,0210 nano-technology ,business ,Reactive Oxygen Species - Abstract
Various neurodegenerative diseases and disorders as well as sleep deprivation seriously impact memory and cognition and can become life-threatening. Current medical techniques attempt to combat these detrimental effects mainly through the administration of neuromedicine. However, drug efficacy is limited by rapid dispersal of the drugs to off-target sites while the site of administration is prone to overdose. Many neuropathological conditions are accompanied by excessive reactive oxygen species (ROS) due to the inflammatory response. Accordingly, ROS-responsive drug delivery systems have emerged as a promising solution. To guide intelligent and comprehensive design of ROS-responsive drug delivery systems, this review article discusses the two following topics: (1) the biology of ROS in both healthy and diseased nervous systems and (2) recent developments in ROS-responsive, drug delivery system design. Overall, this review article would assist efforts to make better decisions about designing ROS-responsive, neural drug delivery systems, including the selection of ROS-responsive functional groups and disease-homing ligands. more...
- Published
- 2019
12. 3D Printed Stem-Cell-Laden, Microchanneled Hydrogel Patch for the Enhanced Release of Cell-Secreting Factors and Treatment of Myocardial Infarctions
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Luke Knapp, Min Kyung Lee, Hyunjoon Kong, Tor W. Jensen, Lawrence B. Schook, Rashid Bashir, Larissa Reinkensmeyer, Jooyeon Park, Caroline Cvetkovic, Jordan Flewellyn, and Molly Melhem
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0301 basic medicine ,3d printed ,Materials science ,Myocardial tissue ,Mesenchymal stem cell ,Cell ,Biomedical Engineering ,Ischemia ,medicine.disease ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Fibrosis ,medicine ,Stem cell ,Ethylene glycol ,Biomedical engineering - Abstract
Over the past several years, biomaterials loaded with mesenchymal stem cells (MSCs) have increasingly been used to reduce the myocardial fate of postinfarction collagen deposition and scar tissue formation. Despite successful gains, therapeutic efficacy has remained limited because of restricted transport of cell-secreting factors at the site of implantation. We hypothesized that an MSC-laden hydrogel patch with multiple microchannels would retain transplanted cells on target tissue and support transport of cell-secreting factors into tissue. By doing so, the gel patch will improve the therapeutic potential of the cells and minimize the degradation of myocardial tissue postinfarction. To examine this hypothesis, a stereolithographic apparatus (SLA) was used to introduce microchannels of controlled diameters (e.g., 500 and 1000 μm) during in situ cross-linking reaction of poly(ethylene glycol)dimethacrylate solution suspended with cells. Placement of the MSC-laden, microchanneled gel patch on the occluded left coronary artery in a murine model showed significant improvement in the ejection fraction, fractional shortening, and stroke volume, compared with gel patches without MSCs and MSC-laden gel patches without microchannels. In particular, the microchannels significantly reduced the number of cells required to recover cardiac function, while minimizing cardiac remodeling. In sum, the microchanneled gel patch would provide a means to prevent abnormal fibrosis resulting from acute ischemic injury. more...
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- 2016
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13. Graphene oxide substrates with N-cadherin stimulates neuronal growth and intracellular transport
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Tauseef B. Shah, Evangelos Liamas, Zhenyu Zhang, Mikhail E. Kandel, Hyunjoon Kong, Deborah E. Leckband, Martha U. Gillette, Ellen C. Qin, Chaeyeon Kim, Collin D. Kaufman, and Gabriel Popescu
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Neurite ,Neurogenesis ,0206 medical engineering ,Biomedical Engineering ,Biological Transport, Active ,Nerve Tissue Proteins ,02 engineering and technology ,Biochemistry ,Actin cytoskeleton organization ,Biomaterials ,medicine ,Cell Adhesion ,Neurites ,Animals ,Rats, Long-Evans ,Cell adhesion ,Molecular Biology ,Actin ,Chemistry ,Cadherin ,General Medicine ,Adhesion ,021001 nanoscience & nanotechnology ,Cadherins ,020601 biomedical engineering ,Rats ,medicine.anatomical_structure ,Biophysics ,Graphite ,Neuron ,0210 nano-technology ,Intracellular ,Biotechnology - Abstract
Intracellular transport is fundamental for neuronal function and development and is dependent on the formation of stable actin filaments. N-cadherin, a cell-cell adhesion protein, is actively involved in neuronal growth and actin cytoskeleton organization. Various groups have explored how neurons behaved on substrates engineered to present N-cadherin; however, few efforts have been made to examine how these surfaces modulate neuronal intracellular transport. To address this issue, we assembled a substrate to which recombinant N-cadherin molecules are physiosorbed using graphene oxide (GO) or reduced graphene oxide (rGO). N-cadherin physisorbed on GO and rGO led to a substantial enhancement of intracellular mass transport along neurites relative to N-cadherin on glass, due to increased neuronal adhesion, neurite extensions, dendritic arborization and glial cell adhesion. This study will be broadly useful for recreating active neural tissues in vitro and for improving our understanding of the development, homeostasis, and physiology of neurons. STATEMENT OF SIGNIFICANCE: Intracellular transport of proteins and chemical cues is extremely important for culturing neurons in vitro, as they replenish materials within and facilitate communication between neurons. Various studies have shown that intracellular transport is dependent on the formation of stable actin filaments. However, the extent to which cadherin-mediated cell-cell adhesion modulates intracellular transport is not heavily explored. In this study, N-cadherin was adsorbed onto graphene oxide-based substrates to understand the role of cadherin at a molecular level and the intracellular transport within cells was examined using spatial light interference microscopy. As such, the results of this study will serve to better understand and harness the role of cell-cell adhesion in neuron development and regeneration. more...
- Published
- 2018
14. High-Resolution Projection Microstereolithography for Patterning of Neovasculature
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Min Kyung Lee, Gabriel Popescu, Mustafa Mir, Hyunjoon Kong, Artem Shkumatov, Basanta Bhaduri, Rashid Bashir, and Ritu Raman
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Vascular Endothelial Growth Factor A ,0301 basic medicine ,Stromal cell ,Materials science ,Cell Survival ,Biomedical Engineering ,Neovascularization, Physiologic ,Pharmaceutical Science ,02 engineering and technology ,Regenerative medicine ,Chorioallantoic Membrane ,Hydrogel, Polyethylene Glycol Dimethacrylate ,law.invention ,Biomaterials ,Extracellular matrix ,Mice ,03 medical and health sciences ,Imaging, Three-Dimensional ,Tissue engineering ,law ,medicine ,Animals ,Cells, Cultured ,Stereolithography ,Bioprinting ,021001 nanoscience & nanotechnology ,Chorioallantoic membrane ,030104 developmental biology ,medicine.anatomical_structure ,Self-healing hydrogels ,Bone marrow ,0210 nano-technology ,Chickens ,Biomedical engineering - Abstract
To gain a quantitative understanding of the way cells sense, process, and respond to dynamic environmental signals in real-time requires developing in vitro model systems that accurately replicate the 3D structure and function of native tissue. A high-resolution projection stereolithography apparatus (μSLA) capable of multimaterial and grayscale 3D patterning of cells and biomaterials at more...
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- 2015
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15. Poly(ethylene glycol)-poly(lactic-co-glycolic acid) core–shell microspheres with enhanced controllability of drug encapsulation and release rate
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Hyunjoon Kong, Chaenyung Cha, and Jae Hyun Jeong
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Vascular Endothelial Growth Factor A ,Drug ,Materials science ,Polyesters ,media_common.quotation_subject ,Biomedical Engineering ,Biophysics ,Bioengineering ,Nanotechnology ,macromolecular substances ,Chorioallantoic Membrane ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Drug Delivery Systems ,PEG ratio ,Animals ,Glycolic acid ,media_common ,Drug Implants ,technology, industry, and agriculture ,Proteins ,Hydrogels ,Serum Albumin, Bovine ,Microspheres ,Drug Liberation ,PLGA ,chemistry ,Chemical engineering ,Drug delivery ,Self-healing hydrogels ,Angiogenesis Inducing Agents ,Drug carrier ,Chickens ,Ethylene glycol - Abstract
Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely used as drug carriers for minimally invasive, local, and sustained drug delivery. However, their use is often plagued by limited controllability of encapsulation efficiency, initial burst, and release rate of drug molecules, which cause unsatisfactory outcomes and several side effects including inflammation. This study presents a new strategy of tuning the encapsulation efficiency and the release rate of protein drugs from a PLGA microsphere by filling the hollow core of the microsphere with poly(ethylene glycol) (PEG) hydrogels of varying cross-linking density. The PEG gel cores were prepared by inducing in situ cross-linking reactions of PEG monoacrylate solution within the PLGA microspheres. The resulting PEG-PLGA core-shell microspheres exhibited (1) increased encapsulation efficiency, (2) decreased initial burst, and (3) a more sustained release of protein drugs, as the cross-linking density of the PEG gel core was increased. In addition, implantation of PEG-PLGA core-shell microspheres encapsulated with vascular endothelial growth factor (VEGF) onto a chicken chorioallantoic membrane resulted in a significant increase in the number of new blood vessels at an implantation site, while minimizing inflammation. Overall, this strategy of introducing PEG gel into PLGA microspheres will be highly useful in tuning release rates and ultimately in improving the therapeutic efficacy of a wide array of protein drugs. more...
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- 2015
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16. Water–Hydrogel Binding Affinity Modulates Freeze-Drying-Induced Micropore Architecture and Skeletal Myotube Formation
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Hyunjoon Kong, Nicholas E. Clay, Jinrong Chen, Marni D. Boppart, Nicholas M. Marshall, Min Kyung Lee, Ziad S. Mahmassani, and Max H. Rich
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Polymers and Plastics ,Alginates ,Muscle Fibers, Skeletal ,Cell Culture Techniques ,Bioengineering ,Methacrylate ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Freeze-drying ,Glucuronic Acid ,Tissue engineering ,Polymer chemistry ,Materials Chemistry ,Muscle, Skeletal ,3-Mercaptopropionic Acid ,Polyhydroxyethyl Methacrylate ,chemistry.chemical_classification ,Tissue Engineering ,Chemistry ,Hexuronic Acids ,technology, industry, and agriculture ,Water ,Polymer ,Microporous material ,Freeze Drying ,Chemical engineering ,Self-healing hydrogels ,Water binding ,Ethylene glycol - Abstract
Freeze-dried hydrogels are increasingly used to create 3D interconnected micropores that facilitate biomolecular and cellular transports. However, freeze-drying is often plagued by variance in micropore architecture based on polymer choice. We hypothesized that water-polymer binding affinity plays a significant role in sizes and numbers of micropores formed through freeze-drying, influencing cell-derived tissue quality. Poly(ethylene glycol)diacrylate (PEGDA) hydrogels with alginate methacrylate (AM) were used due to AM's higher binding affinity for water than PEGDA. PEGDA-AM hydrogels with larger AM concentrations resulted in larger sizes and numbers of micropores than pure PEGDA hydrogels, attributed to the increased mass of water binding to the PEGDA-AM gel. Skeletal myoblasts loaded in microporous PEGDA-AM hydrogels were active to produce 3D muscle-like tissue, while those loaded in pure PEGDA gels were localized on the gel surface. We propose that this study will be broadly useful in designing and improving the performance of various microporous gels. more...
- Published
- 2015
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17. Engineering Polymersomes for Diagnostics and Therapy
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Hyunjoon Kong, Vinay K. Aakalu, Jye Yng Teo, Jiayu Leong, and Yi Yan Yang
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Drug Carriers ,Materials science ,Polymers ,Vesicle ,Biomedical Engineering ,Pharmaceutical Science ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Article ,0104 chemical sciences ,Biomaterials ,Polymersome ,Drug delivery ,Animals ,Humans ,Nanoparticles ,Particle Size ,Pathology, Molecular ,0210 nano-technology ,Amphiphilic copolymer - Abstract
Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self-assembly of amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer membrane and hydrophilic core, each of which is loaded with a wide array of small and large molecules of interests. As such, polymersomes are increasingly being studied as carriers of imaging probes and therapeutic drugs. Effective delivery of polymersomes necessitates careful design of polymersomes. Therefore, this review article discusses the design strategies of polymersomes developed for enhanced transport and efficacy of imaging probes and therapeutic drugs. In particular, the article focuses on overviewing technologies to regulate the size, structure, shape, surface activity, and stimuli- responsiveness of polymersomes and discussing the extent to which these properties and structure of polymersomes influence the efficacy of cargo molecules. Taken together with future considerations, this article will serve to improve the controllability of polymersome functions and accelerate the use of polymersomes in biomedical applications. more...
- Published
- 2017
18. Poly(ethylene glycol)-Mediated Collagen Gel Mechanics Regulates Cellular Phenotypes in a Microchanneled Matrix
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Hyunjoon Kong, Min Kyung Lee, Max H. Rich, William C. Ballance, and Marni D. Boppart
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0301 basic medicine ,Polymers and Plastics ,Cellular differentiation ,Myoblasts, Skeletal ,Cell ,Muscle Fibers, Skeletal ,Bioengineering ,02 engineering and technology ,Cell Line ,Polyethylene Glycols ,Biomaterials ,Extracellular matrix ,03 medical and health sciences ,Matrix (mathematics) ,Mice ,Polymer chemistry ,Materials Chemistry ,medicine ,Myocyte ,Animals ,Elastic modulus ,Chemistry ,Cell Differentiation ,021001 nanoscience & nanotechnology ,Phenotype ,Extracellular Matrix ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,Biophysics ,Collagen ,0210 nano-technology ,Gels - Abstract
For the past few decades, efforts have been extensively made to reproduce tissue of interests for various uses including fundamental bioscience studies, clinical treatments, and even soft robotic systems. In these studies, cells are often cultured in micropores introduced in a provisional matrix despite that bulk rigidity may negatively affect cellular differentiation involved in tissue formation. To this end, we hypothesized that suspending cells within a soft fibrous matrix that is encapsulated within the microchannels of a provisional matrix would allow us to mediate effects of the matrix rigidity on cells and, in turn, to increase the cell differentiation level. We examined this hypothesis by filling microchannels interpenetrating alginate matrices with collagen gels of controlled elastic moduli (i.e., 125 to 1 Pa). Myoblasts used as a model predifferentiated cell were suspended within the collagen gels. The elastic modulus of the collagen gels was decreased through the addition of poly(ethylene glycol) during the gel preparation. Myoblasts loaded in the collagen gel exhibited a higher myogenic differentiation level than those adhered to the collagen-coated microchannel wall. Furthermore, the collagen gel softened by poly(ethylene glycol) further increased the volume of the multinucleated myofibers. The role of collagen gel softness on cell differentiation became more significant when the bulk elastic modulus of the alginate matrix was tuned to be close to that of muscle tissue (i.e., 11 kPa). We believe that the results of this study would be useful to understanding phenotypic activities of a wide array of cells involved in tissue development and regeneration. more...
- Published
- 2017
19. Bioactuators: Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators (Adv. Healthcare Mater. 12/2017)
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Yongbeom Seo, Hyunjoon Kong, Alexandra Palasz, Michael Gapinske, Pablo Perez Pinera, Lauren Grant, Caroline Cvetkovic, Ritu Raman, Howard Dabbous, and Rashid Bashir
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Biomaterials ,medicine.anatomical_structure ,Tissue engineering ,business.industry ,Biomedical Engineering ,Pharmaceutical Science ,Medicine ,Skeletal muscle ,Optogenetics ,business ,Biomedical engineering - Published
- 2017
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20. Antioxidants: Stimulus‐Responsive Anti‐Oxidizing Drug Crystals and their Ecological Implication (Small 21/2019)
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Younghak Cho, Youngjun Kim, Seung Jung Yu, Da-Hye Kim, Jiayu Leong, Chang Gyun Park, Eunkyung Ko, Sung Gap Im, Jonghwi Lee, Byoung Soo Kim, and Hyunjoon Kong
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Stimuli responsive ,biology ,Catechin ,General Chemistry ,Drug crystals ,medicine.disease_cause ,biology.organism_classification ,Daphnia ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Oxidizing agent ,medicine ,Biophysics ,General Materials Science ,Oxidative stress ,Biotechnology - Published
- 2019
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21. Stimulus‐Responsive Anti‐Oxidizing Drug Crystals and their Ecological Implication
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Eunkyung Ko, Youngjun Kim, Byoung Soo Kim, Jiayu Leong, Da Hye Kim, Chang Gyun Park, Jonghwi Lee, Sung Gap Im, Younghak Cho, Seung Jung Yu, and Hyunjoon Kong
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Antioxidant ,medicine.medical_treatment ,02 engineering and technology ,Oxidative phosphorylation ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Article ,Antioxidants ,Catechin ,Biomaterials ,chemistry.chemical_compound ,Heart Rate ,medicine ,Animals ,General Materials Science ,chemistry.chemical_classification ,Polyethylenimine ,Reactive oxygen species ,biology ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Oxidative Stress ,Daphnia ,chemistry ,biology.protein ,Biophysics ,Reactive Oxygen Species ,0210 nano-technology ,Intracellular ,Oxidative stress ,Biotechnology ,Peroxidase - Abstract
Various antioxidants are being used to neutralize the harmful effects of reactive oxygen species (ROS) overproduced in the diseased tissue and contaminated environment. Polymer-directed crystallization of antioxidants has attracted attention as a way to control drug efficacy through molecular dissolution. However, most recrystallized antioxidants undertake the continuous dissolution independent of the ROS level, thus causing side-effects. This study demonstrates a unique method to assemble antioxidant crystals that modulate their dissolution rate in response to the ROS level. We hypothesized that antioxidants recrystallized using a ROS-labile polymer would be triggered to dissolve when ROS level increases. We examined this hypothesis by using catechin as a model antioxidant. Catechin was recrystallized using polyethylenimine cross-linked with ROS-labile diselanediylbis-(ethane-2,1-diyl)-diacrylate. Catechin crystallized with ROS-labile polymer displayed accelerated dissolution proportional to the H(2)O(2) concentration. The ROS-responsive catechin crystals protected vascular cells from oxidative insults by activating intracellular glutathione peroxidase expression and, in turn, inhibiting an increase in the intracellular oxidative stress. In addition, the ROS-responsive catechin crystals alleviated changes in the heart rate of Daphnia magna in the oxidative media. We propose that the results of this study would be broadly useful to improving the therapeutic efficacy of a broad array of drug compounds. more...
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- 2019
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22. Interplay of cell adhesion matrix stiffness and cell type for non-viral gene delivery
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Cathy Chu and Hyunjoon Kong
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Stromal cell ,Materials science ,Genetic enhancement ,Biomedical Engineering ,Bone Morphogenetic Protein 2 ,Bone Marrow Cells ,Matrix (biology) ,Gene delivery ,Bone morphogenetic protein ,Biochemistry ,Cell-Matrix Junctions ,Polyethylene Glycols ,Myoblasts ,Biomaterials ,Extracellular matrix ,Mice ,Elastic Modulus ,Cell Adhesion ,Animals ,Cell adhesion ,Cell Shape ,Molecular Biology ,Cell Proliferation ,Fluorescent Dyes ,Cell Nucleus ,Gene Transfer Techniques ,Hydrogels ,DNA ,General Medicine ,Transfection ,Fibroblasts ,Molecular biology ,Fibronectins ,Cell biology ,Viruses ,NIH 3T3 Cells ,Stromal Cells ,Plasmids ,Biotechnology - Abstract
Non-viral gene delivery has the potential to treat a wide array of diseases but has been hindered by limited expression in vivo, possibly due to complex cellular microenvironments at delivery sites. Previous studies have reported that extracellular matrix properties, including stiffness, influence non-viral gene transfection efficiencies. This study reports that the effect of matrix stiffness on non-viral gene delivery differs among cell types due to varying sensitivities to matrix rigidity. Plasmid DNA encoding bone morphogenetic protein (BMP)-2 was delivered to fibroblasts, bone marrow stromal cells, and myoblasts cultured on fibronectin-conjugated poly(ethylene glycol) diacrylate hydrogels with varied elastic moduli, and the cellular uptake and subsequent expression of plasmid DNA were examined. While exogenous BMP-2 expression increased with increasing matrix stiffness for all three cell types, the effects of matrix stiffness were most pronounced for fibroblasts. Mechanistic studies conducted in parallel indicate that matrix stiffness influenced the projected area and nuclear aspect ratio for fibroblasts but had minimal effects on the morphology of bone marrow stromal cells and myoblasts. Overall, we believe that the results of this study will be useful for developing advanced non-viral gene delivery strategies for improved therapeutic efficacy. more...
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- 2012
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23. Characterization of Mass and Swelling of Hydrogel Microstructures using MEMS Resonant Mass Sensor Arrays
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Hyunjoon Kong, Larry J. Millet, Kidong Park, Elise A. Corbin, William P. King, Robert Free, and Rashid Bashir
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Microelectromechanical systems ,chemistry.chemical_classification ,Materials science ,Nanotechnology ,General Chemistry ,Polyethylene glycol ,Polymer ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Volume (thermodynamics) ,Self-healing hydrogels ,medicine ,General Materials Science ,Swelling ,medicine.symptom ,Composite material ,Ethylene glycol ,Microscale chemistry ,Biotechnology - Abstract
The use of hydrogels for biomedical engineering, and for the development of biologically inspired cellular systems at the microscale, is advancing at a rapid pace. Microelectromechanical system (MEMS) resonant mass sensors enable the mass measurement of a range of materials. The integration of hydrogels onto MEMS resonant mass sensors is demonstrated, and these sensors are used to characterize the hydrogel mass and swelling characteristics. The mass values obtained from resonant frequency measurements of poly(ethylene glycol)diacrylate (PEGDA) microstructures match well with the values independently verified through volume measurements. The sensors are also used to measure the influence of fluids of similar and greater density on the mass measurements of microstructures. The data show a size-dependent increase in gel mass when fluid density is increased. Lastly, volume comparisons of bulk hydrogels with a range polymer concentration (5% to 100% (v/v)) show a non-linear swelling trend. more...
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- 2012
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24. Stereolithography-Based Hydrogel Microenvironments to Examine Cellular Interactions
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Hyunjoon Kong, Pinar Zorlutuna, Rashid Bashir, and Jae Hyun Jeong
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Cell type ,Materials science ,Nanotechnology ,Matrix (biology) ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials ,law.invention ,Biomaterials ,3d fabrication ,Tissue engineering ,law ,Self-healing hydrogels ,Electrochemistry ,Biophysics ,Cholinergic ,Myocyte ,Stereolithography - Abstract
A spatially organized three-dimensional (3D) co-culture of multiple cell types is required to recapitulate cellular interactions and microenvironments in complex tissues. Although there are limited reports for 3D patterning of cells and materials, approaches to examine functional interactions of 3D spatially patterned multiple cell types are lacking entirely. This is mostly due to difficulties in controlling the physical arrangement of cells in a 3D matrix and the physical properties of the cell-encapsulating matrix, while keeping the cells alive and functional for extended periods of time. In this study, an automated maskless fabrication technique is combined with a tunable polymer blend to spatially organize primary hippocampus neurons (HNs) and skeletal muscle myoblast cells (MCs) in a 3D hydrogel matrix with tunable mechanical and degradation properties. The spatial organization of these multiple cell types revealed that the presence of MCs resulted in increased cholinergic functionality of the HNs, as quantified by their choline acetyltransferase activity. The presence of a factor alone is not sufficient, but its spatiotemporal control is necessary; a condition that is possibly true for many cellular interactions. Therefore, the system described here offers a different approach to examine such previously unknown interactions. The approach proposed in this study can be used to examine interactions between many different cell types and shift the 3D fabrication paradigm to a next level, which is to fabricate tissues that are not only viable but also functional. more...
- Published
- 2011
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25. Simulation and Fabrication of Stronger, Larger, and Faster Walking Biohybrid Machines
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Emilia Solomon, Mattia Gazzola, Lauren Grant, Hyunjoon Kong, Onur Aydin, Gelson J. Pagan-Diaz, Taher A. Saif, Caroline Cvetkovic, Rashid Bashir, Xiaotian Zhang, Eunkyung Ko, Yongdeok Kim, and Jennifer Hollis more...
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Biomaterials ,Materials science ,Fabrication ,0502 economics and business ,05 social sciences ,Electrochemistry ,Nanotechnology ,010501 environmental sciences ,Condensed Matter Physics ,01 natural sciences ,050203 business & management ,0105 earth and related environmental sciences ,Electronic, Optical and Magnetic Materials - Published
- 2018
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26. Biomimetics: Simulation and Fabrication of Stronger, Larger, and Faster Walking Biohybrid Machines (Adv. Funct. Mater. 23/2018)
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Taher A. Saif, Lauren Grant, Mattia Gazzola, Onur Aydin, Hyunjoon Kong, Rashid Bashir, Eunkyung Ko, Gelson J. Pagan-Diaz, Jennifer Hollis, Caroline Cvetkovic, Yongdeok Kim, Xiaotian Zhang, and Emilia Solomon more...
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Fabrication ,Materials science ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,Biomaterials ,Electrochemistry ,Biomimetics ,0210 nano-technology - Published
- 2018
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27. Decoupled control of stiffness and permeability with a cell-encapsulating poly(ethylene glycol) dimethacrylate hydrogel
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So Youn Kim, Hyunjoon Kong, Chaenyung Cha, and Lan Cao
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Materials science ,Alginates ,Cell Survival ,Biophysics ,Biocompatible Materials ,Bioengineering ,macromolecular substances ,Matrix (biology) ,Methacrylate ,Permeability ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Glucuronic Acid ,Tissue engineering ,Cell Line, Tumor ,Elastic Modulus ,Animals ,Composite material ,Cell encapsulation ,Neurons ,Tissue Engineering ,Hexuronic Acids ,technology, industry, and agriculture ,Hydrogels ,Cells, Immobilized ,Rats ,Transplantation ,chemistry ,Chemical engineering ,Mechanics of Materials ,Permeability (electromagnetism) ,Self-healing hydrogels ,Ceramics and Composites ,Methacrylates ,Ethylene glycol - Abstract
Hydrogels are increasingly used as a cell encapsulation and transplantation device. The successful use of a hydrogel greatly relies on an ability to control hydrogel stiffness which affects structural integrity and regulates cellular phenotypes. However, conventional strategies to increase the gel stiffness lead to decrease in the gel permeability and subsequently deteriorate the viability of cells encapsulated in a gel matrix. This study presents a strategy to decouple the inversed dependency of permeability on the stiffness of a hydrogel by chemically cross-linking methacrylic alginate with poly(ethylene glycol) dimethacrylate (PEGDA). As expected, gel stiffness represented by elastic modulus was tuned over one order of magnitude with the concentration of methacrylic alginate and the degree of substitution of methacrylic groups. In contrast, swelling ratio of the hydrogel indicative of gel permeability was minimally changed because of multiple hydrophilic groups of alginate, similar to function of proteoglycans in a natural extracellular matrix. Furthermore, viability of neural cells encapsulated in a hydrogel of PEGDA and methacrylic alginate rather increased with hydrogel stiffness. Overall, the results of this study demonstrate an advanced biomaterial design paradigm which allows one to culture cells in a 3D matrix of varying rigidity. This study will therefore greatly expedite the use of a hydrogel system in both fundamental studies and clinical settings of cell therapies. more...
- Published
- 2010
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28. Simulation and Fabrication of Stronger, Larger, and Faster Walking Biohybrid Machines
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Onur Aydin, Lauren Grant, Hyunjoon Kong, Yongdeok Kim, Taher A. Saif, Caroline Cvetkovic, Jennifer Hollis, Eunkyung Ko, Mattia Gazzola, Emilia Solomon, Gelson J. Pagan-Diaz, Rashid Bashir, and Xiaotian Zhang more...
- Subjects
0301 basic medicine ,Biomaterials ,03 medical and health sciences ,030104 developmental biology ,Fabrication ,Materials science ,Electrochemistry ,Nanotechnology ,02 engineering and technology ,021001 nanoscience & nanotechnology ,0210 nano-technology ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Published
- 2018
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29. AFM Imaging of RGD Presenting Synthetic Extracellular Matrix Using Gold Nanoparticles
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Susan X. Hsiong, Peter H. Cooke, Maria Ericsson, David J. Mooney, Hyunjoon Kong, and Marshall L. Fishman
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Polymers and Plastics ,Alginates ,Biotin ,Metal Nanoparticles ,Nanoparticle ,Biocompatible Materials ,Bioengineering ,Nanotechnology ,macromolecular substances ,Conjugated system ,Microscopy, Atomic Force ,Biomaterials ,Microscopy, Electron, Transmission ,Tissue engineering ,Materials Chemistry ,Tissue Scaffolds ,Chemistry ,technology, industry, and agriculture ,Biomaterial ,Hydrogels ,Adhesion ,Extracellular Matrix ,Colloidal gold ,Biotinylation ,Self-healing hydrogels ,Microscopy, Electron, Scanning ,Gold ,Streptavidin ,Oligopeptides ,Biotechnology - Abstract
Several high-resolution imaging techniques such as FESEM, TEM and AFM are compared with respect to their application on alginate hydrogels, a widely used polysaccharide biomaterial. A new AFM method applicable to RGD peptides covalently conjugated to alginate hydrogels is described. High-resolution images of RGD adhesion ligand distribution were obtained by labeling biotinylated RGD peptides with streptavidin-labeled gold nanoparticles. This method may broadly provide a useful tool for sECM characterization and design for tissue regeneration strategies. more...
- Published
- 2008
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30. Quantifying Interactions between Cell Receptors and Adhesion Ligand-Modified Polymers in Solution
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Kuen Yong Lee, David J. Mooney, and Hyunjoon Kong
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Polymers and Plastics ,Alginates ,Polymers ,Fluorescence spectrometry ,Analytical chemistry ,Bioengineering ,Biomaterials ,Mice ,Glucuronic Acid ,Cell–cell interaction ,Cell Adhesion ,Fluorescence Resonance Energy Transfer ,Materials Chemistry ,Animals ,Cells, Cultured ,chemistry.chemical_classification ,Tissue Engineering ,Rhodamines ,Ligand ,Hexuronic Acids ,Polymer ,Adhesion ,Fluorescence ,Polyelectrolyte ,Förster resonance energy transfer ,chemistry ,Biophysics ,Rheology ,Oligopeptides ,Biotechnology - Abstract
Specific interactions between cells and cell-interactive polymers in solution were investigated by the fluorescence resonance energy transfer (FRET) technique and rheological measurements. The green fluorescence emission was dramatically reduced when rhodamine-stained cells were mixed with a fluorescein-labeled RGD-alginate solution, compared with those mixed with no RGD-containing alginate solution, which indicated an occurrence of FRET and existence of specific interactions between the cells and the polymers in solution. Rheological measurements also confirmed the formation of ordered structures of cell/polymer mixtures, caused by specific cell-polymer interactions. The FRET method was able to provide a useful means of investigating cell-polymer interactions, both in a qualitative and quantitative manner, and this approach to monitoring and controlling specific interactions between cells and polymers could be useful in the design and tailoring of polymeric carriers for cells, as well as for biological drugs, especially for tissue engineering applications. more...
- Published
- 2008
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31. Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix
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Cristina C. Barrias, Rui Loja Fernandes, David J. Mooney, Marta B. Evangelista, Hyunjoon Kong, Pedro L. Granja, Susan X. Hsiong, Paula Sampaio, Mário A. Barbosa, and Roberto Salema
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Materials science ,Cytoskeleton organization ,Alginates ,Cell Survival ,Cellular differentiation ,Osteocalcin ,Biophysics ,Bioengineering ,Biomaterials ,Extracellular matrix ,Mice ,Glucuronic Acid ,Microscopy, Electron, Transmission ,Bone cell ,Cell Adhesion ,Animals ,Bone regeneration ,Cell encapsulation ,Cytoskeleton ,Cell Proliferation ,Microscopy, Confocal ,Osteoblasts ,biology ,Hexuronic Acids ,Cell Differentiation ,3T3 Cells ,Alkaline Phosphatase ,Microspheres ,Extracellular Matrix ,Cell biology ,Mechanics of Materials ,Ceramics and Composites ,biology.protein ,Alkaline phosphatase ,Oligopeptides ,Biomedical engineering - Abstract
There is a need for new therapeutic strategies to treat bone defects caused by trauma, disease or tissue loss. Injectable systems for cell transplantation have the advantage of allowing the use of minimally invasive surgical procedures, and thus for less discomfort to patients. In the present study, it is hypothesized that Arg-Gly-Asp (RGD)-coupled in a binary (low and high molecular weight) injectable alginate composition is able to influence bone cell differentiation in a three-dimensional (3D) structure. Viability, metabolic activity, cytoskeleton organization, ultrastructure and differentiation (alkaline phosphatase (ALP), von Kossa, alizarin red stainings and osteocalcin quantification) of immobilized cells were assessed. Cells within RGD-modified alginate microspheres were able to establish more interactions with the synthetic extracellular matrix as visualized by confocal laser scanning microscope and transmission electron microscopy imaging, and presented a much higher level of differentiation (more intense ALP and mineralization stainings and higher levels of osteocalcin secretion) when compared to cells immobilized within unmodified alginate microspheres. These findings demonstrate that peptides covalently coupled to alginate were efficient in influencing cell behavior within this 3D system, and may provide adequate preparation of osteoblasts for cell transplantation. more...
- Published
- 2007
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32. Hydrophilic Packaging of Iron Oxide Nanoclusters for Highly Sensitive Imaging
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Hyunjoon Kong, Dawn Ernenwein, Sanjay Misra, Cartney E. Smith, Ju Yeon Lee, Steven C. Zimmerman, Artem Shkumatov, Molly Melhem, and Nicholas E. Clay
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Glycerol ,Male ,Materials science ,Superparamagnetic iron oxide nanoparticles ,Polymers ,Biophysics ,Iron oxide ,Contrast Media ,Bioengineering ,Ferric Compounds ,Article ,Nanoclusters ,Cell Line ,Biomaterials ,chemistry.chemical_compound ,Ischemia ,medicine ,Animals ,Magnetite Nanoparticles ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Hyperbranched polyglycerol ,medicine.diagnostic_test ,Target tissue ,Magnetic resonance imaging ,Polymer ,Magnetic Resonance Imaging ,Highly sensitive ,Hindlimb ,chemistry ,Mechanics of Materials ,Ceramics and Composites ,Hydrophobic and Hydrophilic Interactions ,Biomedical engineering - Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging probes to provide contrast in magnetic resonance images. Successful use of SPIONs in targeted applications greatly depends on their ability to generate contrast, even at low levels of accumulation, in the tissue of interest. In the present study, we report that SPION nanoclusters packaged to a controlled size by a hyperbranched polyglycerol (HPG) can target tissue defects and have a high relaxivity of 719 mM(-1) s(-1), which was close to their theoretical maximal limit. The resulting nanoclusters were able to identify regions of defective vasculature in an ischemic murine hindlimb using MRI with iron doses that were 5-10 fold lower than those typically used in preclinical studies. Such high relaxivity was attributed to the molecular architecture of HPG, which mimics that of the water retentive polysaccharide, glycogen. The results of this study will be broadly useful in sensitive imaging applications. more...
- Published
- 2015
33. A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion ligands regulates 3D spatial organization of cells and tissue
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Hyunjoon Kong, Max H. Rich, Min Kyung Lee, and Jonghwi Lee
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Vascular Endothelial Growth Factor A ,Stromal cell ,Materials science ,Cell ,Biophysics ,Cell Culture Techniques ,Bioengineering ,Biocompatible Materials ,Bone Marrow Cells ,Chick Embryo ,Matrix (biology) ,Ligands ,Chorioallantoic Membrane ,Biomaterials ,3D cell culture ,Mice ,Biomimetics ,Materials Testing ,medicine ,Cell Adhesion ,Animals ,Humans ,Cell adhesion ,chemistry.chemical_classification ,Tissue Engineering ,Biomolecule ,Hydrogels ,Mesenchymal Stem Cells ,Microspheres ,medicine.anatomical_structure ,chemistry ,Mechanics of Materials ,Self-healing hydrogels ,Ceramics and Composites ,NIH 3T3 Cells ,Anisotropy ,Stress, Mechanical ,Stem cell ,Oligopeptides ,Biomedical engineering - Abstract
Bioactive hydrogels have been extensively studied as a platform for 3D cell culture and tissue regeneration. One of the key desired design parameters is the ability to control spatial organization of biomolecules and cells and subsequent tissue in a 3D matrix. To this end, this study presents a simple but advanced method to spatially organize microchanneled, cell adherent gel blocks and non-adherent ones in a single construct. This hydrogel system was prepared by first fabricating a bimodal hydrogel in which the microscale, alginate gel blocks modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD peptides), and those free of RGD peptides, were alternatingly presented. Then, anisotropically aligned microchannels were introduced by uniaxial freeze-drying of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal cells to adhere to and differentiate into neuron and glial cells exclusively in microchannels of the alginate gel blocks modified with RGD peptides. Separately, the bimodal gel loaded with microparticles releasing vascular endothelial growth factor stimulated vascular growth solely into microchannels of the RGD-alginate gel blocks in vivo. These results were not attained by the bimodal hydrogel fabricated to present randomly oriented micropores. Overall, the bimodal gel system could regulate spatial organization of nerve-like tissue or blood vessels at sub-micrometer length scale. We believe that the hydrogel assembly demonstrated in this study will be highly useful in developing a better understanding of diverse cellular behaviors in 3D tissue and further improve quality of a wide array of engineered tissues. more...
- Published
- 2015
34. Alginate Hydrogels as Biomaterials
- Author
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Alexander Augst, Hyunjoon Kong, and David J. Mooney
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Polymers and Plastics ,Alginates ,Biocompatible Materials ,Bioengineering ,Nanotechnology ,Biomaterials ,Drug Delivery Systems ,Glucuronic Acid ,Tissue engineering ,In vivo ,Carbohydrate Conformation ,Materials Chemistry ,medicine ,Tissue Engineering ,Chemistry ,Hexuronic Acids ,Biomaterial ,Hydrogels ,Adhesion ,Polyelectrolyte ,Transplantation ,Swelling ,medicine.symptom ,Drug carrier ,Biotechnology ,Biomedical engineering - Abstract
[Image: see text] Alginate hydrogels are proving to have a wide applicability as biomaterials. They have been used as scaffolds for tissue engineering, as delivery vehicles for drugs, and as model extracellular matrices for basic biological studies. These applications require tight control of a number of material properties including mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules. Control over these properties can be achieved by chemical or physical modifications of the polysaccharide itself or the gels formed from alginate. The utility of these modified alginate gels as biomaterials has been demonstrated in a number of in vitro and in vivo studies.Micro-CT images of bone-like constructs that result from transplantation of osteoblasts on gels that degrade over a time frame of several months leading to improved bone formation. more...
- Published
- 2006
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35. Controlling alginate gel degradation utilizing partial oxidation and bimodal molecular weight distribution
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David J. Mooney, Hyunjoon Kong, and Tanyarut Boontheekul
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Materials science ,Compressive Strength ,Biocompatibility ,Alginates ,Cell Culture Techniques ,Biophysics ,Biocompatible Materials ,Bioengineering ,Cell Line ,Myoblasts ,Biomaterials ,Mice ,chemistry.chemical_compound ,Hydrolysis ,Glucuronic Acid ,Tensile Strength ,Materials Testing ,Polymer chemistry ,Cell Adhesion ,Animals ,Partial oxidation ,chemistry.chemical_classification ,Tissue Engineering ,Sodium periodate ,Hexuronic Acids ,Cell Differentiation ,Hydrogels ,Polymer ,Glucuronic acid ,Elasticity ,Molecular Weight ,chemistry ,Chemical engineering ,Mechanics of Materials ,Self-healing hydrogels ,Ceramics and Composites ,Molar mass distribution ,Calcium ,Oxidation-Reduction ,Porosity - Abstract
Degradability is often a critical property of materials utilized in tissue engineering. Although alginate, a naturally derived polysaccharide, is an attractive material due to its biocompatibility and ability to form hydrogels, its slow and uncontrollable degradation can be an undesirable feature. In this study, we characterized gels formed using a combination of partial oxidation of polymer chains and a bimodal molecular weight distribution of polymer. Specifically, alginates were partially oxidized to a theoretical extent of 1% with sodium periodate, which created acetal groups susceptible to hydrolysis. The ratio of low MW to high MW alginates used to form gels was also varied, while maintaining the gel forming ability of the polymer. The rate of degradation was found to be controlled by both the oxidation and the ratio of high to low MW alginates, as monitored by the reduction of mechanical properties and corresponding number of crosslinks, dry weight loss, and molecular weight decrease. It was subsequently examined whether these modifications would lead to reduced biocompatibility by culturing C2C12 myoblast on these gels. Myoblasts adhered, proliferated, and differentiated on the modified gels at a comparable rate as those cultured on the unmodified gels. Altogether, this data indicates these hydrogels exhibit tunable degradation rates and provide a powerful material system for tissue engineering. more...
- Published
- 2005
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36. Controlling Rigidity and Degradation of Alginate Hydrogels via Molecular Weight Distribution
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Darnell Kaigler, Hyunjoon Kong, Kiburn Kim, and David J. Mooney
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Polymers and Plastics ,Alginates ,Mineralogy ,Bone Marrow Cells ,Bioengineering ,Mice, SCID ,Uronic acid ,Biomaterials ,Mice ,chemistry.chemical_compound ,Materials Chemistry ,Animals ,Humans ,Bone Marrow Transplantation ,chemistry.chemical_classification ,Biomaterial ,Hydrogels ,Polymer ,Polyelectrolyte ,Rats ,Molecular Weight ,Transplantation ,chemistry ,Chemical engineering ,Covalent bond ,Self-healing hydrogels ,Molar mass distribution - Abstract
The mechanical rigidity and degradation rate of hydrogels utilized as cell transplantation vehicles have been regarded as critical factors in new tissue formation. However, conventional approaches to accelerate the degradation rate of gels deteriorate their function as a mechanical support in parallel. We hypothesized that adjusting the molecular weight distribution of polymers that are hydrolytically labile but capable of forming gels would allow one to alter the degradation rate of the gels over a broad range, while limiting the range of their elastic moduli (E). We investigated this hypothesis with binary alginate hydrogels formed from both ionically and covalently cross-linked partially oxidized (1% uronic acid residues), low [molecular weight (MW) approximately 60,000 g/mol] and high MW alginates (MW approximately 120,000 g/mol) in order to examine the utility of this approach with various cross-linking strategies. Increasing the fraction of low MW alginates to 0.50 maintained a value of E similar to that for the high MW alginate gels but led to faster degradation, irrespective of the cross-linking mode. This result was attributed to a faster separation between cross-linked domains upon chain breakages for the low MW alginates, coupled with their faster chain scission than the high MW alginates. The more rapidly degrading oxidized binary hydrogels facilitated the formation of new bone tissues from transplanted bone marrow stromal cells, as compared with the nonoxidized high MW hydrogels. The results of these studies will be useful for controlling the physical properties of a broad array of hydrogel-forming polymers. more...
- Published
- 2004
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37. Enzyme‐Induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypes
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Min Kyung Lee, Kathryn Michele Sullivan, Mei Hsiu Lai, Bumsoo Han, Hojeong Jeon, Nicholas E. Clay, Yen Wah Tong, Altug Ozcelikkale, Jiayu Leong, Youyun Liang, Hyunjoon Kong, and Max H. Rich
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,Polymers and Plastics ,Bioengineering ,Matrix metalloproteinase ,Matrix (biology) ,Radiation Tolerance ,Article ,Biomaterials ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Antigens, CD ,Elastic Modulus ,Materials Chemistry ,medicine ,Humans ,Radiosensitivity ,Composite material ,Cell Proliferation ,Chemistry ,Liver Neoplasms ,Cancer ,Hep G2 Cells ,Cadherins ,medicine.disease ,In vitro ,Extracellular Matrix ,Cell biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Matrix Metalloproteinase 1 ,Biotechnology - Abstract
The progression of cancer is often accompanied by changes in the mechanical properties of an extracellular matrix. However, limited efforts have been made to reproduce these biological events in vitro. To this end, this study demonstrates that matrix remodeling caused by matrix metalloproteinase (MMP)-1 regulates phenotypic activities and modulates radiosensitivity of cancer cells exclusively in a 3D matrix. In this study, hepatocarcinoma cells are cultured in a collagen-based gel tailored to present an elastic modulus of approximately 4.0 kPa. The subsequent exposure of the gel to MMP-1 decreases the elastic modulus from 4.0 to 0.5 kPa. In response to MMP-1, liver cancer cells undergo active proliferation, downregulation of E-cadherin and the loss of detoxification capacity. The resulting spheroids are more sensitive to radiation than the spheroids cultured in the stiffer gel not exposed to MMP-1. Overall, this study serves to better understand and control the effects of MMP-induced matrix remodeling. more...
- Published
- 2017
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38. Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators
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Lauren Grant, Hyunjoon Kong, Pablo Perez Pinera, Yongbeom Seo, Alexandra Palasz, Michael Gapinske, Caroline Cvetkovic, Howard Dabbous, Ritu Raman, and Rashid Bashir
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0301 basic medicine ,Biomedical Engineering ,Pharmaceutical Science ,Design elements and principles ,Healthy tissue ,02 engineering and technology ,Biology ,Optogenetics ,Article ,Cell Line ,Biomaterials ,Mice ,03 medical and health sciences ,medicine ,Animals ,Muscle, Skeletal ,Wound Healing ,Tissue Engineering ,Skeletal muscle ,Adaptive response ,021001 nanoscience & nanotechnology ,Biological materials ,030104 developmental biology ,Sense and respond ,medicine.anatomical_structure ,Stress, Mechanical ,0210 nano-technology ,Neuroscience ,Biomedical engineering - Abstract
A deeper understanding of biological materials and the design principles that govern them, combined with the enabling technology of 3D printing, has given rise to the idea of "building with biology." Using these materials and tools, bio-hybrid robots or bio-bots, which adaptively sense and respond to their environment, can be manufactured. Skeletal muscle bioactuators are developed to power these bio-bots, and an approach is presented to make them dynamically responsive to changing environmental loads and robustly resilient to induced damage. Specifically, since the predominant cause of skeletal muscle loss of function is mechanical damage, the underlying mechanisms of damage are investigated in vitro, and an in vivo inspired healing strategy is developed to counteract this damage. The protocol that is developed yields complete recovery of healthy tissue functionality within two days of damage, setting the stage for a more robust, resilient, and adaptive bioactuator technology than previously demonstrated. Understanding and exploiting the adaptive response behaviors inherent within biological systems in this manner is a crucial step forward in designing bio-hybrid machines that are broadly applicable to grand engineering challenges. more...
- Published
- 2017
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39. Matrix Rigidity-Modulated Cardiovascular Organoid Formation from Embryoid Bodies
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Kwanghyun Baek, Artem Shkumatov, and Hyunjoon Kong
- Subjects
Embryology ,Cellular differentiation ,Science ,Acrylic Resins ,Bioengineering ,Embryoid body ,Biology ,Matrix (biology) ,Cardiovascular System ,Cell Line ,Biomaterials ,Mice ,Animal Cells ,Culture Techniques ,Molecular Cell Biology ,Organoid ,Animals ,Regeneration ,Embryonic Stem Cells ,Embryoid Bodies ,Cell Proliferation ,Multidisciplinary ,Tissue Engineering ,Regeneration (biology) ,Stem Cells ,Myocardium ,Biology and Life Sciences ,Brain ,Cell Differentiation ,Hydrogels ,Anatomy ,Cell Biology ,Embryonic stem cell ,Immunohistochemistry ,Cell biology ,Organoids ,Self-healing hydrogels ,Microscopy, Electron, Scanning ,Medicine ,Collagen ,Stem cell ,Cellular Types ,Software ,Research Article ,Biotechnology ,Developmental Biology - Abstract
Stem cell clusters, such as embryoid bodies (EBs) derived from embryonic stem cells, are extensively studied for creation of multicellular clusters and complex functional tissues. It is common to control phenotypes of ES cells with varying molecular compounds; however, there is still a need to improve the controllability of cell differentiation, and thus, the quality of created tissue. This study demonstrates a simple but effective strategy to promote formation of vascularized cardiac muscle - like tissue in EBs and form contracting cardiovascular organoids by modulating the stiffness of a cell adherent hydrogel. Using collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we discovered that cellular organization in a form of vascularized cardiac muscle sheet was maximal on the gel with the stiffness similar to cardiac muscle. We envisage that the results of this study will greatly contribute to better understanding of emergent behavior of stem cells in developmental and regeneration process and will also expedite translation of EB studies to drug-screening device assembly and clinical treatments. more...
- Published
- 2014
40. Glacier moraine formation-mimicking colloidal particle assembly in microchanneled, bioactive hydrogel for guided vascular network construction
- Author
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Marni D. Boppart, Jonghwi Lee, Min Kyung Lee, Martha U. Gillette, Jae Hyun Jeong, Hyunjoon Kong, Artem Shkumatov, Rashid Bashir, and Max H. Rich
- Subjects
Vascular Endothelial Growth Factor A ,Geologic Sediments ,Materials science ,Bioactive molecules ,Biomedical Engineering ,Pharmaceutical Science ,Nanotechnology ,Biocompatible Materials ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Biomaterials ,Polylactic Acid-Polyglycolic Acid Copolymer ,Shear stress ,Animals ,Regeneration ,Geotechnical engineering ,Ice Cover ,Colloids ,Lactic Acid ,geography ,geography.geographical_feature_category ,Guided Tissue Regeneration ,Glacier ,Microspheres ,Mice, Inbred C57BL ,Freeze Drying ,Vascular network ,Moraine ,Colloidal particle ,Blood Vessels ,Chickens ,Polyglycolic Acid - Abstract
This study demonstrates that a new method to align microparticles releasing bioactive molecules in microchannels of a hydrogel allows the guiding of growth direction and spacing of vascular networks. more...
- Published
- 2014
41. Tailoring the dependency between rigidity and water uptake of a microfabricated hydrogel with the conformational rigidity of a polymer cross-linker
- Author
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Rashid Bashir, Jae Hyun Jeong, Vincent Chan, John J. Schmidt, Hyunjoon Kong, Mei Hsiu Lai, Chaenyung Cha, and Kwanghyun Baek
- Subjects
Polyacrylamide Hydrogel ,Flexibility (anatomy) ,Materials science ,Polymers and Plastics ,Alginates ,Acrylic Resins ,Bioengineering ,Biocompatible Materials ,Methacrylate ,Biomaterials ,Mice ,Elastic Modulus ,Polymer chemistry ,Materials Chemistry ,medicine ,Cell Adhesion ,Animals ,Composite material ,Acrylic resin ,Elastic modulus ,Fluorescent Dyes ,chemistry.chemical_classification ,Pyrenes ,Water ,Hydrogels ,Polymer ,medicine.anatomical_structure ,Cross-Linking Reagents ,chemistry ,visual_art ,Self-healing hydrogels ,visual_art.visual_art_medium ,NIH 3T3 Cells ,Methacrylates ,Microtechnology ,Swelling ,medicine.symptom ,Hydrophobic and Hydrophilic Interactions - Abstract
Many diverse applications utilize hydrogels as carriers, sensors, and actuators, and these applications rely on the refined control of physical properties of the hydrogel, such as elastic modulus and degree of swelling. Often, hydrogel properties are interdependent; for example, when elastic modulus is increased, degree of swelling is decreased. Controlling these inverse dependencies remains a major barrier for broader hydrogel applications. We hypothesized that polymer cross-linkers with varied chain flexibility would allow us to tune the inverse dependency between the elastic modulus and the degree of swelling of the hydrogels. We examined this hypothesis by using alginate and poly(acrylic acid) (PAA) modified with a controlled number of methacrylic groups as model inflexible and flexible cross-linkers, respectively. Interestingly, the polyacrylamide hydrogel cross-linked by the inflexible alginate methacrylates exhibited less dependency between the degree of swelling and the elastic modulus than the hydrogel cross-linked by flexible PAA methacrylates. This critical role of the cross-linker's inflexibility was related to the difference of the degree of hydrophobic association between polymer cross-linkers, as confirmed with pyrene probes added in pregel solutions. Furthermore, hydrogels cross-linked with alginate methacrylates could tune the projection area of adhered cells by solely altering elastic moduli. In contrast, gels cross-linked with PAA methacrylates failed to modulate the cellular adhesion morphology due to a lower, and smaller, elastic modulus range to be controlled. Overall, the results of this study will significantly advance the controllability of hydrogel properties and greatly enhance the performance of hydrogels in various biological applications. more...
- Published
- 2013
42. Stiffness-modulated water retention and neovascularization of dermal fibroblast-encapsulating collagen gel
- Author
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Hyunjoon Kong, Cathy Chu, Michelle Jang, Youyun Liang, Hae-Kwang Lee, Jin Woong Kim, Woonggyu Jung, Chaenyung Cha, Stephen A. Boppart, and Jae Hyun Jeong
- Subjects
Magnetic Resonance Spectroscopy ,Biomedical Engineering ,Neovascularization, Physiologic ,Bioengineering ,macromolecular substances ,Biochemistry ,Polyethylene Glycols ,Biomaterials ,Dermal fibroblast ,Neovascularization ,Glycosaminoglycan ,Prosthesis Implantation ,chemistry.chemical_compound ,Tissue engineering ,Dermis ,medicine ,Animals ,Humans ,Cell Shape ,Cell Proliferation ,Glycosaminoglycans ,Mechanical Phenomena ,Chemistry ,technology, industry, and agriculture ,Water ,Original Articles ,Fibroblasts ,Chorioallantoic membrane ,medicine.anatomical_structure ,Phenotype ,Self-healing hydrogels ,Biophysics ,Cattle ,Collagen ,medicine.symptom ,Ethylene glycol ,Chickens ,Gels ,Biomedical engineering - Abstract
There is increasing evidence that matrix stiffness modulates various phenotypic activities of cells surrounded by a three-dimensional (3D) matrix. These findings suggest that matrix stiffness can also regulate dermal fibroblasts activities to remodel, repair, and recreate skin dermis, but this has not yet been systematically demonstrated to date. This study examines the effects of matrix rigidity on the morphology, growth rates, and glycosaminoglycan (GAG) production of dermal fibroblasts cultured in collagen-based hydrogels with controlled elastic moduli. The elastic moduli (E) of collagen hydrogels were increased from 0.7 to 1.6 and 2.2 kPa by chemically cross-linking collagen fibrils with poly(ethylene glycol) disuccinimidylester. Increasing E of the hydrogel led to decreases in cellular spreading, nuclear aspect ratio, and growth rate. In contrast, the cellular GAG production level was elevated by increasing E from 0.7 to 1.6 kPa. The larger accumulation of GAG in the stiffer hydrogel led to increased water retention during exposure to air, as confirmed with magnetic resonance imaging. Additionally, in a chicken chorioallantoic membrane, a cell-encapsulating hydrogel with E of 1.6 kPa created dermis-like tissue with larger amount of GAG and density of blood vessels, while a cell-hydrogel construct with E of 0.7 kPa generated scar-like tissue. Overall, the results of this study will be highly useful for designing advanced tissue engineering scaffolds that can enhance the quality of a wide array of regenerated tissues including skin. more...
- Published
- 2013
43. Bioprinting: High-Resolution Projection Microstereolithography for Patterning of Neovasculature (Adv. Healthcare Mater. 5/2016)
- Author
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Basanta Bhaduri, Mustafa Mir, Ritu Raman, Gabriel Popescu, Min Kyung Lee, Rashid Bashir, Artem Shkumatov, and Hyunjoon Kong
- Subjects
Biomaterials ,Computer science ,law ,Biomedical Engineering ,Pharmaceutical Science ,High resolution ,Nanotechnology ,Projection (set theory) ,Stereolithography ,Biomedical engineering ,law.invention - Published
- 2016
- Full Text
- View/download PDF
44. Microfabrication of proangiogenic cell-laden alginate-g-pyrrole hydrogels
- Author
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Jae H. Jeong, Ross J. DeVolder, Andrew T. Zill, and Hyunjoon Kong
- Subjects
Vascular Endothelial Growth Factor A ,Materials science ,Angiogenesis ,Alginates ,Surface Properties ,medicine.medical_treatment ,Biophysics ,Neovascularization, Physiologic ,Bioengineering ,Biomaterials ,Neovascularization ,chemistry.chemical_compound ,Mice ,Glucuronic Acid ,medicine ,Cell Adhesion ,Animals ,Pyrroles ,Cell Proliferation ,Growth factor ,Hexuronic Acids ,Hydrogels ,Adhesion ,Fibroblasts ,Vascular endothelial growth factor ,Transplantation ,chemistry ,Mechanics of Materials ,Self-healing hydrogels ,Ceramics and Composites ,NIH 3T3 Cells ,Methacrylates ,Microtechnology ,Angiogenesis Inducing Agents ,medicine.symptom ,Wound healing ,Biomedical engineering - Abstract
Cells have been extensively studied for their uses in various therapies because of their capacities to produce therapeutic proteins and recreate new tissues. It has often been suggested that the efficacy of cell therapies can greatly be improved through the ability to localize and regulate cellular activities at a transplantation site; however, the technologies for this control are lacking. Therefore, this study reports a cell-Laden hydrogel patch engineered to support the proliferation and angiogenic growth factor expression of cells adhered to their surfaces, and to further promote neovascularization. Hydrogels consisting of alginate chemically linked with pyrrole units, termed alginate-g-pyrrole, were prepared through an oxidative cross-linking reaction between pyrrole units. Fibroblasts adhered to the alginate-g-pyrrole hydrogels, and exhibited increased proliferation and overall vascular endothelial growth factor (VEGF) expression, compared to those on pyrrole-free hydrogels. Furthermore, the alginate-g-pyrrole hydrogel surfaces were modified to present microposts, subsequently increasing the amount of pyrrole units on their surfaces. Cells adhered to the microfabricated gel surfaces exhibited increased proliferation and overall VEGF expression proportional to the density of the microposts. The resulting micropatterned alginate-g-pyrrole hydrogels exhibited increases in the size and density of mature blood vessels when implanted on chick chorioallantoic membranes (CAMs). The hydrogel system developed in this study will be broadly useful for improving the efficacy of a wide array of cell-based wound healing and tissue regenerative therapies. more...
- Published
- 2012
45. Ellipsoidal Polyaspartamide Polymersomes with Enhanced Cell-Targeting Ability
- Author
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Christopher Brockman, Hyunjoon Kong, Charles M. Schroeder, Jae Hyun Jeong, Mei Hsiu Lai, and Ross J. DeVolder
- Subjects
chemistry.chemical_classification ,Materials science ,Nanoparticle ,Nanotechnology ,Polymer ,Condensed Matter Physics ,Article ,Electronic, Optical and Magnetic Materials ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Polymersome ,PEG ratio ,Electrochemistry ,Biophysics ,Nanobiotechnology ,Self-assembly ,Cell adhesion ,Ethylene glycol - Abstract
Nano-sized polymersomes functionalized with peptides or proteins are being increasingly studied for targeted delivery of diagnostic and therapeutic molecules. Earlier computational studies have suggested that ellipsoidal nanoparticles, compared to spherical ones, display enhanced binding efficiency with target cells, but this has not yet been experimentally validated. We hypothesize that hydrophilic polymer chains coupled to vesicle-forming polymers would result in ellipsoidal polymersomes. In addition, ellipsoidal polymersomes modified with cell adhesion peptides bind with target cells more actively than spherical ones. We examine this hypothesis by substituting polyaspartamide with octadecyl chains and varying numbers of poly(ethylene glycol) (PEG) chains. Increasing the degree of substitution of PEG from 0.5 to 1.0 mol% drives the polymer to self-assemble into an ellipsoidal polymersome with an aspect ratio of 2.1. Further modification of these ellipsoidal polymersomes with peptides containing an Arg-Gly-Asp sequence (RGD peptides) lead to a significant increase in the rate of association and decrease in the rate of dissociation with a substrate coated with αvβ3 integrins. In addition, in a circulation-mimicking flow, the ellipsoidal polymersomes linked with RGD peptides adhere to target tissues more favorably than their spherical equivalents do. Overall, the results of this study will greatly serve to improve the efficiency of targeted delivery of a wide array of polymersomes loaded with various biomedical modalities. more...
- Published
- 2012
46. Modulating the rigidity and mineralization of collagen gels using poly(lactic-co-glycolic acid) microparticles
- Author
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Ross J. DeVolder, Il Won Kim, Eun Suk Kim, and Hyunjoon Kong
- Subjects
Simulated body fluid ,Biomedical Engineering ,Bioengineering ,Bone healing ,macromolecular substances ,Biochemistry ,Apatite ,Permeability ,Biomaterials ,chemistry.chemical_compound ,Mice ,Polylactic Acid-Polyglycolic Acid Copolymer ,Osteogenesis ,Materials Testing ,Animals ,Lactic Acid ,Glycolic acid ,Minerals ,Mesenchymal stem cell ,technology, industry, and agriculture ,Cell Differentiation ,Hydrogels ,Mesenchymal Stem Cells ,Original Articles ,Microspheres ,Lactic acid ,PLGA ,chemistry ,visual_art ,Self-healing hydrogels ,visual_art.visual_art_medium ,Microscopy, Electron, Scanning ,Collagen ,Polyglycolic Acid ,Biomedical engineering ,Fluorescence Recovery After Photobleaching - Abstract
Extensive efforts have been made to prepare osteoconductive collagen gels for the regeneration of normal bone and the pathological examination of diseased bone; however, collagen gels are often plagued by limited controllability of their rigidity and mineral deposition. This study reports a simple but efficient strategy that tunes the mechanical properties of, and apatite formation in, collagen gels by incorporating hydrolyzable poly(lactic-co-glycolic acid) (PLGA) microparticles within the gels. The PLGA microparticles are associated with the collagen fibrils and increased both the gel's elasticity and rigidity while minimally influencing its permeability. As compared with pure collagen gels, the PLGA microparticle-filled collagen gels, termed PLGA-Col hydrogels, significantly enhanced the deposition of apatite-like minerals within the gels when incubated in simulated body fluid or encapsulated with mesenchymal stem cells (MSCs) undergoing osteogenic differentiation. Finally, PLGA-Col hydrogels mineralized by differentiated MSCs led to an enhanced formation of bone-like tissues within the hydrogels. Overall, the PLGA-Col hydrogel system developed in this study will serve to improve the quality of osteoconductive matrices for both fundamental and clinical studies that are relevant to bone repair, regeneration, and pathogenesis. more...
- Published
- 2012
47. The interplay between cell adhesion cues and curvature of cell adherent alginate microgels in multipotent stem cell culture
- Author
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John J. Schmidt, Jae Hyun Jeong, and Hyunjoon Kong
- Subjects
Alginates ,Cell ,Biomedical Engineering ,Bioengineering ,Biochemistry ,Biomaterials ,Glucuronic Acid ,Osteogenesis ,medicine ,Cell Adhesion ,Cell adhesion ,Oligopeptide ,Tissue Scaffolds ,Chemistry ,Cell growth ,Hexuronic Acids ,Multipotent Stem Cells ,Mesenchymal stem cell ,Microcarrier ,Cell Differentiation ,Original Articles ,Phenotype ,Cell biology ,medicine.anatomical_structure ,Multipotent Stem Cell ,Stress, Mechanical ,Oligopeptides - Abstract
Cell-adherent microcarriers are increasingly used to expand multipotent stem cells on a large scale for therapeutic applications. However, the role of the microcarrier properties and geometry on the phenotypic activities of multipotent cells has not been well studied. This study presents a significant interplay of the number of cell adhesion sites and the curvature of the microcarrier in regulating cell growth and differentiation by culturing mesenchymal stem cells on alginate microgels chemically linked with oligopeptides containing the Arg-Gly-Asp (RGD) sequence. Interestingly, the cell growth rate and osteogenic differentiation level were increased with the RGD peptide density. At a given RGD peptide density, the cell growth rate was inversely related to the microgel diameter, whereas the osteogenic differentiation level was minimally influenced. The dependency of the cell growth rate on the microgel diameter was related to changes in shear stresses acting on cells according to simulation. Overall, this study identifies material variables key to regulating cellular activities on microcarriers, and these findings will be useful to designing a broad array of bioactive microcarriers. more...
- Published
- 2011
48. A cell-instructive hydrogel to regulate malignancy of 3D tumor spheroids with matrix rigidity
- Author
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Chaenyung Cha, Youyun Liang, Fei Wang, Yen Wah Tong, Ross J. DeVolder, Hyunjoon Kong, and Jae Hyun Jeong
- Subjects
Cellular pathology ,Materials science ,Cell ,Biophysics ,Bioengineering ,Malignancy ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Permeability ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Neoplasms ,Spheroids, Cellular ,medicine ,Humans ,Cell Proliferation ,Neovascularization, Pathologic ,Spheroid ,Hep G2 Cells ,medicine.disease ,Extracellular Matrix ,medicine.anatomical_structure ,Phenotype ,chemistry ,Mechanics of Materials ,Cancer cell ,Self-healing hydrogels ,Ceramics and Composites ,Collagen ,Ethylene glycol ,Intracellular ,Biomedical engineering - Abstract
Three dimensional (3D) tumor spheroid models are becoming important biomedical tools for both fundamental and applied cancer studies, but current models do not account for different levels of cancer malignancy. Several studies have reported that the mechanical rigidity of a hydrogel plays a significant role in regulating the phenotypes of cancer cells adhered to the gel surface. This finding suggests that matrix rigidity should also modulate the malignancy of 3D tumor spheroids. However, the role of matrix stiffness is often confounded by concurrent changes in 3D matrix permeability. This study reports an advanced strategy to assemble 3D liver tumor spheroids with controlled intercellular organization, phenotypes, and angiogenic activities using hydrogels with controlled stiffness and minimal differences in molecular diffusivity. The elastic moduli of cell-encapsulated collagen gels were increased by stiffening interconnected collagen fibers with varied amounts of poly(ethylene glycol) di-(succinic acid N-hydroxysuccinimidyl ester). Interestingly, hepatocellular carcinoma cells encapsulated in a fat-like, softer hydrogel formed malignant cancer spheroids, while cells cultured in a liver-like, stiffer gel formed compact hepatoids with suppressed malignancy. Overall, both the hydrogel and the 3D tumor spheroids developed in this study will be greatly useful to better understand and regulate the emergent behaviors of various cancer cells. more...
- Published
- 2011
49. Tuning the dependency between stiffness and permeability of a cell encapsulating hydrogel with hydrophilic pendant chains
- Author
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Hyunjoon Kong, Chaenyung Cha, Jongwon Shim, and Jae Hyun Jeong
- Subjects
Vascular Endothelial Growth Factor A ,Materials science ,Cell Survival ,Biomedical Engineering ,macromolecular substances ,Matrix (biology) ,complex mixtures ,Biochemistry ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Permeability ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Mice ,Elastic Modulus ,PEG ratio ,Animals ,Composite material ,Cell encapsulation ,Molecular Biology ,Elastic modulus ,Cell Proliferation ,Mechanical Phenomena ,chemistry.chemical_classification ,technology, industry, and agriculture ,General Medicine ,Polymer ,Cells, Immobilized ,Fibroblasts ,chemistry ,Permeability (electromagnetism) ,Self-healing hydrogels ,Biophysics ,NIH 3T3 Cells ,Ethylene glycol ,Hydrophobic and Hydrophilic Interactions ,Biotechnology ,Fluorescence Recovery After Photobleaching - Abstract
The mechanical stiffness of a hydrogel plays a significant role in regulating the phenotype of cells that adhere to its surface. However, the effect of hydrogel stiffness on cells cultured within its matrix is not well understood, because of the intrinsic inverse dependency between the permeability and stiffness of hydrogels. This study therefore presents an advanced biomaterial design strategy to decrease the inverse dependency between permeability and stiffness of a cell encapsulating hydrogel. Hydrogels were made by cross-linking poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) monoacrylate (PEGMA), with PEGMA acting as a pendant polymer chain. Increasing the mass fraction of PEGMA while keeping the total polymer concentration constant led to a decrease in the elastic modulus (E) of the hydrogel, but caused a minimal increase in the swelling ratio (Q). The size and hydrophobicity of the end groups of pendant PEG chains further fine tuned the dependency between Q and E of the hydrogel. Pure PEGDA hydrogels with varying molecular weights, which show the same range of E but a much greater range of Q, were used as a control. Fibroblasts encapsulated in PEGDA-PEGMA hydrogels displayed more significant biphasic dependencies of cell viability and vascular endothelial growth factor (VEGF) expression on E than those encapsulated in pure PEGDA hydrogels, which were greatly influenced by Q. Overall, the hydrogel design strategy presented in this study will be highly useful to better regulate the phenotype and ultimately improve the therapeutic efficacy of a wide array of cells used in various biology studies and clinical settings. more...
- Published
- 2011
50. Tuning the non-equilibrium state of a drug-encapsulated poly(ethylene glycol) hydrogel for stem and progenitor cell mobilization
- Author
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Richie E. Kohman, Kyle B. Textor, Youyun Liang, Yen Wah Tong, Bao Zhong Zhang, Ross J. DeVolder, Lawrence B. Schook, Tor W. Jensen, Chaenyung Cha, Hyunjoon Kong, Lauretta A. Rund, and Edward J. Roy
- Subjects
Materials science ,Magnetic Resonance Spectroscopy ,Biophysics ,Bioengineering ,macromolecular substances ,Chick Embryo ,Article ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Polyethylene Glycols ,Biomaterials ,chemistry.chemical_compound ,Mice ,Drug Delivery Systems ,medicine ,Animals ,Progenitor cell ,Elastic modulus ,Stem Cells ,technology, industry, and agriculture ,Mice, Inbred C57BL ,chemistry ,Mechanics of Materials ,Self-healing hydrogels ,Drug delivery ,Receptors, Granulocyte Colony-Stimulating Factor ,Ceramics and Composites ,Degradation (geology) ,Female ,Swelling ,medicine.symptom ,Stem cell ,Ethylene glycol ,Chickens ,Biomedical engineering - Abstract
Injectable and biodegradable hydrogels have been increasingly studied for sustained drug delivery in various molecular therapies. However, it remains a challenge to attain desired delivery rate at injection sites due to local tissue pressures exerted on the soft hydrogels. Furthermore, there is often limited controllability of stiffness and degradation rates, which are key factors required for achieving desired drug release rate and therapeutic efficacy. This study presents a stiff and metastable poly(ethylene glycol) diacrylate (PEGDA)-poly(ethylene imine) (PEI) hydrogel which exhibits an elastic modulus equivalent to bulk plastic materials, and controllable degradation rate independent of its initial elastic modulus. Such unique stiffness was attained from the highly branched architecture of PEI, and the decoupled controllability of degradation rate was achieved by tuning the non-equilibrium swelling of the hydrogel. Furthermore, a single intramuscular administration of granulocyte colony stimulating factor (GCSF)-encapsulated PEGDA-PEI hydrogel extended the mobilization of mononuclear cells to four days. A larger yield of expanded CD34+ and CD31+ endothelial progenitor cells (EPCs) was also obtained as compared to the daily bolus administration. Overall, the hydrogel created in this study will be useful for the controlled and sustained delivery of a wide array of drug molecules. more...
- Published
- 2010
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