Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

Increasing evidence indicates that engineered nerve grafts have great potential for the regeneration of peripheral nerve injuries(PNIs).While most studies have focused only on the topographical features of the grafts,we have considered both the biophysical and biochemical manipulations in our applied nanoscaffold.To achieve this,we fabricated an electrospun nanofibrous scaffold(ENS)containing polylactide nanofibers loaded with lithium(Li)ions,a Wnt/β-catenin signaling activator.In addition,we seeded human adipose-derived mesenchymal stem cells(hADMSCs)onto this engineered scaffold to examine if their differentiation toward Schwann-like cells was induced.We further examined the efficacy of the scaffolds for nerve regeneration in vivo via grafting in a PNI rat model.Our results showed that Li-loaded ENSs gradually released Li within 11 d,at concentrations ranging from 0.02 to(3.64±0.10)mmol/L,and upregulated the expression of Wnt/β-catenin target genes(cyclinD1 and c-Myc)as well as those of Schwann cell markers(growth-associated protein 43(GAP43),S100 calcium binding protein B(S100B),glial fibrillary acidic protein(GFAP),and SRY-box transcription factor 10(SOX10))in differentiated hADMSCs.In the PNI rat model,implantation of Li-loaded ENSs with/without cells improved behavioral features such as sensory and motor functions as well as the electrophysiological characteristics of the injured nerve.This improved function was further validated by histological analysis of sciatic nerves grafted with Li-loaded ENSs,which showed no fibrous connective tissue but enhanced organized myelinated axons.The potential of Li-loaded ENSs in promoting Schwann cell differentiation of hADMSCs and axonal regeneration of injured sciatic nerves suggests their potential for application in peripheral nerve tissue engineering.

Preparation of polypyrrole-embedded electrospun poly(lactic acid) nanofibrous scaffolds for nerve tissue engineering

Polypyrrole （PPy） is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We embedded PPy into poly（lactic acid） （PLA） nanofibers via electrospinning and fabricated a PLA/PPy nanofibrous scaffold containing 15% PPy with sustained conductivity and aligned topog- raphy, qhere was good biocompatibility between the scaffold and human umbilical cord mesenchymal stem cells as well as Schwann cells. Additionally, the direction of cell elongation on the scaffold was parallel to the direction of fibers. Our findings suggest that the aligned PLA/PPy nanofibrous scaffold is a promising biomaterial for peripheral nerve regeneration.

Nanofibrous scaffolds for the regeneration of nervous tissue

Introductons The biophysical organization of extracellular matrix (ECM) plays an important role in tissue morphogenesis,remodeling and functions. In many types of tissues,e. g. ,blood vessel,nerve,heart,muscle,tendon and ligament,ECM has aniso-

VE TPGS-Loaded Silk Fibroin / Hydroxybutyl Chitosan Nanofibrous Scaffolds for Skin Care Application

Vitamin E( VE) is an ideal antioxidant and a stabilizing agent in biological membranes. In this study,silk fibroin( SF) /hydroxybutyl chitosan( HBC) nanofibrous scaffolds are loaded with VE tocopherol polyethylene glycol 1000 succinate( VE TPGS) via electrospinning. SEM images show that the average nanofibrous diameter has no significant difference when the content of VE TPGS increases to 4. 0%( SF / HBC). However,the average nanofibrous diameter decreases largely to 200 nm when the VE TPGS content reaches 6. 0%. Furthermore,VE TPGS presents a sustained release behavior from the nanofibrous scaffolds. Cell viability studies of mouse skin fibroblasts( L929) demonstrate that VE TPGS loaded SF / HBC nanofibrous scaffolds present good cellular compatibility.Moreover,the incorporation of VE TPGS could strengthen the ability of SF / HBC nanofibrous scaffolds on protecting the cells against oxidation stress using the Tertbutyl hydroperoxide( t-BHP)-induced oxidative injury model. Therefore,VE TPGS-loaded SF /HBC nanofibrous scaffolds might be potential candidates for personal skin care,wound dressing and skin tissue engineering scaffolds.

Adipose tissue-derived mesenchymal stem cells and chitosan/poly(vinyl alcohol)nanofibrous scaffolds for cartilage tissue engineering

Osteoarthritis(OA)has been defined as a chronic inflammatory joint disease characterized by progressive articular cartilage degeneration.Recently growing interest in regenerative medicine,using cell therapy and tissue engineering,where cellular components in combination with engineered scaffolds and bioactive materials were used to induce functional tissue regeneration.In the present study,nanofibrous scaffold based on chitosan(CS)/poly(vinyl alcohol)(PVA)were used to develop biologically functionalized biomaterial to mimic the extracellular matrix,allowing the human adipose tissue derived mesenchymal stem cells(ADSCs)to proliferate and differentiate to chondrogenic cells.The morphology of the nanofibrous mat was examined using field emission scanning electron microscope(FE/SEM).The characteristic functional groups and the nature of the chemical bonds between atoms were evaluated using Fourier transform infrared spectroscopy(FTIR)spectrum.Characterization of the seeded cells was morphologically evaluated by scanning electron microscopy and by flow cytometry for the expression of the stem cell surface markers.The differentiation potential was verified after chondrogenic induction by analyzing the expression of chondrogenic marker genes using real-time(RT PCR).Current study suggest significant potential for the use of ADSCs with the nanofibrous scaffolds in improving the osteoarthritis pathology.

Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor

Currently,more and more patients suffer from peripheral nerve injury due to trauma,tumor and other causes worldwide.Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury.However,an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms.In this work,aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes(MWCNTs)were fabricated via coaxial electrospinning,and nerve growth factor(NGF)and Lycium barbarum polysaccharides(LBP)purified from the wolfberry were loaded on the core and shell layers of the nanofibers,respectively.LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury.In addition,the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated.MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity,which promoted the directional growth and neurite extension of neurons in vitro.Further,the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons.Based on robust cell-induced behaviors,conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery.

Fabrication of glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)-polyethylene glycol diacrylate hybrid 3D nanofibrous scaffolds for tissue engineering

In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration,a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)–polyethylene glycol diacrylate(SFMA/P(LLA-CL)–PEGDA)hybrid three-dimensional(3D)nanofibrous scaffolds was successfully fabricated through the combination of 3D nanofibrous platforms and divinyl PEGDA based photocrosslinking,and then further improved water resistance by ethanol vapor post-treatment.Scanning electron microscopy and micro-computed tomography results demonstrated significant PEGDA hydrogel-like matrices bonded nanofibers,which formed a 3D structure similar to that of“steel bar(nanofibers)‒cement(PEGDA)”,with proper pore size,high porosity,and high pore connectivity density.Meanwhile,the hybrid 3D nanofibrous scaffolds showed outstanding swelling properties as well as improved compressive and tensile properties.Furthermore,these hybrid 3D nanofibrous scaffolds could provide a biocompatible microenvironment,capable of inducing the material‒cell hybrid and regulating human umbilical vein endothelial cells proliferation.They thus present significant potential in tissue regeneration.

Fabrication and characterization of curcumin-loaded silk fibroin/P（LLA-CL） nanofibrous scaffold

Curcumin exhibited excellent properties including antioxidant, anti- inflammatory, antiviral, antibacterial, antifungal, anticancer, and anticoagulant activities. In this study, curcumin was incorporated into silk fibroin （SF）/poly（L-lactic acid-co-e- caprolactone） （P（LLA-CL）） nanofibrous scaffolds via electrospinning, and changes brought about by raising the curcumin content were observed： SEM images showed that the average nanofibrous diameter decreased at the beginning and then increased, and the nanofibers became uniform; FTIR showed that the conformation of SF transforming from random coil form to β-sheet structure had not been induced, while SF conformation converted to β-sheet after being treated with 75% ethanol vapor; XRD results confirmed that the crystal structure of （P（LLA-CL）） had been destroyed; The mechanical test illustrated that nanofibrous scaffolds still maintained good mechanical properties. Further, curcumin-loaded nanofibrous scaffolds were evaluated for drug release, antioxidant and antimicrobial activities in vitro. The results showed that curcumin presented a sustained release behavior from nanofibrous scaffolds and maintained its free radical scavenging ability, and such scaffolds could effectively inhibit S. aureus growth （〉 95%）. Thus, curcumin-loaded SF/P（LLA-CL） nanofibrous scaffolds might be potential candidates for wound dressing and tissue engineering scaffolds.

Prussian blue and collagen loaded chitosan nanofibers with NIR-controlled NO release and photothermal activities for wound healing

Nitric oxide(NO)has emerged as a potential wound therapeutic agent due to its pivotal role in the wound healing processes.Nevertheless,NO-based therapy for clinical applications is still restricted due to its gaseous state and short half-life.Here we exploited a wound dressing by incorporating sodium nitroprusside doped prussian blue nanoparticals and Type I collagen into the chitosan/poly(vinyl alcohol)nanofibers through the electrospinning method.This hybrid nanofibrous scaffold possess the excellent abilities of NIR controlled NO release,photothermal therapy,and imitation of extra-cellular matrix-like architecture.These synergistic effects could enhance their anti-bactericidal effects in vitro and furthermore accelerate wound healing in vivo when compared to control groups.Histological analysis demonstrated the scaffold could promote fibroblast growth and accelerate epithelialization.Moreover,no apparent histological toxicology and negligible damage to major organs were observed,which provided sufficient biosafety for in vivo application.These data indicate the fabricated hybrid nanofibrous scaffold could be used as an ideal candidate for accelerating wound healing and treating chronic wounds.