Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Synthesis of chitosan oligosaccharide selenium and its antitumor activity

Background:Polysaccharides have various biological activities;the complexation of polysaccharides with trace element ions can produce synergistic effects,improving the original biological activities of sugars and trace elements.Methods:The preparation process of chitosan oligosaccharide selenium(COSSe)was optimized by the response surface method,followed by a detailed analysis of the resultant compound’s characteristics.The anti-cancer activity of COSSe was studied using the human ovarian cancer cell line SKOV3 as a cell model.Results:The prepared COSSe response surface was well predicted,indicating successful chitosan oligosaccharide binding with selenium.Response surface method analyses identified the optimal synthesis conditions for COSSe:the reaction time of 5.08 h,the reaction temperature of 71.8°C,and mass ratio(Na2SeO3:chitosan oligosaccharide)of 1.02.Under the optimal conditions,the final product,the selenium content,reached 1.302%.The results of cell experiments showed that COSSe significantly inhibited SKOV3 proliferation in a concentration-dependent manner.RNA-seq results showed that chitosan oligosaccharide and COSSe significantly modulated the expression of genes’DNA metabolic processes and cell cycle in SKOV3 cells.Gene enrichment analysis showed the inhibition of the cell cycle,and the results of flow cytometry showed that SKOV3 cells increased in the S phase and decreased in the G2/M phase,with a noted suppression in the protein expression of cyclin-dependent kinase 2(CDK2)and cyclin A1(CCNA1).Conclusion:COSSe has a stronger effect than chitosan oligosaccharide,leading to the arrest of the cell cycle in the S phase.Thus,COSSe may be an effective candidate for the treatment of ovarian cancer.

Chitosan-based triboelectric materials for self-powered sensing at high temperatures

Although biopolymers have been widely utilized as triboelectric materials for the construction of self-powered sensing systems,the annihilation of triboelectric charges at high temperatures restricts the output signals and sensitivity of the assembled sensors.Herein,a novel chitosan/montmorillonite/lignin(CML)composite film was designed and employed as a tribopositive layer in the assembly of a self-powered sensing system for use under hot conditions(25-70℃).The dense contact surface resulting from the strong intermolecular interaction between biopolymers and nanofillers restrained the volatilization of induced electrons.The optimized CML-TENG delivered the highest open-circuit voltage(V_(oc))of 262 V and maximum instantaneous output power of 429 mW/m^(2).Pristine CH-TENG retained only 39%of its initial Voc at 70℃,whereas the optimized CM_(5)L_(3)-TENG retained 66%of its initial Voc.Our work provides a new strategy for suppressing the annihilation of triboelectric charges at high temperatures,thus boosting the development of self-powered sensing devices for application under hot conditions.

Using Electrodeposition of Carboxylated Chitosan for Green Preparation of Copper Nanoclusters and Nanocomposite Films

On the basis of coordinated electrodeposition of carboxylated chitosan(CCS),we presented a green method to prepare Cu NCs and Cu NCs/CCS nanocomposite films.The method shows a range of benefits,such as the convenient and eco-friendly process,mild conditions,and simple post-treatment.The experimental results reveal that a homogeneous deposited film(Cu NCs/CCS nanocomposite film)is generated on the Cu plate(the anode)after electrodeposition,which exhibits an obvious red florescence.The results from TEM observation suggest there are nanoparticles(with the average particle size of 2.3 nm)in the deposited film.Spectral analysis results both demonstrate the existence of Cu NCs in the deposited film.Moreover,the Cu NCs/CCS film modified electrode is directly created through electrodeposition of CCS,which enables promising application in the electrochemical sensing.By means of fluorescence properties of Cu NCs,the Cu NCs/CCS film also owns the potential in fluorescence detection.Therefore,this work builds a novel method for the green synthesis of Cu NCs,meanwhile it offers a convenient and new electrodeposition strategy to prepare polysaccharide-based Cu NCs nanocomposites for uses in functional nanocomposites and bioelectronic devices.

Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.

Chitosan/Sodium Alginate Multilayer pH-Sensitive Films Based on Layer-by-Layer Self-Assembly for Intelligent Packaging

The abuse of plastic food packaging has brought about severe white pollution issues around the world.Developing green and sustainable biomass packaging is an effective way to solve this problem.Hence,a chitosan/sodium alginate-based multilayer film is fabricated via a layer-by-layer(LBL)self-assembly method.With the help of superior interaction between the layers,the multilayer film possesses excellent mechanical properties(with a tensile strength of 50 MPa).Besides,the film displays outstanding water retention property(blocking moisture of 97.56%)and ultraviolet blocking property.Anthocyanin is introduced into the film to detect the food quality since it is one natural plant polyphenol that is sensitive to the pH changes ranging from 1 to 13 in food when spoilage occurs.It is noted that the film is also bacteriostatic which is desired for food packaging.This study describes a simple technique for the development of advanced multifunctional and fully biodegradable food packaging film and it is a sustainable alternative to plastic packaging.

Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.

Smart Colorimetric Corn Starch Films Combined with Anthocyanin-Loaded Glutenin-Carboxymethyl Chitosan Nanocomplexes for Freshness Monitoring of Chilled Pork

In this study,intelligent,pH-responsive colorimetric films were prepared by encapsulating anthocyanins in nanocomplexes prepared from glutenin and carboxymethyl chitosan.These nanocomplexes were added to a corn starch matrix and used in the freshness monitoring of chilled pork.The effects of anthocyanin-loaded nanocomplexes on the physical,structural,and functional characteristics of the films were investigated.The addition of anthocyanin-loaded nanocomplexes increased the tensile strength,elongation at break,hydrophobicity,and light transmittance of the films while decreasing their water vapor permeability.This is because new hydrogen bonds are formed between the film components,resulting in a more homogeneous and dense structure.The colorimetric film has a significant color response to pH changes.These films were used in experiments on the freshness of chilled pork,in which the pH changes with changing freshness states.The results show that the colorimetric film can monitor changes in the freshness of chilled pork in real time,where orange,pink,and green represent the fresh,secondary fresh,and putrefied states of pork,respectively.Therefore,the intelligent colorimetric film developed in this study has good application potential in the food industry.

Adding chitosan nanoparticles of green tea extract in diluent and thawing temperatures ameliorate the post-thawed quality of Boer buck semen

Objective:To improve the quality of post-thawing Boer buck semen for artificial insemination by adding green tea extract chitosan nanoparticles to skimmed egg yolk diluent,and the proper thawing temperature.Methods:The ejaculate of Boer buck was added to skimmed egg yolk diluent without(the control group)and with adding 1μg of chitosan nanoparticles of green tea extract per mL of diluent(the treatment group).Then,the diluted semen was filled in French mini straws containing 60×106 live sperm per straw,frozen in a standard protocol,and stored as frozen semen at−196℃for a week.Six replicates from each group were diluted for 30 s at 37℃or 39℃sterile water to evaluate the semen quality.Results:Post-thawing(at 37℃or 39℃)of live sperm,progressive motility,and plasma membrane integrity were lower compared to those of the pre-freezing stage(P<0.05).Thawing at 37℃resulted in no significant difference in live sperm,progressive motility,and plasma membrane between the control group and the treatment group(P>0.05).The live sperm,progressive motility,and plasma membrane of the treatment group in the pre-freezing stage,and post-thawed at 39℃were higher compared to those of the control group(P<0.05).There was no significant difference in malondialdehyde(MDA)concentration,DNA fragmentation,and catalase concentration of thawing at 37℃compared to those of 39℃in the same group.The MDA concentration and DNA fragmentation in thawing at 37℃and 39℃of the treatment group were significantly lower than those of the control group(P<0.05).However,the catalase concentration in thawing at 37℃and 39℃of the treatment group was not significantly different than the control group(P>0.05).Conclusions:Higher quality post-thawing Boer buck semen is achieved by adding 1μg/mL of chitosan nanoparticles of green tea extract to the skimmed egg yolk diluent and thawing at 39℃.

Extraction, Production and Quality Evaluation of Margarine from Oil Extracted from Waste Biomass Peels of Avocado and Virgin Coconut Oil, Using Chitosan from Reared Shells as Preservative

The production and consumption of avocado pears generates tons of wastes, mainly the pear peels which are usually discarded, although they have been reported to contain important phyto-chemicals with biological activities. The adverse health effect associated with the consumption of saturated lipid based foods has ignited research on reformulation of lipid based foods to eliminate Trans Fatty Acids (TFAs). This study was thus aimed at the extraction and characterization of oil from Avocado Peels (APO) and evaluation of the quality of margarine produced from it. Five verities of pear were used for oil extraction by soxhlet method and physiochemical, oxidative, functional and antioxidant characterization was done. Margarines were formulated using a central composite design using oil blends of APO and Virgin Coconut Oil (VCO) with an oil ratio of 10:90, 40:60, 70:30 respectively, varied blending speed, blending time, and chitosan concentration. Samples were characterized and the effect of process parameters on the physiochemical and functional properties of the margarine studied. Optimized conditions were used to produce samples for sensory evaluation. Color, spreadability, aroma, taste and general acceptability was evaluated using ranking difference test. The results showed that the yield, density, and iodine values of APOs oils ranged from 14.91 ± 0.18 to 11.76 ± 0.46;0.93 ± 0.001 to 0.99 ± 0.1;46.63 ± 1.70 to 52.4 ± 0.63, their acid values, TBA and PV values ranged from 1.42 ± 0.39 to 1.97 ± 0.5;0.11 ± 0.002 to 0.18 ± 0.04;and 2.72 ± 0.14 to 4.43 ± 0.36 respectively, with Brogdon avocado peel variety having the overall best properties prepared blends of trans-free APO margarines showed that increase in APO ratio decreased melting point, increased oxidative stability and reduced moisture content of margarine samples. Chitosan addition leads to decrease moisture content and increase functional properties. VCO lead to increase in phenolic and flavonoid content of the margarines. Samples were spreadable and palatable with R20 being most palatable and the most accepted being R26 with a mean score of 7.07 ± 0.70. Decrease in color intensity increased acceptability. This study therefore demonstrated that avocado peel waste biomass can be valorized by using it as raw material for oil extraction, which can serve as good material for the production of trans-free margarines with good oxidative stability, functional and antioxidant properties.

ZnO Incorporated Acrylamide Grafted Chitosan Based Composite Film for Advanced Wound Healing Applications

This study was carried out to prepare ZnO nanoparticles incorporated acrylamide grafted chitosan composite film for possible biomedical application especially drug loading in wound healing. ZnO nanoparticles were prepared by co-precipitation method from zinc acetate di-hydrate and incorporated in acrylamide grafted chitosan. FT-IR and TGA of the prepared composite film confirmed the successful incorporation of ZnO nanoparticles in the acrylamide-grafted polymer matrix. SEM images showed that the ZnO nanoparticles were homogeneously distributed on the porous matrix of the composite film. Water uptake and buffer uptake analysis revealed that the composite film could hold water and buffer sufficiently, which facilitated the absorption of exudate from the wound site. Amoxicillin was loaded in the prepared composite film and the maximum loading efficiency was found to be 67.33% with drug concentration of 300 ppm. In vitro studies showed greater antimicrobial activity of drug-loaded composite film compared to both pure film and standard antibiotic disc. Finally, the In vivo mouse model showed maximum healing efficiency compared to conventional gauge bandages because the loading of antibiotic in the film produced a synergistic effect and healing time was reduced.

Bactericidal activity of hydrogel beads based on N,N,N-trimethyl chitosan/alginate complexes loaded with silver nanoparticles

Polysaccharide-based composite materials（beads） containing silver nanoparticles（AgNPs） were successfully prepared.Hydrogel beads acted as an efficient vehicle for Ag＊ delivery.Beads promoted the AgNPs protection and inhibited their aggregation.Antimicrobial assays showed that the beads/AgNPs concentration can be modulated to deliver an amount of Ag＊ necessary for kill Escherichia coli cells.

Antibacterial Chitosan-Gelatin Microcapsules Modified with Green-Synthesized Silver Nanoparticles for Food Packaging

Silver nanoparticles(Ag NPs)are an effective antibacterial agent,but their application in food packaging is limited due to their easy agglomeration and oxidation.In this study,antibacterial microcapsules were fabricated using Ginkgo biloba essential oil(GBEO)as core material and chitosan and type B gelatin biopolymer as capsule mate-rials.These antibacterial microcapsules were then modified with green-synthesized Ag NPs,blended into the bio-polymer polylactic acid(PLA),and finally formed as films.Physicochemical properties and antibacterial activity against Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)were evaluated.Results showed that the prepared antibacterial PLA films exhibited excellent antibacterial activity against foodborne pathogens.Its TVC exceeded the limit value of 7 log CFU/g at 7 days compared with the 5 days of pure PLA films.Therefore,these films can extend the shelf life of grass carp fillets by 2–3 days under refrigeration.

Electrodeposition of chitosan/graphene oxide conduit to enhance peripheral nerve regeneration

Currently available commercial nerve guidance conduits have been applied in the repair of peripheral nerve defects.However,a conduit exhibiting good biocompatibility remains to be developed.In this work,a series of chitosan/graphene oxide(GO)films with concentrations of GO varying from 0-1 wt%(collectively referred to as CHGF-n)were prepared by an electrodeposition technique.The effects of CHGF-n on proliferation and adhesion abilities of Schwann cells were evaluated.The results showed that Schwann cells exhibited elongated spindle shapes and upregulated expression of nerve regeneration-related factors such as Krox20(a key myelination factor),Zeb2(essential for Schwann cell differentiation,myelination,and nerve repair),and transforming growth factorβ(a cytokine with regenerative functions).In addition,a nerve guidance conduit with a GO content of 0.25%(CHGFC-0.25)was implanted to repair a 10-mm sciatic nerve defect in rats.The results indicated improvements in sciatic functional index,electrophysiology,and sciatic nerve and gastrocnemius muscle histology compared with the CHGFC-0 group,and similar outcomes to the autograft group.In conclusion,we provide a candidate method for the repair of peripheral nerve defects using free-standing chitosan/GO nerve conduits produced by electrodeposition.

Evaluation of different crosslinking methods in altering the properties of extrusion-printed chitosan-basedmulti-material hydrogel composites

Three-dimensional printing technologies exhibit tremendous potential in the advancing fields of tissue engineering and regenerative medicine due to the precise spatial control over depositing the biomaterial.Despite their widespread utilization and numerous advantages,the development of suitable novel biomaterials for extrusion-based 3D printing of scaffolds that support cell attachment,proliferation,and vascularization remains a challenge.Multi-material composite hydrogels present incredible potential in this field.Thus,in this work,a multi-material composite hydrogel with a promising formulation of chitosan/gelatin functionalized with egg white was developed,which provides good printability and shape fidelity.In addition,a series of comparative analyses of different crosslinking agents and processes based on tripolyphosphate(TPP),genipin(GP),and glutaraldehyde(GTA)were investigated and compared to select the ideal crosslinking strategy to enhance the physicochemical and biological properties of the fabricated scaffolds.All of the results indicate that the composite hydrogel and the resulting scaffolds utilizing TPP crosslinking have great potential in tissue engineering,especially for supporting neo-vessel growth into the scaffold and promoting angiogenesis within engineered tissues.

Chitosan derived carbon membranes as protective layers on zinc anodes for aqueous zinc batteries

Aqueous zinc batteries with low cost and inherent safety are considered to be the most promising energy storage devices.However,they suffer from poor cycling stability and low coulombic efficiencies caused by the adverse zinc dendrites on the anodes during the discharging/charging processes.Chitosan is a kind of natural amino polysaccharide,which is rich in nitrogen and carbon.When sintered at high temperatures,carbon membranes have been achieved with excellent conductivity and graphitization degree,which could enhance the ability to induce zinc ion uniform deposition to some extent.In this work,a type of carbon membrane using chitosan as raw materials has been fabricated by sintering,and then assembled as the protect layers in aqueous zinc batteries.The results show that the samples could retain smoother surfaces when adopting the sintering temperature of 800℃,and the assembled batteries are able to achieve about 700 h at a current density of 0.25m A·cm^(-2),which is far longer than those of the similar batteries without any carbon membranes.

Environmentally Friendly Chitosan-Based Wood/Wood Composite Adhesive: Review

Due to the world’s energy issues and dependency on petroleum resources, focus has switched to finding new, sustainable raw material sources for wood adhesives. Renewable biopolymers would gradually replace petroleum and natural gas as the primary raw materials used in wood adhesives. Chitosan is a biomass substance having a lot of reserves. Chitosan is one of the most fascinating biopolymers in the adhesive sector because of its potential qualities for adhesive applications, such as biodegradability, biocompatibility, and non-toxicity. Chitosan and its derivatives have so garnered considerable interest in a wide range of adhesive applications. However, its adhesive strength is insufficient to glue wood under normal, humid conditions. There has been a lot of study done on how to make chitosan-based adhesives more cohesive and water resistant. In order to effectively use chitosan-based wood glue in wood/wood composite adhesive that gives comparable performance to synthetic adhesives, numerous new ways have been developed. It has been modified by the addition of various cross-linkers, including aldehydes like glyoxal glutaraldehyde etc., epoxy compounds, blended with other polymers, different acids and chitosan grafted onto vinyl acetate. In the production of wood composites, chitosan can also scavenge formaldehyde. This review of chitosan-based adhesives focuses on various cross-linkers for chitosan modification in order to improve the properties of chitosan-based wood adhesives.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury

There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Fabrication of chitosan/silica hybrid coating on AZ31 Mg alloy for orthopaedic applications

Biocompatible conversion of chitosan and chitosan/silica hybrid coating were prepared to enhance the biocompatibility and corrosion resistance of biodegradable AZ31 Mg alloy. The coatings were optimized and analysed with potentiodynamic polarization, SEM, ATR-IR and XPS studies. Potentiodynamic polarization studies, revealed that the coatings exhibited high corrosion resistance. The surface morphology of the Ch-3/Si coating showed small globular rough structure. The presence of functional groups was confirmed by ATR-IR. For a better understanding of chitosan/silica hybrid coating, the chemical states were examined by XPS studies. The in-vitro bioactivity of the coated samples was evaluated in Earle’s solution, which formed a dense layer of coral-like structure and calcium-deficient apatite with less stoichiometric ratio than the hydroxyapatite. In-vitro cell culture studies exhibited a good cell proliferation rate and the fabricated Ch-3/Si coating was found to be non-hemolytic. The bacterial studies proved that Ch-3/Si coating possessed inherent antibacterial activity.

Chitosan conduits enriched with fibrin-collagen hydrogel with or without adipose-derived mesenchymal stem cells for the repair of 15-mm-long sciatic nerve defect

Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.