Zirconium ion mediated collagen nanofibrous hydrogels with high mechanical strength.

Low mechanical strength is still the key question for collagen hydrogel consisting of nanofibrils as hard tissue repair scaffolds with no loss of biological function. In this work, novel collagen nanofibrous hydrogels with high mechanical strength were fabricated based on the pre-protection of trisodium citrate masked Zr(SO4)2 solution for collagen self-assembling nanofibrils and then further coordination with Zr(SO4)2 solution. The mature collagen nanofibrils with d-period were observed in Zr(IV) mediated collagen hydrogels by AFM when the Zr(IV) concentration was ≥ 10 mmol/L, and the distribution of zirconium element was uniform. Due to the coordination of Zr(IV) with ─COOH, ─NH2 and ─OH within collagen and the tighter entanglement of collagen nanofibrils, the elastic modulus and compressive strength of Zr(IV) mediated collagen nanofibrous hydrogel were 208.3 and 1103.0 kPa, which were approximate 77 and 12 times larger than those of pure collagen hydrogel, respectively. Moreover, the environmental stability such as thermostability, swelling ability and biodegradability got outstanding improvements and could be regulated by Zr(IV) concentration. Most importantly, the resultant hydrogel showed excellent biocompatibility and even accelerated cell proliferation.

Converting Acellular Dermal Matrix into On-Demand Versatile Skin Scaffolds by a Balanceable Crosslinking Approach for Integrated Infected Wounds Therapy.

Ideal tissue-engineered skin scaffolds should possess integrated therapeutic effects and multifunctionality, such as broad-spectrum antibacterial properties, adjustable mechanical properties, and bionic structure. Acellular dermal matrix (ADM) has been broadly used in many surgical applications as an alternative treatment to the "gold standard" tissue transplantation. However, insufficient broad-spectrum antibacterial and mechanical properties for therapeutic efficacy limit the practical clinical applications of ADM. Herein, a balanceable crosslinking approach based on oxidized 2-hydroxypropyltrimethyl ammonium chloride chitosan (OHTCC) was developed for converting ADM into on-demand versatile skin scaffolds for integrated infected wounds therapy. Comprehensive experiments show that different oxidation degrees of OHTCC have significative influences on the specific origins of OHTCC-crosslinked ADM scaffolds (OHTCC-ADM). OHTCC with an oxidation degree of about 13% could prosperously balance the physiochemical properties, antibacterial functionality, and cytocompatibility of the OHTCC-ADM scaffolds. Owing to the natural features and comprehensive crosslinking effects, the proposed OHTCC-ADM scaffolds possessed the desirable multifunctional properties, including adjustable mechanical, degradable characteristics, and thermal stability. In vitro/in vivo biostudies indicated that OHTCC-ADM scaffolds own well-pleasing broad-spectrum antibacterial performances and play effectively therapeutic roles in treating infection, inhibiting inflammation, promoting angiogenesis, and promoting collagen deposition to enhance the infected wound healing. This study proposes a facile balanceable crosslinking approach for the design of ADM-based versatile skin scaffolds for integrated infected wounds therapy.

Two-Layered Biomimetic Flexible Self-Powered Electrical Stimulator for Promoting Wound Healing.

The repair of wound damage has been a common problem in clinic for a long time. Inspired by the electroactive nature of tissues and the electrical stimulation of wounds in clinical practice, the next generation of wound therapy with self-powered electrical stimulator is expected to achieve the desired therapeutic effect. In this work, a two-layered self-powered electrical-stimulator-based wound dressing (SEWD) was designed through the on-demand integration of the bionic tree-like piezoelectric nanofiber and the adhesive hydrogel with biomimetic electrical activity. SEWD has good mechanical properties, adhesion properties, self-powered properties, high sensitivity, and biocompatibility. The interface between the two layers was well integrated and relatively independent. Herein, the piezoelectric nanofibers were prepared by P(VDF-TrFE) electrospinning, and the morphology of the nanofibers was controlled by adjusting the electrical conductivity of the electrospinning solution. Benefiting from its bionic dendritic structure, the prepared piezoelectric nanofibers had better mechanical properties and piezoelectric sensitivity than native P(VDF-TrFE) nanofibers, which can convert tiny forces into electrical signals as a power source for tissue repair. At the same time, the designed conductive adhesive hydrogel was inspired by the adhesive properties of natural mussels and the redox electron pairs formed by catechol and metal ions. It has bionic electrical activity matching with the tissue and can conduct the electrical signal generated by the piezoelectric effect to the wound site so as to facilitate the electrical stimulation treatment of tissue repair. In addition, in vitro and in vivo experiments demonstrated that SEWD converts mechanical energy into electricity to stimulate cell proliferation and wound healing. The proposed healing strategy for the effective treatment of skin injury was provided by developing self-powered wound dressing, which is of great significance to the rapid, safe, and effective promotion of wound healing.

In Situ Cross-Linked Collagen-Based Biological Patch Integrating Anti-Infection and Anti-Calcification Properties.

Acellular dermal matrix (ADM) can be used as collagen-based biological patches for regeneration and repair of soft tissues in vivo. However, the problems of calcification and infection during treatment with patches can lead to premature patch failure and even to a severely increased risk of recurrence. In this study, first, porcine ADM (pADM) grafted with vinyl underwent an in situ cross-linking reaction in the presence of an initiator, while quaternary ammonium groups were introduced into the pADM during the cross-linking process to obtain MA-DMC-pADM, which is a biological patch with anti-infection and anti-calcification properties. The results of physicochemical property tests of the material showed that the pADM after cross-linking had better physical and mechanical properties. Importantly, antibacterial and anti-calcification experiments showed that MA-DMC-pADM had a good antibacterial and anti-calcification effect. Therefore, the MA-DMC-pADM biological patch facilitates their longer-lasting effectiveness, allowing pADM to be used in a wider range of applications.

Fabrication of high-strength, flexible, porous collagen-based scaffolds to promote tissue regeneration.

Collagen-based scaffolds lack mechanical strength, flexibility, and tunable pore structure, affecting tissue repair outcomes and restricting their wide clinical application. Here, two kinds of scaffolds were prepared by a combination of vacuum homogenization, natural air drying, water soaking, lyophilization, and crosslinking. Compared with the scaffolds made of collagen molecules (Col-M), the scaffolds made of collagen aggregates (Col-A) exhibited higher mechanical strength (ultimate tensile strength: 1.38 â€‹± â€‹0.26 â€‹MPa vs 15.46 â€‹± â€‹1.55 â€‹MPa), stronger flexibility, advanced cell adhesion, survival, and proliferation. Subcutaneous implantation in rats showed that Col-A scaffolds promoted cell infiltration, macrophage polarization, and vascularization. Furthermore, the Col-A scaffolds inhibited abdominal bulges due to their adequate mechanical support, and they also promoted vascularized muscle regeneration in a rat abdominal hernia defect model. Our study provides a novel strategy for generating high-strength, flexible, porous collagen-based scaffolds, which can be applied to tissue repair with mechanical strength requirements. It broadens their application range in the field of regenerative medicine.

Origin of critical nature and stability enhancement in collagen matrix based biomaterials: Comprehensive modification technologies.

Collagen is the most abundant protein in animals and one of the most important extracellular matrices that chronically plays an important role in biomaterials. However, the major concern about native collagen is the lack of its thermal stability and weak resistance to proteolytic degradation. Currently, a series of modification technologies have been explored for critical nature and stability enhancement in collagen matrix-based biomaterials, and prosperously large-scale progress has been achieved. The establishment of covalent bonds among collagen noumenon has been verified assuringly to have pregnant influences on its physicochemical properties and biological properties, enlightening to discuss the disparate modification technologies on specific effects on the multihierarchical structures and pivotal performances of collagen. In this review, various existing modification methods were classified from a new perspective, scilicet whether to introduce exogenous substances, to reveal the basic scientific theories of collagen modification. Understanding the role of modification technologies in the enhancement of collagen performance is crucial for developing novel collagen-based biomaterials. Moreover, the different modification effects caused by the interaction sites between the modifier and collagen, and the structure-activity relationship between the structure of the modifier and the properties of collagen were reviewed.

Heparinized Collagen Scaffolds Based on Schiff Base Bonds for Wound Dressings Accelerate Wound Healing without Scar.

Skin wound healing is a complex process with multiple growth factors and cytokines participating and regulating each other. It is essential to develop novel wound dressings to accelerate the wound healing process. In this study, we developed the heparinized collagen scaffold materials (OL-pA), and the cross-linking reaction was based on the Schiff base reaction between pig acellular dermal matrix (pADM) and dialdehyde low molecular weight heparin (LMWH). Compared with pADM, the OL-pA modified by cross-linking still retained the triple helix structure of native collagen. When the dosage of the OL cross-linking agent was 12 wt %, the cross-linking density of OL-pA was 49.67%, the shrinkage temperature was 75.6 °C, the tensile strength was 14.62 MPa, the elongation at break was 53.14%, and the water contact angle was 25.1°, all of which were significantly improved compared with pADM. The cytocompatibility test showed that L929 cells adhered better on the surface of OL-pA scaffolds, and the proliferation ability of primary fibroblasts was enhanced. In vivo experiments showed that the OL-pA scaffolds could better accelerate wound healing, more effectively promote the positive expression of bFGF, PDGF, and VEGF growth factors, accelerate capillary angiogenesis, and promote wound scarless healing. In summary, the OL-pA scaffolds have more excellent hygrothermal stability, mechanical properties, hydrophilicity, and cytocompatibility. Especially the scaffolds have significant pro-healing properties for the full-thickness skin wound of rats and are expected to be a potential pro-healing collagen-based wound dressing.

A novel thermosensitive growth-promoting collagen fibers composite hemostatic gel.

As a feasible solution to massive blood loss in emergencies, ensuring the availability of absorbable exogenous topical hemostatic materials is a major current focus. Among the available materials, collagen is a surprising presence, but that does not mean that it is an ideal material from every aspect. Collagen fibers (CFs) and collagen have the same composition in terms of matter, but they have differing spatial structures and hierarchies. CFs can be directly seen as a slight advance on collagen, yet disadvantages relating to their mono-functionality and dosage form restrict their further utilization. It is worth noting that technology for extracting Bletilla striata polysaccharide (BSP), a natural derivative of Bletilla striata, is becoming more advanced. Based on extensive surveys and development studies, hydrogels can show extraordinary development flexibility. In particular, when it comes to wound adaptability and stimuli responsiveness, in situ gels show many advantages. Therefore, we introduced a collagen-based biocompatible and efficient thermosensitive hemostatic hydrogel material (COF). COF is a stable, safe, and bioactive material, and multiple characterization tests confirm this. Upon adjusting the ratios of different materials, COF-3, showing the most comprehensive performance, best in vitro hemostatic effects, good gelation speed, and good cell compatibility, was selected. COF-3 was applied during the in vivo hemostasis testing of a rat hemorrhage model, and COF-3 achieved hemostasis within 30 s. COF shows promising application and clinical potential, providing an effective route to the achievement of in vivo minimally invasive hemostasis and laying a solid foundation for the development of functional hemostatic gels.

Anti-calcification potential of collagen based biological patch crosslinked by epoxidized polysaccharide.

Biological patch is a kind of tissue substitute material derived from natural polymer materials for the repair of human soft tissue defects. The serious calcification of biological patch after implantation is one of the reasons for the decline and failure of patch. In previous studies, we synthesized a new biomaterial crosslinker epoxidized chitosan quaternary ammonium salt (EHTCC) and used it for the crosslinking of porcine acellular dermal matrix (pADM). The prepared EHTCC-pADM had good mechanical properties, biocompatibility and healing promoting properties. In order to broaden its application scenarios, the related properties of EHTCC-pADM as implant patch were further explored in this study. The results of X-ray diffraction (XRD) measurements showed that the structure of pADM did not change much before and after the crosslinking of EHTCC, which was conducive to the maintenance of the excellent biological properties of pADM. According to the enzymatic degradation resistance test in vitro, the resistance of EHTCC-pADM to type I collagenase degradation was significantly improved compared with non -crosslinked pADM. And with the increase of the amount of EHTCC, its degradation resistance was stronger. The experimental results showed that EHTCC-pADM can well support the growth of L929 fibroblasts and has good anti-calcification properties in vitro and in vivo.

Crosslinking of dialdehyde heparin: a new strategy for improving the anticoagulant properties of porcine acellular dermal matrix.

The anticoagulant properties of valve materials are essential to maintain blood patency after artificial valve implantation. Porcine acellular dermal matrix (pADM) has low immunogenicity, good biocompatibility, and can reduce calcification by eliminating heterogeneous cells. However, its main component is collagen, which has strong coagulation function and poor anticoagulant activity. When used in heart valve materials, it can easily coagulate and form a life-threatening thrombus. Therefore, it is necessary to improve its anticoagulant performance. The glutaraldehyde (GA) cross-linked valves widely used clinically are easy to calcify with poor anticoagulant performance and cytotoxicity. In this study, dialdehyde heparin containing cross-linking active aldehyde groups was prepared by sodium periodate oxidation, then it was used for crosslinking with pADM to chemically modify its anticoagulant performance. Compared with GA cross-linked pADM (GA-pA), dialdehyde heparin cross-linked pADM (OL-pA) has better thermal stability and biocompatibility, especially its anticoagulant and antiplatelet adhesion were significantly improved, which can reduce the incidence of coagulation, thrombocytopenia and bleeding. In summary, dialdehyde heparin is expected to be applied to modify the anticoagulant properties of pADM and has great potential for the preparation and clinical application of anticoagulant materials such as heart valves and artificial blood vessels.

Colorimetric detection for uranyl ions in water using vinylphosphonic acid functionalized gold nanoparticles based on smartphone.

A simple and portable colorimetric sensor for colorimetric detection of UO22+ in aqueous solution based on vinylphosphonic acid functionalized gold nanoparticles (VPA-AuNPs) has been developed. The VPA-AuNPs solution was prepared by sodium borohydride reduction in the presence of vinylphosphonic acid. The addition of UO22+ would induce aggregation of VPA-AuNPs, resulting in the color change from wine-red to blue, and red-shift of the ultraviolet-visible (UV-vis) spectra. The UO22+ assay based on VPA-AuNPs showed good selectivity and sensitivity, with a limit of detection to be approximately 2.0 µM by naked eyes and 1.07 µM by UV-vis (S/N = 3) respectively. Additionally, a smartphone with a free application named "PhotoMetrix" was employed to estimate the color intensities (red, green, blue value) of VPA-AuNPs in the presence of UO22+ with different concentrations, and the concentration of UO22+ samples could be conveniently exported by the calculated univariate calibration curves. This method shows good feasibility for on-site UO22+ detection in an aqueous solution.

Polyglutamic acid grafted dopamine modified collagen-polyvinyl alcohol hydrogel for a potential wound dressing.

Natural collagen has good biocompatibility and ability to promote tissue regeneration and repair, but the poor mechanical properties and intolerance of degradation of natural collagen limit its applications in the biomedical field. In this research, we synthesized a skin wound repair hydrogel with good biological activity, high strength and excellent water absorption properties. Inspired by the theory of wet healing, dopamine was introduced into the side chain of the water-absorbing polymer polyglutamic acid to synthesize a cross-linking agent (PGAD) with both water absorption and cell adhesion ablities, and then it was introduced into collagen/polyvinyl alcohol (PVA-COL) system to form a double network hydrogel. Scanning electron microscope observation of the morphological characteristics of the hydrogel showed that after the introduction of PGAD, the hydrogel formed an obvious pore structure, and the swelling rate showed that the introduction of PGAD significantly improved the water absorption rate of the hydrogel.In addition, PVA-COL-PGAD hydrogel has good mechanical properties and water absorption behavior.In vitro experimental results revealed that the hydrogel has good biocompatibility. In vivo wound healing experiments showed that hydrogel can promote wound healing process.These results indicated that our hydrogel has great potential as a medical wound dressing.

Highly stable collagen scaffolds crosslinked with an epoxidized natural polysaccharide for wound healing.

As a biocompatible and bioactive natural tissue engineering collagen scaffold, porcine acellular dermal matrix (pADM) has limitations for the application in tissue regeneration due to its low strength and rapid biodegradation. Herein, to get a good wound dressing, the epoxy group was added to N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) to synthesize the epoxidized N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (EHTCC), and the porcine acellular dermal matrix was modified with EHTCC at different dosage of 0, 4, 8, 12, 16 and 20%. The properties of the EHTCC-pADM were evaluated. The results indicated that the thermal stability and mechanical properties of EHTCC-pADM were remarkably improved, and the natural conformation of the matrix was maintained, which was beneficial to natural and excellent biological properties of the pADM. According to the test results of water contact angle, the hydrophilicity of the material was improved, which is conducive to cell adhesion, proliferation and growth. Cytotoxicity experiments showed that the introduction of EHTCC would not adversely affect the biocompatibility of the materials. In vivo experiments showed that EHTCC-pADM could promote wound healing. In conclusion, EHTCC-pADM is a potential collagen-based dressing for wound healing.

Preparation and Characterization of Antibacterial Porcine Acellular Dermal Matrices with High Performance.

Infection is a common complication in the process of wound management. An ideal wound dressing is supposed to reduce or even prevent the infection while promoting wound healing. A porcine acellular dermal matrix (pADM) has been already used as a wound dressing in clinic due to its capacity to accelerate wound healing. However, not only is pure pADM not antibacterial, its mechanical properties are poor. In this study, an antibacterial pADM with good performance was prepared by adding two natural products as modifiers, quercetin (QCT) and tea tree oil (TTO). The result of Fourier-transform infrared (FTIR) proved that the addition of modifiers did not break the natural triple-helical structure of collagen. Meanwhile, the results of differential scanning calorimetry (DSC), thermogravimetric analysis (TG), mechanic experiment, and enzymatic degradation demonstrated that pADM handled with QCT and TTO (termed QCT-TTO-pADM) had better thermal stability, mechanical strength, and resistance to enzymatic degradation than pADM. Meanwhile, QCT-TTO-pADM had excellent antibacterial activity and showed an antibacterial rate of over 80%. Furthermore, in the cytocompatibility analysis, QCT-TTO-pADM had no side effects on the adhesion, growth, and proliferation of fibroblasts. QCT-TTO-pADM could even accelerate wound healing more efficiently than pADM and glutaraldehyde-modified pADM (GA-pADM). In conclusion, QCT-TTO-pADM was a potential antibacterial wound dressing with good performance.

Development of a novel bio-inspired "cotton-like" collagen aggregate/chitin based biomaterial with a biomimetic 3D microstructure for efficient hemostasis and tissue repair.

Hemostatic materials based on collagen and chitin are commonly assessed with regard to their topical absorbability and bioactivity. However, their clinical application faces challenges such as relatively long hemostatic and wound healing times, single function, as well as wound bleeding in patients with blood diseases. Herein, a novel bio-inspired "cotton-like" collagen aggregate/chitin based biomaterial for rapid hemostatic and tissue repair (V-3D-Ag-col) was fabricated by a specific gradient-removal solvent approach. Significantly, for the first time, an advanced collagen aggregate (Ag-col) composed of typical D-periodic cross-striated collagen fibrils and thick collagen fiber bundles was used instead of traditional collagen molecules (Col) to construct a hemostatic material. The target material showed a biomimetic 3D microstructure and "cotton-like" appearance, as expected, which were conducive to platelet adhesion and aggregation. The fabricated V-3D-Ag-col exhibited superior thermo-stability, hemostatic activity and biodegradability. More importantly, V-3D-Ag-col could significantly promote cell growth and proliferation. Further, V-3D-Ag-col could accelerate the wound healing process better than the same material based on conventional collagen (V-3D-Col). In consequence, V-3D-Ag-col has the potential to become a new generation of collagen-absorbable functional hemostatic materials. Furthermore, Ag-col can replace the currently available conventional collagen materials as raw materials for the new generation of collagen-based biomedical materials.

Reinforcement of Polycaprolactone/Chitosan with Nanoclay and Controlled Release of Curcumin for Wound Dressing.

A novel clay-reinforced polycaprolactone/chitosan/curcumin (PCl/CS/Clay/Cur) composite film was fabricated in this study. The prepared Cur-loading composite films were characterized with attenuated total reflection Fourier transformed infrared spectroscopy, scanning electron microscopy, atomic force microscopy, water contact angle, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction, and the results showed good dispersion of clay in the composite films. The addition of nanoclay was found to significantly increase the tensile strength. Also, the clay-enhanced drug-loading films exhibited better controlled-release profiles of Cur than those membranes without clay. Skin disinfection test demonstrated that the curcumin-loaded film could protect wound from bacterial infection. Cytotoxicity analysis proved the good biocompatibility of the composite films. The clay-enhanced Cur-loading films might be promising candidates for wound care.

A novel antibacterial acellular porcine dermal matrix cross-linked with oxidized chitosan oligosaccharide and modified by in situ synthesis of silver nanoparticles for wound healing applications.

Not only are the physicochemical properties and biocompatibility of biomaterials important considerations, but also their antibacterial properties. In this study, a novel chemically-cross-linked antibacterial porcine acellular dermal matrix (pADM) scaffold was fabricated according to a two-step method. A naturally-derived oxidized chitosan oligosaccharide (OCOS) was used to cross-linked pADM (termed OCOS-pADM) to improve its physicochemical properties. Residual aldehyde groups within the OCOS-pADM were used in a redox reaction with Ag ions to produce Ag nanoparticles (AgNPs) in situ. As the AgNPs were tightly adhered onto the scaffold fibrils (termed OCOS-AgNPs-pADM), this effectively functionalized scaffold with antibacterial properties. The generated AgNPs were characterized by UV-Vis diffuse reflectance spectroscopy, XPS and SEM. The results of DSC, TG and enzymatic degradation demonstrated that OCOS-AgNPs-pADM possessed improved thermal stability and resistance to enzymatic degradation compared with pADM scaffolds. The kinetic experiment of the release of silver showed that silver was released in a controllable way. After introducing AgNPs into scaffolds, the OCOS-AgNPs-pADM possessed wide-spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus. Furthermore, MTT assay and CLSM showed that the scaffolds had good biocompatibility. Pieces of OCOS-AgNPs-pADM were implanted into Sprague-Dawley rats to characterize their ability to repair full-thickness skin wounds. And results showed that the OCOS-AgNPs-pADM could accelerate the wound healing process. Overall, this work contributes new insight into the chemical cross-linking and functionalization of pADM scaffolds. In addition, as novel antibacterial scaffolds, OCOS-AgNPs-pADMs have the potential for development as wound dressing materials.

Facile fabrication of gelatin and polycaprolactone based bilayered membranes via spin coating method with antibacterial and cyto-compatible properties.

A growth of bacterial infections and over-and inefficient release of antibiotics forces one to search new antibacterial agents and/or strategies. In this study, a novel strategy towards biocompatible and antibacterial bilayer wound dressing was proposed by a two-step spin coating method combined with in-situ crosslinking polymerization. First, through in-situ crosslinking polymerization, [2-(methacryloyloxy) ethyl] trimethylammonium chloride ([MTA][Cl]) was polymerized and crosslinked in polycaprolactone (PCL) solution and PCL/PMTA solution was obtained. Then, the PCL/PMTA solution was spinning-coated as the antibacterial top layer and the mixture of PCL and gelatin (Gel) (PCL/Gel) as the biocompatible bottom layer. The obvious bi-layered structure and boundary between the two layers was distinctly showed in scanning electron microscope (SEM) pictures. X-ray diffraction (XRD), attenuated total reflection flourier transformed infrared spectroscopy (ATR-FTIR), differential scanning calorimeter (DSC), thermo-gravimetric analysis (TGA) and water contact angle (WCA) analysis were used to investigate the physical and chemical properties and obtained results demonstrated the successful preparation of the bi-layered membranes. The prepared bi-layered wound dressing displayed both strong antibacterial activity and good biocompatibility in vitro. The bilayered membranes with biocompatible and antibacterial properties would be next generation of wound dressing.

Tough and tissue-adhesive polyacrylamide/collagen hydrogel with dopamine-grafted oxidized sodium alginate as crosslinker for cutaneous wound healing.

Natural collagen has good biocompatibility and ability to promote tissue regeneration; however, its low flexibility and easy degradation hinder its applications in wound repair. In this study, we synthesized a skin wound-repairing hydrogel with good bioactivity and high toughness and adhesion. Inspired by the good adhesion of natural mussels, dopamine was grafted onto oxidized sodium alginate to synthesize a new crosslinker (COA), which was introduced into the collagen/polyacrylamide (PAM-Col) double network to synthesize hydrogel. The morphological characterization of the hydrogel using scanning electron microscopy confirmed that the hydrogel formed a more chaotic interconnected structure after the introduction of COA. PAM-Col-COA hydrogel had good mechanical properties, skin tissue adhesion, water absorption, and sustained biological activity. In vivo wound healing experiments showed that hydrogel accelerates the wound healing process and has potential applications in wound dressings.

A novel grapheme oxide-modified collagen-chitosan bio-film for controlled growth factor release in wound healing applications.

Collagen-chitosan composite film modified with grapheme oxide (GO) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), termed CC-G-E film, was loaded with basic fibroblast growth factor (bFGF) as the development of an efficacious wound healing device. In this study we report a novel drug delivery system that prevents the initial burst release and loss of bioactivity of drugs in vitro and in vivo applications. The results showed that CC-G-E film possessed improved thermal stability and a higher rate of crosslinking with increased mechanical properties when the dosage of GO was between 0.03% and 0.07%. It was shown that the in vitro release of bFGF from CC-G-E film continued for more than 28d. Furthermore, the CC-G-E films demonstrated excellent in vitro biocompatibility following culture with L929 fibroblasts in terms of cell adhesion and proliferation. CC-G-E films were implanted into Sprague-Dawley rats to characterize their ability to repair full-thickness skin wounds. Results showed that the CC-G-E film accelerated the wound healing process compared with the blank control. Based on all the results, it was concluded that CC-G-E film operates as a novel drug delivery system and due to its performance in wound remodeling, has potential to be developed as a wound dressing material.