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The innate cartilage extracellular matrix is avascular and plays a vital role in innate chondrocytes. Recapping the crucial components of the extracellular matrix in engineered organs via polymeric gels and bioinspired approaches is promising for improving the regenerative aptitude of encapsulated cartilage/chondrocytes. Conventional gel formation techniques for polymeric materials rely on employing oxidative crosslinking, which is constrained in this avascular environment. Further, poor mechanical properties limit the practical applications of polymeric gels and reduce their therapeutic efficacy. Herein, the purpose of this study was to develop a bioadhesive gel possessing dual crosslinking for engineering cartilage. Tyramine (TYR) was first chemically conjugated to the alginate (ALG) backbone to form an ALG-TYR precursor, followed by the addition of calcium peroxide (CaO

Noninvasive photothermal therapy (PTT) represents a promising direction for more modern and precise medical applications. However, PTT efficacy is still not satisfactory due to the existence of heat shock proteins (HSPs) and poorly targeted delivery. Herein, the design of a nanosystem with improved delivery efficacy for anticancer treatment employing the synergetic effects of reactive oxygen species (ROS)-driven chemodynamic therapy (CDT) to inactivated HSPs with photothermal-hyperthermia was therefore achieved through the development of pH-targeting glycol chitosan/iron oxide enclosed core polypyrrole nanoclusters (GCPI NCs). The designed NCs effectively accumulated toward cancer cells due to their acidic microenvironment, initiating ROS generation via Fenton reaction at the outset and performing site-specific near infrared (NIR)-photothermal effect. A comprehensive analysis of both surface and bulk material properties of the CDT/PTT NCs as well as biointerface properties were ascertained via numerous surface specific analytical techniques by bringing together heightened accumulation of CDT/PTT NCs, which can significantly eradicate cancer cells thus minimizing the side effects of conventional chemotherapies. All of these attributes act in synergy over the cancer cells succeeding in fashioning NC's able to act as competent agents in the MRI-monitored enhanced CDT/PTT synergistic therapy. Findings in this study evoke attention in future oncological therapeutic strategies.

Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency. Statement of significance Herein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.

Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT.

In the fields of biomedicine and tissue engineering, natural polymer-based tissue-engineered scaffolds are used in multiple applications. As a plant-derived polymer, soy protein, containing multiple amino acids, is structurally similar to components of the extra-cellular matrix (ECM) of tissues. It is biological safety provided a good potential to be material for pure natural scaffolds. Moreover, as a protein, the properties of soy protein can be easily adjusted by modifying the functional groups on it. In addition, by blending soy protein with other synthetic and natural polymers, the mechanical characteristics and bioactive behavior of scaffolds can be facilitated for a variety of bio-applications. In this research, soy protein and polysaccharides tapioca starch are used, and gellan gum to develop a protein-based composite scaffold for cell engineering. The morphology and surface chemical composition are characterized via micro-computed tomography (micro-CT), scanning electron microscope (SEM), and fourier-transform infrared (FTIR) spectroscopy. The soy/tapioca/gellan gum (STG) composite scaffolds selectively help the adhesion and proliferation of L929 fibroblast cells while improving the migration of L929 fibroblast cells in STG composite scaffolds as the increase of soy protein proportion of the scaffold. In addition, STG composite scaffolds show great potential in the wound healing model to enhance rapid epithelialization and tissue granulation.

The touchstone for bone replacing or anchoring trauma implants, besides resorption, includes functional ankylosis at a fixation point and replacement by viable functional neo-bone tissues. These parameters redefined the concept of "resorbability" as "bioresorbability." Interference screws are the most commonly used resorbable anchoring implants for anterior cruciate ligament (ACL) reconstruction (surgery). Over the years, the bioresorbable screw fixation armamentarium has amplified countless choices, but instability and postimplantation complications have raised concerns about its reliability and efficacy. Owing to this interest, in this work, bioactive glass fiber-reinforced plastic (BGFP) composites with (BGFPnb5) and without (BGFP5) niobicoxide composing multiplexed network modifiers are reported as bioresorbable bone-anchoring substitutes. These synergistically designed composites have a fabricated structure of continuous, unidirectional BG fibers reinforced in an epoxy resin matrix using "melt-drawing and microfabrication" technology. The BGFP microarchitecture is comprised of multiplexed oxide components that influence bioactive response in a distinctive lophelia atoll-like apatite formation. Furthermore, it assists in the proliferation, adherence, and migration of bone marrow-derived mesenchymal stem cells. It also exhibits superior physicochemical characteristics such as surface roughness, hydrophilic exposure, distinctive flexural strength, and bioresorption. Thus, it induces restorative bone osseointegration and osteoconduction and actuates periosteum function. In addition, the BGFP influences the reduction of DH5-α Escherichia coli in suspension culture, demonstrating potential antibacterial efficacy. In conclusion, the BGFP composite therapeutic efficacy demonstrates distinctive material characteristics aiding in bone regeneration and restoration that could serve as a pioneer in orthopedic regenerative medicine.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

Nanomaterial mediated cancer/tumor photo driven hyperthermia has obtained great awareness. Nevertheless, it is a challenge for improving the hyperthermic efficacy lacking resistance to stimulated thermal stress. We thus developed a bioinspired nano-platform utilizing inclusion complexation between photosensitive polypyrrole (Ppy) nanoparticles (NP) and fucoidan (FU). This FU-Ppy NP proved to be an excellent P-selectin-mediated, lung cancer-cell/tumor targeting delivery and specific accumulation, could augment cancer/tumor oxidative stress levels through producing cellular reactive oxygen species. Potent ROS/photothermal combinational therapeutic effects were exhibited by the bioinspired FU-Ppy NP through a selective P-selectin cancer/tumor targeting aptitude for the lung cancer cells/tumor compared with other nano-formulations. The usage of FU-Ppy NP also involves the potential mechanism of suppressing the biological expression of tumor vascular endothelial growth factor (VEGF). This FU biological macromolecule-amplified photothermally therapeutic nano-platform has promising potential for future medical translation in eradicating numerous tumors.

Patients with irregular, huge burn wounds require time-consuming healing. The skin has an epithelial barrier mechanism. Hence, the penetration and retention of therapeutics across the skin to deep lesion is generally quite difficult and these usually constrain the delivery/therapeutic efficacies for wound healing. Effective burn wound healing also necessitates proper circulation. Conventional polymeric dressing usually exhibits weak mechanical behaviors, obstructing their load-bearing applications. Cold atmospheric plasma (CAP) was used as an efficient, environmentally friendly, and biocompatible process to crosslink methylcellulose (MC) designed for topical administration such as therapeutic substances of platelets (SP) and polyethyleneimine-polypyrrole nanoparticle (PEI-PPy NP)-laden MC hydrogel carriers, and wound dressings. The roles of framework parameters for CAP-treated SP-PEI-PPy NP-MC polymeric complex system; chemical, physical, and photothermal effects; morphological, spectroscopical, mechanical, rheological, and surface properties; in vitro drug release; and hydrophobicity are discussed. Furthermore, CAP-treated SP-PEI-PPy NP-MC polymeric complex possessed augmented mechanical properties, biocompatibility, sustainable drug release, drug-retention effects, and near-infrared (NIR)-induced hyperthermia effects that drove heat-shock protein (HSP) expression with drug permeation to deep lesions. This work sheds light on the CAP crosslinking polymeric technology and the efficacy of combining sustained drug release with photothermal therapy in burn wound bioengineering carrier designs.

The nonspecific distribution and non-targeted heating of chemotherapeutic agents in the human body commonly produce adverse side effects during brain cancer management. Even though an external magnetic field can partially gather extracellular magnetic drug carriers near brain tumor, magnetic guidance alone still cannot precisely identify and target either tumors or healthy tissues due to a lack of selectivity. In this study, we successfully developed thermal and magnetic dual-responsive thermosensitive magnetic liposomes (TML), which co-encapsulates Camptosar (CPT-11) and citric acid-coated magnetic Fe3O4 nanoparticles within the aqueous core and surface-conjugated with Cetuximab (CET) for recognizing over-expressed epidermal growth factor receptors on cancer cell surface. This drug carrier system can control the release of encapsulated drug when exposed to a high-frequency alternating magnetic field (AMF) that elevates the temperature of the liposomal membrane and triggers drug release from TML after their selective endocytosis by cancer cells. By detailed characterizing the physico-chemical and biological properties of liposomes, we demonstrated the liposomal formulation is with high biocompatibility and showed no hemolysis in vitro. Enhanced intracellular uptake of TML-CPT-11-CET by human primary glioblastoma cells (U87) also supported targeted delivery through CET-mediated endocytosis. The treatment of TML-CPT-11-CET solutions by AMF in vitro showed rise in solution temperature and enhanced drug release, which enhanced cytotoxicity of CPT-11 toward U87 though cell apoptosis as revealed from flow cytometry analysis of apoptotic cells and Western blot studies of marker proteins. Finally, the in vivo therapeutic efficacy was demonstrated in mice orthotopic xenograft brain tumor model from IVIS and PET/MRI studies.

Near-infrared–photothermal therapy (NIR-PTT) is a potential modality for cancer treatment. Directing photothermal effects specifically to cancer cells may enhance the therapeutic index for the best treatment outcome. While epithelial growth factor receptor (EGFR) is commonly overexpressed/genetically altered in human malignancy, it remains unknown whether targeting EGFR with tyrosine kinase inhibitor (TKI)-conjugated nanoparticles may direct NIR-PTT to cancers with cellular precision. In the present study, we tested this possibility through the fabrication of a polypyrrole–iron oxide–afatinib nanocomposite (PIA-NC). In the PIA-NC, a biocompatible and photothermally conductive polymer (polypyrrole) was conjugated to a TKI (afatinib) that binds to overexpressed wild-type EGFR without overt cytotoxicity. A Fenton catalyst (iron oxide) was further encapsulated in the NC to drive the intracellular ROS surge upon heat activation. Diverse physical and chemical characterization experiments were conducted. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and -negative cell lines were investigated in the presence and absence of NIR. We found that the PIA-NCs were stable with a size of 243 nm and a zeta potential of +35 mV. These PIA-NCs were readily internalized close to the cell membrane by all types of cells used in the study. The Fourier transform infrared spectra showed 3295 cm−1 peaks; substantial O–H stretching was seen, with significant C=C stretching at 1637 cm−1; and a modest appearance of C–O–H bending at 1444 cm−1 confirmed the chemical conjugation of afatinib but not iron oxide to the NC. At a NIR-PTT energy level that has a minimal cytotoxic effect, PIA-NC significantly sensitizes EGFR-overexpressing A549 lung cancer cells to NIR-PTT-induced cytotoxicity at a rate of 70%, but in EGFR-negative 3T3 fibroblasts the rate was 30%. Within 1 min of NIR-PTT, a surge of intracellular ROS was found in PIA-NC-treated A549 cells. This was followed by early induction of cellular apoptosis for 54 ± 0.081% of A549 cells. The number of viable cells was less than a quarter of a percent. Viability levels of A549 cells that had been treated with NIR or PIA were only 50 ± 0.216% and 80 ± 0.216%, respectively. Only 10 ± 0.816% of NIH3T3 cells had undergone necrosis, meaning that 90 ± 0.124% were alive. Viability levels were 65 ± 0.081% and 81 ± 0.2%, respectively, when only NIR and PIA were used. PIA binding was effective against A549 cells but not against NIH3T3 cells. The outcome revealed that higher levels of NC + NIR exposure caused cancer cells to produce more ROS. In summary, our findings proved that a molecularly targeted NC provides an orchestrated platform for cancer cell-specific delivery of NIR-PTT. The geometric proximity design indicates a novel approach to minimizing the off-target biological effects of NIR-PTT. The potential of PIA-NC to be further developed into real-world application warrants further investigation.

Cold atmospheric plasma (CAP) is a promising tool to overcome certain cancerous and precancerous conditions in dermatology. A scheme of transferred CAP was first developed to treat melanoma (B16F10) skin cancer cells as well as non-malignant (L929) cells in vitro. CAP was transferred using a silicone tube with a jet system that was developed and was assessed as to whether it could generate reactive oxygen and nitrogen species (RONS) at near-room temperature. The transferred CAP was characterized electrically and spectroscopically. Biological data showed that the transferred CAP killed cancer cells but not non-malignant (L929) cells. Plasma treatment was effective with a time duration of 30 s, whereas non-malignant (L929) cells were less damaged during plasma treatment. In addition, catalase (CAT) enzyme was applied to neutralize and detoxify the RONS generated by the transferred CAP. These findings suggest that transferred CAP can be considered a melanoma cancer therapy.

Chih-Wei Chiang,1,2,* Chih-Hwa Chen,3– 6,* Yankuba B Manga,4 Shao-Chan Huang,4 Kun-Mao Chao,1,7 Pei-Ru Jheng,4 Pei-Chun Wong,4 Batzaya Nyambat,4 Mantosh Kumar Satapathy,4 Er-Yuan Chuang4,8 1Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 10617, Taiwan; 2Department of Orthopedics, Taipei Medical University Hospital, Taipei, 11031, Taiwan; 3Department of Orthopedics, Taipei Medical University–Shuang Ho Hospital, New Taipei City, 23561, Taiwan; 4Graduate Institute of Biomedical Materials and Tissue Engineering, International PhD Program in Biomedical Engineering, School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan; 5School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan; 6Research Center of Biomedical Device, Taipei Medical University, Taipei, 11031, Taiwan; 7Department of Computer Science and Information Engineering, National Taiwan University, Taipei, 10617, Taiwan; 8Cell Physiology and Molecular Image Research Center, Taipei Medical University–Wan Fang Hospital, Taipei, 116, Taiwan*These authors contributed equally to this workCorrespondence: Er-Yuan Chuang Email eychuang@tmu.edu.twBackground and Purpose: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration.Methods: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy.Results: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups.Conclusion: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.Keywords: strontium ranelate, drug formulation, nanoparticles, hyaluronic acid, glycol chitosan

Several studies have applied tricalcium phosphate (TCP) or autografts in bone tissue engineering to enhance the clinical regeneration of bone. Unfortunately, there are several drawbacks related to the use of autografts, including a risk of infection, blood loss, limited quantities, and donor-site morbidities. Platelet-rich fibrin (PRF) is a natural extracellular matrix (ECM) biomaterial that possesses bioactive factors, which can generally be used in regenerative medicine. The goal of the present investigation was to develop osteoconductive TCP incorporated with bioactive PRF for bio-synergistic bone regeneration and examine the potential biological mechanisms and applications. Our in vitro results showed that PRF plus TCP had excellent biosafety and was favorable for initiating osteoblast cell attachment, slow release of bioactive factors, cell proliferation, cell migration, and ECM formation that potentially impacted bone repair. In a rabbit femoral segmental bone defect model, regeneration of bone was considerably augmented in defects locally implanted by PRF plus TCP according to radiographic and histologic examinations. Notably, the outcomes of this investigation suggest that the combination of PRF and TCP possesses novel synergistic and bio-inspired functions that facilitate bone regeneration.

A novel device for cholesteric liquid crystal (CLC)-based microfluidic chips, accommodated in a polydimethylsiloxane material, was invented. In this device, the reorientation of the CLCs was consistently influenced by the surface of the four channel walls and adjacent CLCs. When the inside of the microchannel was coated with the alignment layer, the CLCs oriented homeotropically in a focal conic state under cross-polarizers. Once antigens had bound onto antibodies immobilized onto the orientation sheet-coated channel walls, the light intensity of the CLC molecules converted from a focal conic state to a bright planar state caused by disrupting the CLCs. By means of utilizing pressure-propelling flow, the attachment of antigen/antibody to the CLCs should be detectable within consecutive sequences. The multi-microfluidic CLC-based chips were verified by measuring bovine serum albumin (BSA) and immune complexes of pairs of BSA antigen/antibody. We showed that the multiple microfluidic immunoassaying can be used for measuring BSA and pairs of antigen/antibody BSA with a detection limit of about 1 ng/mL. The linear range is 0.1 μg/mL–1 mg/mL. A limit of immune detection of pairs of BSA antigens/antibodies was 10 ng/mL of BSA plus 1000 ng/mL of the anti-BSA antibodies was observed. According to this innovative creation of immunoassaying, an unsophisticated multi-detection device with CLC-based labeling-free microfluidic chips is presented.

Spurred by recent progress in biomaterials and therapeutics, stimulus-responsive strategies that deliver an active substance in temporal-, spatial-, and dose-controlled fashions have become achievable. Implementation of such strategies necessitates the use of bio-safe materials that are sensitive to a specific pathological incitement or that, in response to a precise stimulus, undergo hydrolytic cleavage or a change in biomolecular conformation. An innovative design of polymeric stimulus-responsive systems should controllably release a drug or degrade the drug carrier in response to specific lesion enzymes. Wound healing is a great challenge due to various hidden factors such as pathogenic infections, neurovascular diseases, excessive exudates, lack of an effective therapeutic delivery system, low cell proliferation, and cell migration. In addition, long-term use of antibiotics in chronic wound management can result in side effects and antimicrobial resistance. Novel treatments with antibacterial pharmaceuticals thus vitally need to be developed. Recently, graphene and graphene family members have emerged as shining stars among biomaterials for wound-healing applications due to their excellent bioactive properties, which can overcome limitations of current wound dressings and fulfill wound-healing requirements. Herein, we developed a feasible approach to impregnate graphene oxide (GO) into genipin-crosslinked gelatin (3GO) hydrogels to enzymatically control GO release. The developed hydrogels were characterized by chemical, physical, morphological, and cellular analyses. The results proved that the 3GO1 hydrogel is biocompatible and significantly enhanced the mechanical strength by encapsulating GO. Moreover, the rate of GO release depended on the crosslinking degree and environmental enzyme levels. Enzymatically released GO displayed uniform dispersity, retained its antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa through sharp edges and wrapping mechanisms, and promoted human fibroblast migration. This multifunctional hydrogel we developed with antibacterial efficacy is suitable for future application as wound dressings.

Er-Yuan Chuang,1 Ping-Yuan Lin,1 Po-Feng Wang,1 Tsung-Rong Kuo,1 Chih-Hwa Chen,1– 4 Yankuba B Manga,1 Yu-Cheng Hsiao1,5 1Graduate Institute of Biomedical Optomechatronics; Graduate Institute of Nanomedicine and Medical Engineering; International PhD Program in Biomedical Engineering; Graduate Institute of Biomedical Materials and Tissue Engineering; School of Biomedical Engineering; College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 2Department of Orthopedics, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; 3School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Research Center of Biomedical Device, Taipei Medical University, Taipei, Taiwan; 5Cell Physiology and Molecular Image Research Center, Taipei Medical University–Wan Fang Hospital, Taipei, TaiwanCorrespondence: Yu-Cheng HsiaoGraduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, TaiwanTel +886-2-27361661Email ychsioa@tmu.edu.twIntroduction: The sensitive interfacial interaction of liquid crystals (LC) holds potential for precision biosensors. In the past, the developments of LC biosensors were limited by the complicated manufacturing process, which hinders commercialization and wider applications of such devices. In this report, we demonstrate the first nano-structural polymeric stabilized-cholesteric LC (PSCLC) thin films to be a new label-free biosensing technology.Methods: The transmission spectra of PSCLC devices were measured by the fiber-optic spectrometer with high-resolution. In addition, a smartphone was set on the stage, and the camera of smartphone was placed and aligned with a set of lenses embedded in the designed stage. To decrease the chromatic and spherical aberrations, an achromatic lens set composition, consisting of both dual-convex lens and concave-plane lens, was applied for measuring and imaging the PSCLC texture. The average and the estimated standard deviation (SD) were used to present quantitative experimental results. The test BSA was immobilized and fulfilled by the ceramic silicon-constructed DMOAP-coated glass in aqueous BSA solutions at 1 mg/mL, 1 μg/mL, and 1 ng/mL.Results: The fabrication process of PSCLC is much simplified compared to previous LC biosensors. The color of PSCLC biosensor altered with the BSA concentration, making detection result easy to read. The detection limit of 1 ng/mL is achieved for label-free PSCLC biosensor. The PSCLC biosensor was able to successfully detect due to the albumin concentration’s alteration, with a linear range of 1 ng/mL– 2 mg/mL. Thus, the label-free-proposed design-integrated nanoscale PSCLCs smartphone-based biosensor could successfully detect BSA in a preclinical urine sample.Conclusion: Finally, we propose a design to integrate the PSCLC biosensor with a smartphone. The PSCLC owns potential for high performance, low cost for detecting various disease biomarkers in home use. Owing to its great potential for high performance and low cost, the PSCLC biosensors can be used as a label-free point-of-care for detecting various disease biomarkers for patients in care homes.Keywords: polymer-stabilized cholesteric liquid crystal, ceramic silicon compound, trimethoxysilyl, constructed DMOAP, label-free, biosensor, point-of-care, bovine serum albumin

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo. This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.

Curcumin can reduce the production of brain inflammatory mediators and symptoms of brain diseases. However, a large amount of free curcumin needs to be administered to achieve an effective level in the brain because of its poor water-solubility. Fucoidan and chitosan were reported to respectively target P-selectin and acidic microenvironment expressed by pathologically inflammatory cells/tissues. Herein, the self-assembly of chitosan and fucoidan which could encapsulate curcumin was developed to form the multi-stimuli-responsive nanocarriers, and their pathological pH- and P-selectin-responsive aspects were characterized. Through intranasal delivery to the brain, these curcumin-containing chitosan/fucoidan nanocarriers with dual pH-/P-selectin-targeting properties to the brain lesions improved drug delivery, distribution, and accumulation in the inflammatory brain lesions as evidenced by an augmented inhibitory effect against brain inflammation. This promising multifunctional nanocarrier with a novel drug-delivery route should allow potential clinical biomedical uses by neurosurgeon in the future.

Understanding the molecular mechanisms of graphene oxide (GO)-based biomaterials is important for logical biomedical applications. Previous studies have revealed biointeractions between GO and immune effector cells, but the effects on neutrophils, crucial cells in the immune system, have not been thoroughly discussed. In this study, GO nanoformulations were synthesized with different functional groups, including GO, GO-carboxylated (GO-COOH), and PEGylated GO (GO-PEG), with different surface features, which were elucidated using imaging methods and surface-sensitive quantitative spectroscopic techniques, including atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoemission spectroscopy (XPS). The GO-based nanoformulations elicited reactive oxygen species (ROS) generation and neutrophil extracellular trap (NET) formation in human neutrophils. Nanoformulated GO stimulates NET development via the formation of ROS. An endocytosis study revealed that nanoformulated GO facilitated internalization by neutrophils via macropinocytosis and actin-dependent phagocytosis. Importantly, calcium mobilization and phosphorylation proteins such as mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38) and AKT were involved in the activation of neutrophils. These findings offer the first verification that nanoformulated GO exhibits direct effects on human neutrophils.

The cell-derived extracellular matrix (ECM) is associated with a lower risk of pathogen transfer, and it possesses an ideal niche with growth factors and complex fibrillar proteins for cell attachment and growth. However, the cell-derived ECM is found to have poor biomechanical properties, and processing of cell-derived ECM into gels is scarcely studied. The gel provides platforms for three-dimensional cell culture, as well as injectable biomaterials, which could be delivered via a minimally invasive procedure. Thus, in this study, an adipose-derived stem cell (ADSC)-derived ECM gel was developed and cross-linked by genipin to address the aforementioned issue. The genipin cross-linked ADSC ECM gel was fabricated via several steps, including rabbit ADSC culture, cell sheets, decellularization, freeze&ndash, thawing, enzymatic digestion, neutralization of pH, and cross-linking. The physicochemical characteristics and cytocompatibility of the gel were evaluated. The results demonstrated that the genipin cross-linking could significantly enhance the mechanical properties of the ADSC ECM gel. Furthermore, the ADSC ECM was found to contain collagen, fibronectin, biglycan, and transforming growth factor (TGF)-&beta, 1, which could substantially maintain ADSC, skin, and ligament fibroblast cell proliferation. This cell-derived natural material could be suitable for future regenerative medicine and tissue engineering application.

Combined applications of composite materials are very important in today’s science, especially those of liquid crystal (LC) materials. Visualization of near-infrared (NIR) with zero power consumption using a combination of photothermal and LC materials is urgently needed. In this study, a device was constructed from thermosensitive cholesteric LC (CLC) and nano-level polypyrrole materials, and named a photothermal polypyrrole nano-pigment-integrated with CLC (PNCLC) display element. A change in the reflected light of the CLC display element was achieved by the photoabsorption-exothermic characteristics of polypyrrole, which absorbs NIR light to drive the photothermal performance. The temperature and color change caused by the absorption of NIR light resulted in the CLC display element automatically indicating a change in the NIR intensity. In addition, to increase the range of potential applications, conductive soft polyethylene terephthalate (PET) substrates were used as display elements. To the best of our knowledge, this is the first study to illustrate a visual display element of NIR light intensity with zero power consumption and explore its potential theranostic applications.

Autologous skin grafts, which can cause donor site morbidity, are currently used to treat deep wounds. To improve the regeneration of poorly healing wounds, cell-derived extracellular matrix (ECM) scaffolds are garnering great research interest due to their associated lower risks of pathogen transfer and immune rejection. However, the mechanical properties of cell-derived ECM scaffolds are inferior when compared to those of tissue-derived ECM scaffolds. To overcome this drawback, different amounts (10, 20, 50, and 100 μg mL−1) of graphene oxide (GO) and genipin (1% w/v) were applied to adipose stem cell (ASC)-derived ECM sponges. There are still only a few studies employing cell-derived extracellular matrices as biomimetic scaffolds for biomedical applications. The aim of our study was to develop biocompatible, biodegradable, low immunogenic, and genipin-crosslinked ASC-derived ECM sponges containing a suitable amount of GO for skin-tissue engineering. Sponges were fabricated using cultures of ASCs, cell sheets, and decellularization of an ASC cell sheet, freeze-thawing, and crosslinking in a sequential manner. Scanning electron microscopic analyses of the sponges demonstrated a highly porous microstructure with a pore size of 71.22 ± 19.52 μm. The in vitro degradation rate was found to be significantly higher in the non-crosslinked ECM sponges and pure ECM sponges than in the genipin-crosslinked ECM sponges. During an in vivo study, we investigated the material feasibilities and degradability of the constructed ECM sponges as a suitable skin tissue-engineering scaffold in a xenogenic animal (rat) model for 4 weeks. After subcutaneous implantation, the ECM sponges containing a medium amount of GO showed appropriate biodegradation with a lower inflammatory reaction. Hence, the fabricated ECM sponges might be a suitable xenogenous skin substitute for full-thickness skin defects and in other future soft-tissue engineering applications, such as healing partial tears of the anterior cruciate ligament.

Macrophages have a pivotal role in chronic inflammatory diseases (CIDs), so imaging and controlling activated macrophage is critical for detecting and reducing chronic inflammation. In this study, photodynamic selenium nanoparticles (SeNPs) with photosensitive and macrophage-targeting bilayers were developed. The first layer of the photosensitive macromolecule was composed of a conjugate of a photosensitizer (rose bengal, RB) and a thiolated chitosan (chitosan-glutathione), resulting in a plasmonic coupling-induced red shift and broadening of RB absorption bands with increased absorption intensity. Electron paramagnetic resonance (EPR) and diphenylanthracene (DPA) quenching studies revealed that the SeNPs that were coated with the photosensitive layer were more effective than RB alone in producing singlet oxygen (1O2) under photoirradiation. The second layer of the activated macrophage-targetable macromolecule was synthesized by conjugation of hyaluronic acid with folic acid using an ethylenediamine linke...

Herein, we report the cartilage tissue engineering application of nanographene oxide (NGO)-reinforced gelatin hydrogel fabricated by utilizing a microplasma-assisted cross-linking method. NGO sheets with surface functionalities were introduced to enhance the mechanical and biomedical properties of gelatin-based hydrogels. Highly energetic reactive radicals were generated from the nonthermal plasma (NTP), which is used to facilitate the cross-linking and polymerization during the polymeric hydrogel fabrication. The NTP treatment substantially reinforced a small amount (1 wt %) of NGO into the gelatin hydrogel. Systematic material characterization thus shows that the fabricated hydrogel possessed unique properties such as moderate surface roughness and adhesiveness, suitable pores sizes, temperature-dependent viscoelasticity, and controllable degradability. In vitro studies demonstrated that the as-fabricated hydrogel exhibited excellent cell-material interactions with SW 1353 cells, bone marrow-derived mesenchymal stem cells, and a rat chondrocyte cell line, thereby exhibiting appropriate cytocompatibility for cartilage tissue engineering applications. Furthermore, an in vivo study indicated that the formation of a healthy hyaline cartilage after the microfracture was enhanced by the fabricated hydrogel implant, offering a potential biocompatible platform for microfracture-based cartilage reconstructive surgery.

Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment.

Heterogeneous Fenton reactions have been proven to be an effective and promising selective cancer cell treatment method. The key working mechanism for this method to achieve the critical therapeutic selectivity however remains unclear. In this study, we proposed and demonstrated for the first time the critical role played by catalase in realizing the therapeutic selectivity for the heterogeneous Fenton reaction-driven cancer cell treatment. The heterogeneous Fenton reaction, with the lattice ferric ions of the solid catalyst capable of converting H2O2 to highly reactive hydroxyl radicals, can effectively eradicate cancer cells. In this study, SnFe2O4 nanocrystals, a recently discovered outstanding heterogeneous Fenton catalyst, were applied for selective killing of lung cancer cells. The SnFe2O4 nanocrystals, internalized into the cancer cells, can effectively convert endogenous H2O2 into highly reactive hydroxyl radicals to invoke an intensive cytotoxic effect on the cancer cells. On the other hand, cata...

Engineered skin that can facilitate tissue repair has been a great advance in the field of wound healing. A well-designed dressing material together with active biological cues such as cells or growth factors can overcome the limitation of using auto-grafts from patients. Recently, many studies showed that human adipose-derived stem cells (hASCs) can be used to promote wound healing and skin tissue engineering. hASCs have already been widely applied for clinical trials. hASCs can be harvested abundantly because they can be easily isolated from fat tissue known as the stromal vascular fraction (SVF). On the other hand, increasing studies have proven that cells from spheroids can better simulate the biological microenvironment and can enhance the expression of stemness markers. However, a three-dimensional (3D) scaffold that can harbor implanted cells and can serve as a skin-repaired substitute still suffers from deficiency. In this study, we applied a gelatin/microbial transglutaminase (mTG) hydrogel to encapsulate hASC spheroids to evaluate the performance of 3D cells on skin wound healing. The results showed that the hydrogel is not toxic to the wound and that cell spheroids have significantly improved wound healing compared to cell suspension encapsulated in the hydrogel. Additionally, a hydrogel with cell spheroids was much more effective than other groups in angiogenesis since the cell spheroid has the possibility of cell&ndash, cell signaling to promote vascular generation.