Biodegradable Composite Nanofibers On Improving Mechanical Properties Of Physically Crosslinked Hydrogel Scaffolds

Hydrogel scaffolds have got much concern in materials science and biomedical engineering,partly because of its porous network structure similar to that of extracellular matrix(ECM),and partly because it can carry functionalized small molecules such as drugs,enzymes,peptides,and growth factors during the gelation process.However,conventional hydrogels or some specific functionalized hydrogels cannot have good application prospects because of poor mechanical properties or inhibited cellular behaviours.Fiber-reinforced hydrogel as a composite material,using fibers as the reinforcements to improve specific properties,this study made the combination of biodegradable poly(lactic acid)-hydroxyacetic acid copolymer(PLGA)/polycaprolactone(PCL)/gelatin(GEL)electrospun nanofibers with sodium alginate(ALG)/chitosan(CS)polyelectrolyte complex hydrogel and polyvinyl alcohol(PVA)freezing-thawing physically cross-linked hydrogel to prepare two nanofiber-reinforced hydrogel scaffolds,respectively.The physicochemical and biological properties of the hydrogel scaffolds were investigated.First,PLGA were combined with PCL using electrospinning,and GEL was added to improve the biocompatibility and functionalization.With the increase of PLGA,the fiber diameter gradually decreased to a minimum of600 μm.Tensile tests showed that the increase of PLGA could improve the modulus,while the addition of PCL could improve the elongation at break.With the increase of PLGA,the rate of fiber degradation was accelerated.In the late degradation stage,the higher the PLGA content,the fiber morphology is about blurred.Then,the reinforcement of PLGA/PCL/GEL nanofibers on ALG/CS polyelectrolyte complex hydrogels was explored.CS/ALG/PPG/TA hydrogel scaffolds(CATPPG)were prepared by using dispersed short nanofibers and tannic acid(TA)hydrogen bonds crosslinking.The microscopic morphology showed that the nanofibers were wrapped in the lamellar network or linked between adjacent polyelectrolyte networks,and the formation of hydrogen bonds made fibers structurally stable with the polyelectrolyte network.CAT0.3 with 0.3 g PPG nanofibers added possessed the highest water absorption and swelling rate(～3800%),which was related to the maximum porosity(96.0%)and pore size(40.82 μm)of CATPPG.Meanwhile,the mechanical properties of the nanofibers added group were improved compared with the control CA group,and the compressive modulus of CAT0.9 reached665 KPa and the maximum compressive stress reached 342 KPa,which increased the maximum compressive stress by 53%.During the compression cycles,the degree of plastic deformation and stress loss of the nanofibers added group were lower,indicating that nanofiber as the reinforcing phase enhanced the strength of hydrogel network.By subcutaneous implantation in rats,an acute inflammatory phase was found at 1 week,while the inflammatory response basically disappeared after 4 weeks.Meanwhile,to improve the ability of poor cell adhesion of PVA hydrogel,PVA/COL/PPG hydrogel scaffold(PCPPG)was prepared by freezing-thawing cycles by mixing dispersed PLGA/PCL/GEL short nanofibers with PVA and collagen(COL).The nanofibers were distributed in the hydrogel network,resulting in a denser network structure.Hydrogen bonds and new amide bonds were generated because of the cross-linking process,and the thermal stability of the hydrogel was thus improved.The porosity and average pore size of PCPPG were smaller than those of CATPPG,while the pore area is larger,which also proved its denser hydrogel structure.The best water absorption and swelling performance was obtained for PC0.6,while the water content of the four groups was similar.With the increase of PPG content,the compression strength was improved,and the average compression strength of PC0.9 reached 0.6 MPa.Meanwhile,nanofibers incorporation resulted in a reduction of the maximum compressive stress loss during compressive cycles,from 39.88% to 23.61%,indicating that nanofibers can enhance the ability to maintain mechanical stability.Cell activity assay showed that more cells adhered to the scaffold in PC0.6 and PC0.9,which improved the poor cell adhesion.The results of 1 and 4 weeks of subcutaneous implantation in rats showed essentially no inflammatory response.