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1.
New blood vessel formation is an essential part of wound healing to provide cells with the nutrients and oxygen for their survival. Many nonhealing ulcers fail to heal because of poor blood supply and skin grafts will also fail to take on poorly vascularized wound beds. There is a real need for proangiogenic biomaterials to assist wound healing. In vivo heparin binds proangiogenic growth factors and helps regulate new blood vessel formation, hence heparin containing biomaterials are attractive. To achieve a hydrogel with high heparin binding capacity a composite of chitosan, poly(vinyl alcohol) (PVA) and polycaprolactone (PCL) was produced. Chitosan is a biodegradable natural polymer with great potential for biomedical applications due to its biocompatibility, high charge density and nontoxicity. PVA is biocompatible and nontoxic with good chemical stability, film-forming ability, and high hydrophilicity. PCL has physicochemical and mechanical properties comparable to those of the biological tissues and due its hydrophilic nature helps in the sustained release of drugs. Accordingly in this study we explored a range of PCL concentrations from 4% to 16% added to hydrogels composed of chitosan and PVA. Heparin was blended into the polymer mixture and the nanoporous structure was created by freeze-drying the PCL hydrogel. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR) and XPS confirmed the presence of sulfur on the surface of the hydrogels. Their porous morphology was investigated by scanning electron microscope (SEM). The Chick Chorionic Allantoic Membrane (CAM) assay was used to study the angiogenic potential of these materials and histology (H&E and Goldner trochome) was used to confirm the presence of new blood vessels inside the hydrogels. We report that the addition of 8% PCL to the hydrogels gave porous structures containing heparin, which significantly increased new blood vessel formation into the hydrogels. These hydrogels offer a new approach to biomaterials, which could be added to wounds to improve vascularization.  相似文献   

2.
Here we report a novel, fast, and facile sythesis of chitosan-based hydrogels by ethanol directly inducing. In the present of ethanol, chitosan (CS) with glutaric anhydride (GA) could form hydrogels (CS-GA-Hs) just in few minutes. The results of 1H NMR and FTIR confirmed N-acylation substitution of chitosan. Furthermore, the relative concentration of GA was also the critical parameter for formation and properties of CS-GA-Hs. When the concentration was 1.5, CS-GA-Hs showed the highest swelling (253.6%) and release degree (99.9%). The porous structure of CS-GA-Hs were observed by SEM and the pore size of the gels decreased from 500 to 200 μm, when the relative concentration of GA was changed from 1.5 to 4. And all the hydrogels were demonstrated a good mechanical properties. Additionally, the CS-GA-Hs showed in vitro antimicrobial activity against Staphylococcus aureus and Escherichia coli, and no cytotoxicity toward L929 mouse fibroblasts, meaning it has potential applications in biomedical fields.  相似文献   

3.
Chitosan polymer as a bioactive carrier has an emerging importance due to its great versatility. Many strategies are reported for enhancing its properties. Herein, chitosan hydrogels modified by dodecenylsuccinic anhydride (DDSA) are prepared, characterized by SEM, FTIR, 13C NMR while their mechanical properties and cytotoxicity are assessed. Chitosan modification was studied by FTIR and 13C NMR. According to rheological measurements, modified chitosan hydrogels present a predominantly elastic behavior and exert a higher compressive strength than chitosan hydrogels. Furthermore, this work evaluates thymol incorporation, its release profile as well as its in vivo performance in a periodontitis rat model. In vitro studies reveal that thymol-loaded-DDSA-chitosan hydrogels possess antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa for 2 days and antioxidant activity for 5 days. The incorporation of hydrophobic chains improves thymol release profile; however, DDSA-chitosan hydrogels cytotoxicity is greater when compared to chitosan hydrogels. Finally, in a preliminary in vivo study, the local application of thymol-loaded hydrogels is evaluated during a one-week period. The histomorphometric measurements indicate that periodontal damage is lower when thymol is administrated in chitosan hydrogels in comparison to DDSA-chitosan hydrogels. Nevertheless, DDSA-chitosan hydrogels could still be useful for the sustained local delivery of hydrophobic drugs.  相似文献   

4.
A new family of cationic hybrid hydrogels from two new positively charged aqueous soluble precursors, glycidyl methacrylate‐chitosan (GMA‐chitosan), and 2‐(acryloyloxy) ethyl trimethylammonium (AETA), was developed via a simple photocrosslinking fabrication method. These hybrid hydrogels have pendant quaternary ammonium functional groups on the AETA segments. The chemical composition of GMA‐chitosan/AETA hybrid hydrogels were characterized by Fourier transform infrared spectroscopy and their mechanical, swelling, and morphological properties were examined as a function of the composition of the hybrids as well as the effect of pH and ionic strength of the surrounding medium. GMA‐chitosan/AETA hybrid hydrogels show a porous network structure with average pore diameter 20–50 μm. The compression moduli of these hybrid hydrogels ranged from 27.24 to 28.94 kPa, which are significantly higher than a pure GMA‐chitosan (17.64 kPa). GMA‐chitosan/AETA hybrid hydrogel shows pH/ionic strength responsive swelling behavior because of the presence of the positive charge pendant groups. These hybrid hydrogels showed a sustained BSA protein release and a significantly lower initial burst release than a pure GMA‐chitosan hydrogel. The two aqueous soluble precursors and the cationic charge characteristics of the resulting GMA‐chitosan/AETA hybrid hydrogels may suggest that this new family of biomaterials may have promising applications as the pH responsive protein drug delivery vehicles. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3736–3745, 2013  相似文献   

5.
Abstract

Tissue engineering provides alternative solutions to traditional transplantation. In this study a novel strategy of chitosan scaffolds obtainment based on selective O-crosslinking using Aspartic acid and the addition of TiO2 nanoparticles is presented. Prepared under microwave conditions biomaterials were of increased mechanical and thermal durability thanks to NPs presence comparing to pure chitosan. Moreover porous scaffolds maintained antimicrobial activity against S. Aureus and E. Coli. Biomaterials were susceptible to in vitro biodegradation and degradation. Hydrogels exhibited positive impact on proliferation activity of fibroblasts. Thus they may be applied as 3D scaffolds in tissue engineering focused on wound healing.  相似文献   

6.
Chitosan‐based hydrogels are considered as promising biomaterials for tissue engineering. Biological properties of chitosan could be significantly improved by modification of its chemical structure. This study was aimed at characterizing macroporous hydrogels fabricated by freeze‐drying technique from chitosan, which has been N‐acetylated by 2,2‐bis(hydroxymethyl)propionic acid or l ,d ‐lactide. The nature of the acetylated agent was shown to significantly affect hydrogels morphology, swelling behavior, zeta‐potential, and protein sorption as well as their degradation by lysozyme. According to scanning electron and confocal laser scanning microscopy, the hydrogels possessed interconnected macroporous network that facilitated cells penetration into the interior regions of the hydrogel. Chemical modification of chitosan significantly influenced L929 cell growth behavior on hydrogel compared to the non‐modified chitosan. The proposed chemical strategy for modification of chitosan could be considered as promising approach for improvement of chitosan hydrogels. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44651.  相似文献   

7.
A series of novel hydrogels based on carboxymethyl chitosan (CMCS) has been synthesized by a cross-linking reaction between CMCS and various amounts of N,N′-bis [4-(isothiocyanate carbonyl)phenyl] pyromellitimide as a cross-linker to produce pyromellitimide benzoyl thiourea–CMCS hydrogels designated as PIBTU–CMCS (1–4). Hydrogel structures were identified by elemental analyses and FTIR and 1H-NMR spectroscopy. The prepared hydrogels were characterized for their properties to understand the influence exerted by controlled structural variations in these hydrogels. All the hydrogels showed a greater antibacterial activity on Gram-positive than Gram-negative bacteria. They also exhibited higher antifungal activities. Their antimicrobial activity improved by increasing their cross-linking degree.  相似文献   

8.
Composite chitosan/active carbon (AC) hydrogels were elaborated by a novel route, consisting in exposing the chitosan solution to ammonia vapors. This vapor‐induced gelation method was compared with the conventional elaboration process, a direct immersion of the chitosan solution in liquid ammonia. The hydrogels were characterized to evaluate their potential application as wound‐dressings, mostly regarding their morphology, mechanical properties, swelling behavior, and sorption capacities for malodorous compounds emitted from wounds as diethylamine (DEA). The influence of elaboration route, chitosan concentration, and AC incorporation was studied. The results show that freeze‐dried hydrogels have a porous asymmetric structure dependent on the chitosan concentration and which promotes exudates drainage. The nanostructure of the parent hydrogel is semi‐crystalline and slightly dependent on the gelation conditions. It confers on hydrogel an acceptable mechanical behavior (compressive modulus up to 1.08·105 Pa). Hydrogels including AC display enhanced sorption kinetics for DEA, with sorption capacities up to 49 mg g?1. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013  相似文献   

9.
Hydrogels constructed from naturally derived polymers provide an aqueous environment that encourages cell growth, however, mechanical properties are poor and degradation can be difficult to predict. Whilst, synthetic hydrogels exhibit some improved mechanical properties, these materials lack biochemical cues for cells growing and have limited biodegradation. To produce hydrogels that support 3D cell cultures to form tissue mimics, materials must exhibit appropriate biological and mechanical properties. In this study, novel organic-inorganic hybrid hydrogels based on chitosan and silica were prepared using the sol-gel technique. The chemical, physical and biological properties of the hydrogels were assessed. Statistical analysis was performed using One-Way ANOVAs and independent-sample t-tests. Fourier transform infrared spectroscopy showed characteristic absorption bands including amide II, Si-O and Si-O-Si confirming formation of hybrid networks. Oscillatory rheometry was used to characterise the sol to gel transition and viscoelastic behaviour of hydrogels. Furthermore, in vitro degradation revealed both chitosan and silica were released over 21 days. The hydrogels exhibited high loading efficiency as total protein loading was released in a week. There were significant differences between TC2G and C2G at all-time points (p < 0.05). The viability of osteoblasts seeded on, and encapsulated within, the hydrogels was >70% over 168 h culture and antimicrobial activity was demonstrated against Pseudomonas aeruginosa and Enterococcus faecalis. The hydrogels developed here offer alternatives for biopolymer hydrogels for biomedical use, including for application in drug/cell delivery and for bone tissue engineering.  相似文献   

10.
A new biomaterial, a hydrogel, with dual-crosslinked design, has been created with enhanced mechanical performance. The hydrogels are fabricated based on water-soluble chitosan, with dual-crosslinking of imine linkages and host–guest interactions. Phenolphthalein-grafted N-carboxyethyl chitosan (CECS-g-PHP), as a guest polymer, is synthesized and structurally characterized and complexed with hexamethylenediamine modified β-cyclodextrin (β-CD-HDA), as a host molecule. Oxidized sodium alginate (OSA) is added to form crosslinking networks via imine linkages with the existing amino groups. The hydrogels show significantly shorter gelation times and higher compressive stresses, compared with single-crosslinked hydrogels. The phenolphthalein units in the hydrogel change color with pH and other added chemicals. Moreover, the hydrogels can be injected and are self-healing with >80% recovery within 4 h. Thus, these dual-crosslinked hydrogels, which respond to pH and other stimuli, are promising designs for new multifunctional biomaterials.  相似文献   

11.
Articular cartilage has poor ability to heal once damaged. Tissue engineering with scaffolds of polymer hydrogels is promising for cartilage regeneration and repair. Polymer hydrogels composed of highly hydrated crosslinked networks mimic the collagen networks of the cartilage extracellular matrix and thus are employed as inserts at cartilage defects not only to temporarily relieve the pain but also to support chondrocyte proliferation and neocartilage regeneration. The biocompatibility, biofunctionality, mechanical properties, and degradation of the polymer hydrogels are the most important parameters for hydrogel‐based cartilage tissue engineering. Degradable biopolymers with natural origin have been widely used as biomaterials for tissue engineering because of their outstanding biocompatibility, low immunological response, low cytotoxicity, and excellent capability to promote cell adhesion, proliferation, and regeneration of new tissues. This review covers several important natural proteins (collagen, gelatin, fibroin, and fibrin) and polysaccharides (chitosan, hyaluronan, alginate and agarose) widely used as hydrogels for articular cartilage tissue engineering. The mechanical properties, structures, modification, and structure–performance relationship of these hydrogels are discussed since the chemical structures and physical properties dictate the in vivo performance and applications of polymer hydrogels for articular cartilage regeneration and repair. © 2012 Society of Chemical Industry  相似文献   

12.
An easy and ecofriendly method for designing double‐network (DN) hydrogels based on chitosan and poly(vinyl alcohol) (PVA) with high mechanical performance is described. When covalent bonds in the networks are used as crosslinking agents in the achievement of a higher mechanical strength, the irreversible deformation of these hydrogels after a large force is applied is still one of the most important obstacles. To overcome this problem, we used physical crosslinking for both networks. The mechanical strength, surface morphology, and cytotoxicity of the films were studied by tensile testing, scanning electron microscopy analysis, and an MTT assay. The synthesized chitosan–PVA DN hydrogels showed a large improvement in the tensile strength to 11.52 MPa with an elongation of 265.6%. The surface morphologies of the films demonstrated the effective interactions between the two networks and a suitable porosity. Also, because of the use of a natural polymer and honey as a plasticizer, the cell culture indicated that the synthesized DN hydrogels had good biocompatibility (with 327.49 ± 11.22% viability) and could be used as capable biomaterials. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45752.  相似文献   

13.
Gelatin/chitosan hydrogels were prepared by using glutaraldehyde as crosslinker. The porous structure was confirmed by scanning electron microscope (SEM). Swelling ratios of the hydrogels with various ratio of gelatin to chitosan and crosslinker reagent dosage were studied in phosphate-buffered saline (PBS). In addition, in-vitro cytotoxicity was assessed via MTT assay with fibroblastic cell cultured in hydrogel extractions. It was found that by increasing glutaraldehyde dosage and chitosan content, the swelling ratio of the hydrogels decreased in buffer solutions. The MTT test showed that the gelatin/chitosan hydrogel clearly presented adequate cell viability, non-toxicity, and suitable properties. Therefore, these developed blends, based on gelatin and chitosan has broadened the number of choices of biomaterials to be potentially used in biomedical applications such as biomaterial, drug delivery vehicles and skin tissue engineering.  相似文献   

14.
Chitosan has received extensive attention as a biomedical material; however, the poor solubility of chitosan is the major limiting factor in its utilization. In this study, chitosan‐based biomaterials with improved aqueous solubility were synthesized. Two molecular weights (750 Da and 2000 Da) of methoxypoly(ethylene glycol) (mPEG) were grafted onto chitosan (mPEG‐g‐chitosan) to form a ~100‐μm‐thick plastic film as a wound dressing. The chemical structures of the mPEG‐g‐chitosan copolymers were confirmed using Fourier transform infrared spectroscopy (FTIR), and the thermal properties were characterized using thermogravimetry analysis (TGA). Their microstructures were observed using scanning electron microscopy (SEM). The other properties were analyzed via the swelling ratio, tensile strength, elongation, and water vapor transmission rate (WVTR). Biocompatibility evaluations through biodegradability, cytotoxicity, and antimicrobial effect studies were also performed. The obtained mPEG‐g‐chitosan copolymers were soluble in slightly acidic aqueous solutions (pH~6.5) at a concentration of 10 wt %. The optimal mPEG‐g‐chitosan hydrogels had swelling ratios greater than 100% and WVTRs greater than 2000 g/m2/day. Their performance against Staphylococcus aureus will be subjected to further improvements with respect to medical applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42340.  相似文献   

15.
Star‐shaped polycaprolactone (stPCL)/chitosan composite hydrogel was fabricated by simply melt/solution blending between chitosan/dicarboxylic acid solution and melted stPCL, using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride and N‐hydroxysuccinimide as conjugating agents to obtain a composite hydrogel. Here, stPCL and modified stPCL were investigated. The stPCL was modified to have a carboxyl‐terminated chain (stPCL‐COOH). The composite hydrogels were transparent. The network structure of the composite hydrogels was investigated. stPCL‐OH had no chemical bond to the chitosan network but stPCL‐COOH could co‐crosslink with the chitosan network. The porous structure and porosity of the composite hydrogels were similar to those of chitosan hydrogel. However, the hydrophobicity of stPCL resulted in a lower swelling ratio compared to chitosan hydrogel. The rheological analysis of the composite hydrogel exhibited a stable crosslinked network. Compression testing of the composite hydrogel obtained from stPCL‐COOH at a mole ratio of stPCL‐COOH and chitosan of 1:1 had optimum compressive mechanical properties comparable to chitosan hydrogel due to a synergistic effect of the flexibility in stPCL and the co‐crosslinking of stPCL‐COOH with the chitosan network. © 2020 Society of Chemical Industry  相似文献   

16.
Composite materials based on carbon nanotubes (CNT) and polymeric hydrogels have become the subject matter of major interest for use as carriers in drug delivery research. The aim of this study was to evaluate the in vitro cytotoxicity of the hydrogel–carbon nanotube–chitosan (hydrogel–CNT–CH) composites on intestinal cells. Oxidized CNT were wrapped with chitosan (CH), Fourier transform infrared (FT‐IR) analysis suggest that oxidized CNT interact with CH. Transmission electron microscopy (TEM) images show a CH layer lying around CNT. Chitosan wrapped CNT were incorporated to poly (acrylamide‐co‐acrylic acid) hydrogels. Swelling behavior in buffers at different pH were evaluated and revealed a significantly lower swelling when it is exposed to a acid buffer solution (pH 2.2). Mechanical properties were evaluated by measurements of elasticity and the material with CNT showed better mechanical properties. The incorporation and liberation of Egg Yolk Immunoglobulin from hydrogel–CNT–CH were also assessed and it revealed an improved performance. To evaluate the effect of these nanocomposites on cellular redox balance, intestinal cells were exposed to hydrogel–CNT–CH composites and antioxidant enzymes were assessed. Cytotoxicity and apoptosis were also evaluated. Hydrogel–CNT–CH composites induce no oxidative stress and there were no evidence of cytotoxicity or cell death. These preliminary findings suggest that hydrogel–CNT–CH composites show improved properties and good biocompatibility in vitro making these biomaterials promising systems for drug delivery purposes. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41370.  相似文献   

17.
Resistance to nonspecific protein adsorption and the capability to provide targeted bioactive signals are essential qualities for implantable biomaterials. The development of materials that combine these multifunctional characteristics and tunable mechanical properties has been a target in the tissue engineering field over the last decade. This study is the first to demonstrate that polyampholyte hydrogels prepared with equimolar quantities of positively charged and negatively charged monomer subunits from multiple monomer compositions have great potential to address these needs. The hydrogels were synthesized with positively charged [2‐(acryloyloxy)ethyl] trimethylammonium chloride and different monomer ratios of the negatively charged 2‐carboxyethyl acrylate and 3‐sulfopropyl methacrylate monomers. The physical and chemical properties of the hydrogels were fully characterized, including swelling, hydration, mechanical strength, and chemical composition, and the fouling resistance of the hydrogels was demonstrated using enzyme‐linked immunosorbent assays. Additionally, the capability of the hydrogels to facilitate protein conjugation via EDC/NHS conjugation chemistry was assessed. The results clearly demonstrate that the polyampholyte hydrogels have a range of tunable mechanical strength based on the monomer subunits, while maintaining their excellent nonfouling properties. Additionally, high levels of conjugated protein were achieved for all of the monomer combinations investigated. Therefore, the broadly applicable multifunctional properties of polyampholyte hydrogels and their tunable mechanical properties clearly demonstrate the potential of these materials for tissue engineering. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43985.  相似文献   

18.
Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry  相似文献   

19.
Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. In the present investigation blends of chitosan and gelatin with various compositions were produced as candidate materials for biomedical applications. Fourier transform infrared spectral analysis showed good compatibility between these two biodegradable polymers. The composite films showed improved tensile properties, highly porous structure, antimicrobial activities, low water dissolution, low water uptake and high buffer uptake compared to pure chitosan or gelatin films. These enhanced properties could be explained by the introduction of free ? OH, ? NH2 and ? NHOCOCH3 groups of the amorphous chitosan in the blends and a network structure through electrostatic interactions between the ammonium ions (? NH3+) of the chitosan and the carboxylate ions (? COO?) of the gelatin. Scanning electron microscopy images of the blend composite films showed homogeneous and smooth surfaces which indicate good miscibility between gelatin and chitosan. The leafy morphologies of the scaffolds indicate a large and homogeneous porous structure, which would cause increased ion diffusion into the gel that could lead to an increase in stability in aqueous solution, buffer and temperature compared to the gelatin/chitosan system. In vivo testing was done in a Wistar rat (Rattus norvegicus) model and the healing efficiencies of the scaffolds containing various compositions of chitosan were measured. The healing efficiencies in Wistar rat of composites with gelatin to chitosan ratios of 10:3 and 10:4 were compared with that of a commercially available scaffold (Eco‐plast). It was observed that, after 5 days of application, the scaffold with a gelatin to chitosan ratio of 10:3 showed 100% healing in the Wistar rat; however, the commercial Eco‐plast showed only a little above 40% healing of the dissected rat wound. Copyright © 2012 Society of Chemical Industry  相似文献   

20.
Hydrogels can be one of the best polymeric wound dressings due to the desirable properties of wound healing. In this study, emphasizing the use of natural biomaterials such as Aloe vera and honey in the structure of cross-linked polymers, a novel hydrogel was produced that might be applied to healing wounds. In the beginning, four hydrogel groups were made from a combination of Sodium Alginate and Chitosan with Aloe vera extract and honey in optimum concentrations. Then the structure of those was evaluated by SEM and FTIR. After confirming hydrogels' structural properties, their physical properties, including swelling, porosity, density, mass loss, stability, and WVTR, were examined. Besides, the hydrogel biocompatibility was assessed by analyzing the cell viability and hemolytic activity. Adhesion of the cells to the hydrogel was also observed by SEM imaging. The results showed that the designed hydrogel has a porous structure with interconnected cavities, which their size can provide suitable conditions for cell adhesion, migration, and proliferation. Also, their physical and structural properties can be a strong suit to wound healing. Although honey's application can weaken the hydrogel structure, honey has beneficial properties due to its complex biomolecules. In contrast, Aloe vera in hydrogel generally improved the hydrogel's specificity for wound healing. According to the results of this study, taking advantage of hydrogels containing honey and Aloe vera based on alginate and chitosan polymers led to the formation of an acceptable structure and biocompatibility that can be used in future researches to repair tissues, especially wounds.  相似文献   

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