23 results on '"Kaplan, David"'
Search Results
2. 3D freeform printing of silk fibroin.
- Author
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Rodriguez, Maria J., Dixon, Thomas A., Cohen, Eliad, Huang, Wenwen, Omenetto, Fiorenzo G., and Kaplan, David L.
- Subjects
RAPID prototyping ,THREE-dimensional printing ,SILK fibroin ,CROSSLINKING (Polymerization) ,BIOPRINTING ,EQUIPMENT & supplies - Abstract
Freeform fabrication has emerged as a key direction in printing biologically-relevant materials and structures. With this emerging technology, complex structures with microscale resolution can be created in arbitrary geometries and without the limitations found in traditional bottom-up or top-down additive manufacturing methods. Recent advances in freeform printing have used the physical properties of microparticle-based granular gels as a medium for the submerged extrusion of bioinks. However, most of these techniques require post-processing or crosslinking for the removal of the printed structures (Miller et al., 2015; Jin et al., 2016) [1,2] . In this communication, we introduce a novel method for the one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite) and polyethylene glycol (PEG). Silk fibroin has been used as a biopolymer for bioprinting in several contexts, but chemical or enzymatic additives or bulking agents are needed to stabilize 3D structures. Our method requires no post-processing of printed structures and allows for in situ physical crosslinking of pure aqueous silk fibroin into arbitrary geometries produced through freeform 3D printing. Statement of Significance 3D bioprinting has emerged as a technology that can produce biologically relevant structures in defined geometries with microscale resolution. Techniques for fabrication of free-standing structures by printing into granular gel media has been demonstrated previously, however, these methods require crosslinking agents and post-processing steps on printed structures. Our method utilizes one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite), with no need for additional crosslinking compounds or post processing of the material. This new method allows for in situ physical crosslinking of pure aqueous silk fibroin into defined geometries produced through freeform 3D printing. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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3. High‐Strength, Durable All‐Silk Fibroin Hydrogels with Versatile Processability toward Multifunctional Applications.
- Author
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Zhu, Zhenghua, Ling, Shengjie, Yeo, Jingjie, Zhao, Siwei, Tozzi, Lorenzo, Buehler, Markus J., Omenetto, Fiorenzo, Li, Chunmei, and Kaplan, David L.
- Subjects
HYDROGELS ,SILK fibroin ,BIOSENSORS ,LASER beam cutting ,HYDROGELS in medicine ,ANALYTICAL chemistry - Abstract
Abstract: Hydrogels are the focus of extensive research due to their potential use in fields including biomedical, pharmaceutical, biosensors, and cosmetics. However, the general weak mechanical properties of hydrogels limit their utility. Here, pristine silk fibroin (SF) hydrogels with excellent mechanical properties are generated via a binary‐solvent‐induced conformation transition (BSICT) strategy. In this method, the conformational transition of SF is regulated by moderate binary solvent diffusion and SF/solvent interactions. β‐sheet formation serves as the physical crosslinks that connect disparate protein chains to form continuous 3D hydrogel networks, avoiding complex chemical and/or physical treatments. The Young's modulus of these new BSICT–SF hydrogels can reach up to 6.5 ± 0.2 MPa, tens to hundreds of times higher than that of conventional hydrogels (0.01–0.1 MPa). These new materials fill the “empty soft materials' space” in the elastic modulus/strain Ashby plot. More remarkably, the BSICT–SF hydrogels can be processed into different constructions through different polymer and/or metal‐based processing techniques, such as molding, laser cutting, and machining. Thus, these new hydrogel systems exhibit potential utility in many biomedical and engineering fields. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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4. Silk scaffolds with tunable mechanical capability for cell differentiation.
- Author
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Bai, Shumeng, Han, Hongyan, Huang, Xiaowei, Xu, Weian, Kaplan, David L., Zhu, Hesun, and Lu, Qiang
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TISSUE scaffolds ,BIOMATERIALS ,MECHANICAL behavior of materials ,CELL differentiation ,MESENCHYMAL stem cells ,TISSUE engineering - Abstract
Bombyx mori silk fibroin is a promising biomaterial for tissue regeneration and is usually considered an “inert” material with respect to actively regulating cell differentiation due to few specific cell signaling peptide domains in the primary sequence and the generally stiffer mechanical properties due to crystalline content formed in processing. In the present study, silk fibroin porous 3D scaffolds with nanostructures and tunable stiffness were generated via a silk fibroin nanofiber-assisted lyophilization process. The silk fibroin nanofibers with high β-sheet content were added into the silk fibroin solutions to modulate the self-assembly, and to directly induce water-insoluble scaffold formation after lyophilization. Unlike previously reported silk fibroin scaffold formation processes, these new scaffolds had lower overall β-sheet content and softer mechanical properties for improved cell compatibility. The scaffold stiffness could be further tuned to match soft tissue mechanical properties, which resulted in different differentiation outcomes with rat bone marrow-derived mesenchymal stem cells toward myogenic and endothelial cells, respectively. Therefore, these silk fibroin scaffolds regulate cell differentiation outcomes due to their mechanical features. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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5. Silk–tropoelastin protein films for nerve guidance.
- Author
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White, James D., Wang, Siran, Weiss, Anthony S., and Kaplan, David L.
- Subjects
TROPOELASTIN ,SILK fibroin ,BIOMATERIALS ,NEURONS ,LYSINE - Abstract
Peripheral nerve regeneration may be enhanced through the use of biodegradable thin film biomaterials as highly tuned inner nerve conduit liners. Dorsal root ganglion neuron and Schwann cell responses were studied on protein films comprising silk fibroin blended with recombinant human tropoelastin protein. Tropoelastin significantly improved neurite extension and enhanced Schwann cell process length and cell area, while the silk provided a robust biomaterial template. Silk–tropoelastin blends afforded a 2.4-fold increase in neurite extension, when compared to silk films coated with poly- d -lysine. When patterned by drying on grooved polydimethylsiloxane (3.5 μm groove width, 0.5 μm groove depth), these protein blends induced both neurite and Schwann cell process alignment. Neurons were functional as assessed using patch-clamping, and displayed action potentials similar to those cultured on poly(lysine)-coated glass. Taken together, silk–tropoelastin films offer useful biomaterial interfacial platforms for nerve cell control, which can be considered for neurite guidance, disease models for neuropathies and surgical peripheral nerve repairs. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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6. Regeneration of high-quality silk fibroin fiber by wet spinning from CaCl2–formic acid solvent.
- Author
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Zhang, Feng, Lu, Qiang, Yue, Xiaoxiao, Zuo, Baoqi, Qin, Mingde, Li, Fang, Kaplan, David L., and Zhang, Xueguang
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SILK fibroin ,FORMIC acid ,CALCIUM chloride ,NANOCRYSTALS ,BIOMATERIALS ,MECHANICAL behavior of materials - Abstract
Silks spun by silkworms and spiders feature outstanding mechanical properties despite being spun under benign conditions. The superior physical properties of silk are closely related to its complicated hierarchical structures constructed from nanoscale building blocks, such as nanocrystals and nanofibrils. Here, we report a novel silk dissolution behavior, which preserved nanofibrils in CaCl 2 –formic acid solution, that enables spinning of high-quality fibers with a hierarchical structure. This process is characterized by simplicity, high efficiency, low cost, environmental compatibility and large-scale industrialization potential, as well as having utility and potential for the recycling of silk waste and the production of silk-based functional materials. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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7. Complementary Effects of Two Growth Factors in Multifunctionalized Silk Nanofibers for Nerve Reconstruction.
- Author
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Dinis, Tony M., Vidal, Guillaume, Jose, Rodrigo R., Vigneron, Pascale, Bresson, Damien, Fitzpatrick, Vincent, Marin, Frédéric, Kaplan, David L., and Egles, Christophe
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PERIPHERAL nervous system ,SILK fibroin ,NANOFIBERS ,NERVE growth factor ,ELECTROSPINNING ,NEURONS - Abstract
With the aim of forming bioactive guides for peripheral nerve regeneration, silk fibroin was electrospun to obtain aligned nanofibers. These fibers were functionalized by incorporating Nerve Growth Factor (NGF) and Ciliary NeuroTrophic Factor (CNTF) during electrospinning. PC12 cells grown on the fibers confirmed the bioavailability and bioactivity of the NGF, which was not significantly released from the fibers. Primary neurons from rat dorsal root ganglia (DRGs) were grown on the nanofibers and anchored to the fibers and grew in a directional fashion based on the fiber orientation, and as confirmed by growth cone morphology. These biofunctionalized nanofibers led to a 3-fold increase in neurite length at their contact, which was likely due to the NGF. Glial cell growth, alignment and migration were stimulated by the CNTF in the functionalized nanofibers. Organotypic culture of rat fetal DRGs confirmed the complementary effect of both growth factors in multifunctionalized nanofibers, which allowed glial cell migration, alignment and parallel axonal growth in structures resembling the ‘bands of Bungner’ found in situ. Graftable multi-channel conduits based on biofunctionalized aligned silk nanofibers were developed as an organized 3D scaffold. Our bioactive silk tubes thus represent new options for a biological and biocompatible nerve guidance conduit. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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8. Encapsulation of oil in silk fibroin biomaterials.
- Author
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Pritchard, Eleanor M., Normand, Valery, Hu, Xiao, Budijono, Stephanie, Benczédi, Daniel, Omenetto, Fiorenzo, and Kaplan, David L.
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SILK fibroin ,BIOMATERIALS ,AQUEOUS solutions ,MOLECULAR self-assembly ,MICROENCAPSULATION ,MICELLES ,BIOENGINEERING - Abstract
ABSTRACT Microencapsulation is becoming increasingly important in the food, cosmetics, and medicinal industries due to its potential for stabilization and delivery of volatile and delicate compounds. Novel food-safe techniques for encapsulating oil in silk biomaterials using emulsion-based processes that exploit silk's unique properties (including amphiphilicity, biocompatibility, aqueous and ambient processing, and tunable physical crosslinking behavior) are described. The sonication-induced self-assembly of silk previously applied to hydrogel fabrication replaced the use of the thermal or chemical suspension crosslinking traditionally used to stabilize the aqueous protein phase in emulsions. Stable, physically crosslinked silk micro- and macro-particles loaded with oil or water-soluble dye were produced by aliquoting sonicated silk solutions into an oil bath. Oil micro-droplets emulsified in aqueous silk solutions did not impede the self-assembly of silk into films or hydrogel networks. In O/W/O emulsions, particle morphology and silk permeability to a model lipophilic dye in the interior phase were controllable via processing. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39990. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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9. Acellular Bi-Layer Silk Fibroin Scaffolds Support Tissue Regeneration in a Rabbit Model of Onlay Urethroplasty.
- Author
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Chung, Yeun Goo, Tu, Duong, Franck, Debra, Gil, Eun Seok, Algarrahi, Khalid, Adam, Rosalyn M., Kaplan, David L., Estrada Jr., Carlos R., and Mauney, Joshua R.
- Subjects
SILK fibroin ,BISMUTH ,URETHROPLASTY ,REGENERATION (Biology) ,LABORATORY rabbits ,BIOMATERIALS - Abstract
Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a rabbit model of urethra repair. A bi-layer silk fibroin matrix was fabricated by a solvent-casting/salt leaching process in combination with silk fibroin film casting to generate porous foams buttressed by homogeneous silk fibroin films. Ventral onlay urethroplasty was performed with silk fibroin grafts (Group 1, N = 4) (Width×Length, 1×2 cm
2 ) in adult male rabbits for 3 m of implantation. Parallel control groups consisted of animals receiving small intestinal submucosa (SIS) implants (Group 2, N = 4) or urethrotomy alone (Group 3, N = 3). Animals in all groups exhibited 100% survival prior to scheduled euthanasia and achieved voluntary voiding following 7 d of initial catheterization. Retrograde urethrography of each implant group at 3 m post-op revealed wide urethral calibers and preservation of organ continuity similar to pre-operative and urethrotomy controls with no evidence of contrast extravasation, strictures, fistulas, or stone formation. Histological (hematoxylin and eosin and Masson's trichrome), immunohistochemical, and histomorphometric analyses demonstrated that both silk fibroin and SIS scaffolds promoted similar extents of smooth muscle and epithelial tissue regeneration throughout the original defect sites with prominent contractile protein (α-smooth muscle actin and SM22α) and cytokeratin expression, respectively. De novo innervation and vascularization were also evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Following 3 m post-op, minimal acute inflammatory reactions were elicited by silk fibroin scaffolds characterized by the presence of eosinophil granulocytes while SIS matrices promoted chronic inflammatory responses indicated by mobilization of mononuclear cell infiltrates. The results of this study demonstrate that bi-layer silk fibroin scaffolds represent promising biomaterials for onlay urethroplasty, capable of promoting similar degrees of tissue regeneration in comparison to conventional SIS scaffolds, but with reduced immunogenicity. [ABSTRACT FROM AUTHOR]- Published
- 2014
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10. Antibiotic-Releasing Silk Biomaterials for Infection Prevention and Treatment.
- Author
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Pritchard, Eleanor M., Valentin, Thomas, Panilaitis, Bruce, Omenetto, Fiorenzo, and Kaplan, David L.
- Abstract
Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled-release polymer implants have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery, including biocompatibility, tunable biodegradation, stabilizing effects, water-based processing, and diverse material formats. The functional release of antibiotics spanning a range of chemical properties from different material formats of silk (films, microspheres, hydrogels, coatings) is reported. The release of penicillin and ampicillin from bulk-loaded silk films, drug-loaded silk microspheres suspended in silk hydrogels and bulk-loaded silk hydrogels is investigated and the in vivo efficacy of the ampicillin-releasing silk hydrogels is demonstrated in a murine infected-wound model. Silk sponges with nanofilm coatings are loaded with gentamicin and cefazolin, and release is sustained for 5 and 3 days, respectively. The capability of silk antibiotic carriers to sequester, stabilize, and then release bioactive antibiotics represents a major advantage over implants and pumps based on liquid drug reservoirs, where instability at room or body temperature is limiting. The present studies demonstrate that silk biomaterials represent a novel, customizable antibiotic platform for focal delivery of antibiotics using a range of material formats (injectable to implantable). [ABSTRACT FROM AUTHOR]
- Published
- 2013
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11. Sodium dodecyl sulfate-induced rapid gelation of silk fibroin.
- Author
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Wu, Xilong, Hou, Jing, Li, Mingzhong, Wang, Jiangnan, Kaplan, David L., and Lu, Shenzhou
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SODIUM dodecyl sulfate ,GELATION ,SILK fibroin ,HYDROGELS ,BIOMATERIALS ,SURFACE active agents ,NANOPARTICLES - Abstract
Abstract: The in situ formation of injectable silk fibroin (SF) hydrogels have potential advantages over various other biomaterials due to the minimal invasiveness during application. Biomaterials need to gel rapidly under physiological conditions after injection. In the current paper, a novel way to accelerate SF gelation using an anionic surfactant, sodium dodecyl sulfate (SDS), as a gelling agent is reported. The mechanism of SDS-induced rapid gelation was determined. At low surfactant concentrations, hydrophobic interactions among the SF chains played a dominant role in the association, leading to decreased gelation time. At higher concentrations of surfactant, electrostatic repulsive forces among micellar aggregates gradually became dominant and gelation was hindered. Gel formation involves the connection of clusters formed by the accumulation of nanoparticles. This process is accompanied by the rapid formation of β-sheet structures due to hydrophobic and electrostatic interactions. It is expected that the silk hydrogel with short gelation time will be used as an injectable hydrogel in drug delivery or cartilage tissue engineering. [Copyright &y& Elsevier]
- Published
- 2012
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12. Corrigendum to “NF-κB signaling is key in the wound healing processes of silk fibroin” [Acta Biomater. 67 (2018), 183–195].
- Author
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Park, Ye Ri, Sultan, Md. Tipu, Park, Hyun Jung, Lee, Jung Min, Ju, Hyung Woo, Lee, Ok Joo, Lee, Dong Jin, Kaplan, David L., and Park, Chan Hum
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SILK fibroin ,BIOMATERIALS ,BIOLOGICAL specimen analysis ,HEAD & neck cancer ,OTOLARYNGOLOGY ,MEDICINE - Published
- 2018
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13. Modulation of vincristine and doxorubicin binding and release from silk films.
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Coburn, Jeannine M., Na, Elim, and Kaplan, David L.
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VINCRISTINE , *DOXORUBICIN , *PHOTOGRAPHIC film , *TYROSINE , *ONCOLOGY research - Abstract
Sustained release drug delivery systems remain a major clinical need for small molecule therapeutics in oncology. Here, mechanisms of small molecule interactions with silk protein films were studied with cationic oncology drugs, vincristine and doxorubicin, with a focus on hydrophobicity (non-ionic surfactant) and charge (pH and ionic strength). Interactions were primarily driven by charge interactions between the positively charged drugs and the negatively charged groups within the silk films. Exploiting chemical modifications of silk further modulated the drug interactions in a controlled fashion. Increasing anionic side groups via carboxylate- and sulfonate-modifications of tyrosine side chains in the silk protein using diazonium coupling chemistry, increased drug binding and altered drug release. The effects of silk film protein crystallinity, beta sheet content, on drug binding and release were also explored. Lower crystallinity supported more rapid drug binding when compared to higher crystalline silk films. The drug release kinetics were governed by the protonation state of vincristine and doxorubicin and were tunable based on silk crystallinity and chemistry. These studies depict an approach to characterize small molecule–silk protein interactions and methods to tune drug binding and release kinetics from this protein delivery matrix. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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14. Modification of silk fibroin using diazonium coupling chemistry and the effects on hMSC proliferation and differentiation
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Murphy, Amanda R., John, Peter St., and Kaplan, David L.
- Subjects
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AMINO acids , *AROMATIC amines , *SPECTRUM analysis , *FOURIER transform infrared spectroscopy - Abstract
Abstract: A simple chemical modification method using diazonium coupling chemistry was developed to tailor the structure and hydrophilicity of silk fibroin protein. The extent of modification using several aniline derivatives was characterized using UV–vis and 1H NMR spectroscopies, and the resulting protein structure was analyzed with ATR-FTIR spectroscopy. Introduction of hydrophobic functional groups facilitated rapid conversion of the protein from a random coil to a β-sheet structure, while addition of hydrophilic groups inhibited this process. hMSCs were grown on these modified silks to assess the biocompatibility of these materials. The hydrophilicity of the silk derivatives was found to affect the growth rate and morphology, but hMSCs were able to attach, proliferate and differentiate into an osteogenic lineage on all of the silk derivatives. [Copyright &y& Elsevier]
- Published
- 2008
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15. In Situ 3D Printing: Opportunities with Silk Inks.
- Author
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Agostinacchio, Francesca, Mu, Xuan, Dirè, Sandra, Motta, Antonella, and Kaplan, David L.
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THREE-dimensional printing , *SILK fibroin , *SILK , *PRINTMAKING , *DESIGN techniques , *BIOMATERIALS - Abstract
In situ 3D printing is an emerging technique designed for patient-specific needs and performed directly in the patient's tissues in the operating room. While this technology has progressed rapidly, several improvements are needed to push it forward for widespread utility, including ink formulations and optimization for in situ context. Silk fibroin inks emerge as a viable option due to the diverse range of formulations, aqueous processability, robust and tunable mechanical properties, and self-assembly via biophysical adsorption to avoid exogenous chemical or photochemical sensitizer additives, among other features. In this review, we focus on this new frontier of 3D in situ printing for tissue regeneration, where silk is proposed as candidate biomaterial ink due to the unique and useful properties of this protein polymer. In vitro 3D printing techniques have challenges that limit their clinical translation, including multistep processes, mismatches with patient-specific defects, risk of contamination, and postprocessing manipulation requirements. In situ 3D printing, the next frontier for 3D printing, aims to fabricate new tissues and organs in vivo , in the surgical setting, directly in the patient. Inks remain a challenge for this transition to in situ 3D printing, requiring fast gelation, high shape fidelity, minimal if any postprocessing, robust mechanical properties tunable to the target tissue, and biocompatibility. Versatile and appropriate inks, such as those developed from silk fibroin, offer a foundation for this translation, based on their unique amphiphilic structure, versatility in physical crosslinking, mechanical properties, biocompatibility, and tunable degradation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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16. Silk fibroin for skin injury repair: Where do things stand?
- Author
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Gholipourmalekabadi, Mazaher, Sapru, Sunaina, Samadikuchaksaraei, Ali, Reis, Rui L., Kaplan, David L., and Kundu, Subhas C.
- Subjects
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SILK fibroin , *SKIN injuries , *SPARE parts , *TISSUE mechanics , *REGENERATIVE medicine , *TISSUE engineering - Abstract
Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed. Silk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications. Silkworm silk fibroin is a well-established natural protein in the realm of biomaterials with an array of matrices in its repository. These range from primary bio coating to state of the art, bioprinting en route for creating an advanced graft for diversified biomedical applications. Augmenting these matrices by incorporating functional traits like delivery of bioactive molecules/compounds (growth factor, drug, antibiotic, gene or cell) or conductivity make them smart matrices for skin tissue regeneration and skin repair. Unlabelled Image [ABSTRACT FROM AUTHOR]
- Published
- 2020
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17. Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations.
- Author
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Yavuz, Burcin, Zeki, Jasmine, Taylor, Jordan, Harrington, Kristin, Coburn, Jeannine M., Ikegaki, Naohiko, Kaplan, David L., and Chiu, Bill
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THERAPEUTICS , *CISPLATIN , *RESERVOIRS , *NEUROBLASTOMA , *ALKYLATING agents , *SILK fibroin - Abstract
Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug chemotherapy. Local, perioperative delivery of chemotherapeutics is a promising treatment method for solid tumors that require surgical removal. In this study, we have aimed to develop a controlled-release implant system to deliver cisplatin in tumor or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used to encapsulate different doses of cisplatin in a reservoir system. The physical integrity of the reservoirs was characterized by evaluating the crystalline structure of silk secondary structure using FTIR spectroscopy. The in vitro release of cisplatin was evaluated in phosphate-buffered saline at 37°C, and the reservoirs were able to release the drug up to 30 days. The cytotoxicity of cisplatin and cisplatin reservoirs were tested on KELLY cells. Cytotoxicity data showed 3.2 μg/mL cisplatin was required to kill 50% of the cell population, and the released cisplatin from the silk reservoirs showed significant cytotoxicity up to 21 days. Intratumoral implantation of silk reservoirs into an orthotopic neuroblastoma mouse model decreased tumor growth significantly when compared with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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18. Enzymatically crosslinked silk-hyaluronic acid hydrogels.
- Author
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Raia, Nicole R., Partlow, Benjamin P., McGill, Meghan, Kimmerling, Erica Palma, Ghezzi, Chiara E., and Kaplan, David L.
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HYALURONIC acid , *HYDROGELS , *CROSSLINKED polymers , *SILK fibroin , *TISSUE engineering - Abstract
In this study, silk fibroin and hyaluronic acid (HA) were enzymatically crosslinked to form biocompatible composite hydrogels with tunable mechanical properties similar to that of native tissues. The formation of di-tyrosine crosslinks between silk fibroin proteins via horseradish peroxidase has resulted in a highly elastic hydrogel but exhibits time-dependent stiffening related to silk self-assembly and crystallization. Utilizing the same method of crosslinking, tyramine-substituted HA forms hydrophilic and bioactive hydrogels that tend to have limited mechanics and degrade rapidly. To address the limitations of these singular component scaffolds, HA was covalently crosslinked with silk, forming a composite hydrogel that exhibited both mechanical integrity and hydrophilicity. The composite hydrogels were assessed using unconfined compression and infrared spectroscopy to reveal of the physical properties over time in relation to polymer concentration. In addition, the hydrogels were characterized by enzymatic degradation and for cytotoxicity. Results showed that increasing HA concentration, decreased gelation time, increased degradation rate, and reduced changes that were observed over time in mechanics, water retention, and crystallization. These hydrogel composites provide a biologically relevant system with controllable temporal stiffening and elasticity, thus offering enhanced tunable scaffolds for short or long term applications in tissue engineering. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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19. Curcumin-functionalized silk biomaterials for anti-aging utility.
- Author
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Yang, Lei, Zheng, Zhaozhu, Qian, Cheng, Wu, Jianbing, Liu, Yawen, Guo, Shaozhe, Li, Gang, Liu, Meng, Wang, Xiaoqin, and Kaplan, David L.
- Subjects
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BIOMATERIALS , *AGING prevention , *ANTIOXIDANTS , *FREE radical scavengers , *AQUEOUS solutions , *BIOMEDICAL materials - Abstract
Curcumin is a natural antioxidant that is isolated from turmeric ( Curcuma longa ) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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20. Novel fabrication of fluorescent silk utilized in biotechnological and medical applications.
- Author
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Kim, Dong Wook, Lee, Ok Joo, Kim, Seong-Wan, Ki, Chang Seok, Chao, Janet Ren, Yoo, Hyojong, Yoon, Sung-il, Lee, Jeong Eun, Park, Ye Ri, Kweon, HaeYong, Lee, Kwang Gill, Kaplan, David L., and Park, Chan Hum
- Subjects
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MICROFABRICATION , *FLUORESCENCE , *BIOTECHNOLOGY , *SILK fibroin , *TEXTILE industry , *MANUFACTURING processes - Abstract
Silk fibroin (SF) is a natural polymer widely used and studied for diverse applications in the biomedical field. Recently, genetically modified silks, particularly fluorescent SF fibers, were reported to have been produced from transgenic silkworms. However, they are currently limited to textile manufacturing. To expand the use of transgenic silkworms for biomedical applications, a solution form of fluorescent SF needed to be developed. Here, we describe a novel method of preparing a fluorescent SF solution and demonstrate long-term fluorescent function up to one year after subcutaneous insertion. We also show that fluorescent SF labeled p53 antibodies clearly identify HeLa cells, indicating the applicability of fluorescent SF to cancer detection and bio-imaging. Furthermore, we demonstrate the intraoperative use of fluorescent SF in an animal model to detect a small esophageal perforation (0.5 mm). This study suggests how fluorescent SF biomaterials can be applied in biotechnology and clinical medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
21. Biocompatibility of silk-tropoelastin protein polymers.
- Author
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Liu, Hongjuan, Wise, Steven G., Rnjak-Kovacina, Jelena, Kaplan, David L., Bilek, Marcela M.M., Weiss, Anthony S., Fei, Jian, and Bao, Shisan
- Subjects
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POLYMERS , *SILK fibroin , *TROPOELASTIN , *BIOCOMPATIBILITY , *BIOMATERIALS , *ARTIFICIAL implants , *IMMUNOHISTOCHEMISTRY - Abstract
Abstract: Blended polymers are used extensively in many critical medical conditions as components of permanently implanted devices. Hybrid protein polymers containing recombinant human tropoelastin and silk fibroin have favorable characteristics as implantable scaffolds in terms of mechanical and biological properties. A firefly luciferase transgenic mouse model was used to monitor real-time IL-1β production localized to the site of biomaterial implantation, to observe the acute immune response (up to 5 days) to these materials. Significantly reduced levels of IL-1β were observed in silk/tropoelastin implants compared to control silk only implants at 1, 2 and 3 days post-surgery. Subsequently, mice (n = 9) were euthanized at 10 days (10D) and 3 weeks (3W) post-surgery to assess inflammatory cell infiltration and collagen deposition, using histopathology and immunohistochemistry. Compared to control silk only implants, fewer total inflammatory cells were found in silk/tropoelastin (∼29% at 10D and ∼47% at 3W). Also fewer ingrowth cells (∼42% at 10D and ∼63% at 3W) were observed within the silk/tropoelastin implants compared to silk only. Lower IL-6 (∼52%) and MMP-2 (∼84%) (pro-inflammatory) were also detected for silk/tropoelastin at 10 days. After 3 weeks implantation, reduced neovascularization (vWF ∼43%), fewer proliferating cells (Ki67 ∼58% and PCNA ∼41%), macrophages (F4/80 ∼64%), lower IL-10 (∼47%) and MMP-9 (∼55%) were also observed in silk/tropoelastin materials compared to silk only. Together, these results suggest that incorporation of tropoelastin improves on the established biocompatibility of silk fibroin, uniquely measured here as a reduced foreign body inflammatory response. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
22. Silk fibroin encapsulated powder reservoirs for sustained release of adenosine
- Author
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Pritchard, Eleanor M., Szybala, Cory, Boison, Detlev, and Kaplan, David L.
- Subjects
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CONTROLLED release drugs , *ADENOSINES , *BIOMEDICAL materials , *SILK , *PROTEINASES , *MICROENCAPSULATION , *TREATMENT of epilepsy - Abstract
Abstract: Due to its unique properties, silk fibroin was studied as a biodegradable polymer vehicle for sustained, local delivery of the anticonvulsant adenosine from encapsulated reservoirs. Silk is a biologically derived protein polymer that is biocompatible, mechanically strong and degrades to non-toxic products in vivo. To achieve local, sustained, controlled adenosine release from fully degradable implants, solid adenosine powder reservoirs were coated with silk fibroin. Material properties of the silk coating including thickness, crystallinity and morphology were investigated to assess the relationships between silk coating biomaterial features and adenosine release from silk encapsulated reservoirs. Reservoir coating thickness was varied through manipulation of the silk coating solution concentration and number of coatings applied. Release studies were also performed in proteinase type XIV to model the effects of degradation. Increasing the barrier to diffusion, either by increasing coating thickness or crystallinity was found to delay adenosine burst, decrease average daily release rate, and increase duration of release. In the case of encapsulated reservoirs coated with eight layers of 8% (w/v) silk, a linear release profile was observed and adenosine release was sustained for 14days. The ability to achieve nearly constant release for 2weeks for adenosine via control of the silk coating suggests these encapsulated reservoirs represent a novel system for delivering adenosine. We anticipate that this approach could also be extended to other implant needs and small-molecule drugs to treat a range of clinical needs. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
23. Nanolayer biomaterial coatings of silk fibroin for controlled release
- Author
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Wang, Xianyan, Hu, Xiao, Daley, Andrea, Rabotyagova, Olena, Cebe, Peggy, and Kaplan, David L.
- Subjects
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COATING processes , *SURFACES (Technology) , *SURFACE coatings , *FINISHES & finishing - Abstract
Abstract: An all-aqueous, stepwise deposition process with silk fibroin protein for the assembly of nanoscale layered controlled release coatings was exploited. Model compounds, Rhodamine B, Even Blue and Azoalbumin, representing small molecule drugs and therapeutically relevant proteins were incorporated in the nanocoating process and their loading and release behavior was quantified. In addition, the structure and morphology of the coatings were characterized. Release studies in vitro showed that control of β-sheet crystal content and the multilayer structure of the silk coatings correlated with the release properties of the incorporated compounds. In particular, higher crystallinity and a thicker silk capping layer suppressed the initial burst of release and prolonged the duration of release. These novel coatings and deposition approach provide a unique option to regulate structure and morphology, and thus release kinetics. The results also suggest these systems as a promising framework for surface engineering of biomaterials and medical devices to regulate the release of drugs, when considered with the all-aqueous process involved, the conformal nature of the coatings, the robust material properties of silk fibroin, and the degradability and biocompatibility of this family of protein. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
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