| Traumatic peripheral nerve injury is a commonly encountered disease in clinic.The spontaneous regeneration is limited to some extent.FDA approved nerve guidance conduits(NGCs)are confined to lesions less-than 30 mm and seldom have achieved full functional recovery after nerve injury.When bridging repair of a long distance nerve defect,the hollow NGC may induce a random dispersion of regenerating axon and further result in inaccurate target re-innervation.Biomimetic NGCs with intraluminal fillers have been developed to resemble the endoneurial structure of peripheral nerve,further create a desirable microenvironment and act as contact topographical cues to enhance axonal regeneration.Bacterial cellulose(BC)is widely used in biomedical field due to its high specific surface area,high water holding capacity and good bio compatibility.There are few reports on peripheral nerve scaffold constructed use BC.In this study,a biomimetic nerve guidance conduit was prepared and charactrized for its physicochemical properties and biocompatibility.Furthermore,the novel NGC was applied for repairing a 10-mm-long gap rat sciatic nerve.The experimental conditions of electrospinning polyglycolic acid(PLGA)nanofiber membrane were optimized by exploration of the optimal parameter.15%(w/v)PLGA solution was prepared for electrospinning.The electrospinning was implemented with a positive voltage of 10 k V at a flow speed of 0.4 ml/h.A constant distance was optimized at 15 cm between the collecting aluminum foil and the steel needle.In these conditions,uniform and continuous nanofiber films can be obtained,with diameter of 283±73 nm and the distribution of diameter of the fiber is between100-500 nm.The tensile strength of the nanofiber membrane with a thickness of 0.2mm reached to 3.1 MPa.This PLGA nanofiber can provide suitable porous structure for nutrients and gas exchange as well as adequate mechanical properties for nerve regeneration.Biodegradable BC was developed by periodate oxidation,and further evaluated its biocompatibility in vitro.The oxidation process gradually increased diameter of each fiber along with denser 3D network nano-structures and both of_fand?_f for oxidized bacterial cellulose(OBC)scaffolds reduced gradually.The biodegradability of OBC scaffolds with oxidation degree(O.D.)value lower than 9.3%is nearly 15times than that of corresponding incubated BC scaffold.OBC-COL composite scaffold was prepared by using schiff base reaction,OBC-COL scaffolds with different cross-linking degrees can be obtained by adjusting the mass ratio of OBC and COL.The OBC-COL composite scaffold preserved a three-dimensional interconnected reticular porous structure,with high length-diameter ratio,and a porosity of over 70%.The pore diameter of 10-100?m were accounting for 70%.Thermostability of OBC-COL scaffold was improved obviously after crosslinked OBC and COL through schiff base reaction.The OBC-COL2 exhibited better cell biocompatibility.The novel NGC was prepared containing intraluminal sponge fillers and used for reconstruction of a rat sciatic nerve with 10 mm gap.The results showed that intralumina sponge filled nerve guidance conduit(ISF-NGC)could effectively promote nerve regeneration.The maturity of myelin sheath in ISF-NGC was significantly better than that of hollow nerve guidance conduit(H-NGC),and there was no significant difference with autograft.The SFI value of ISF-NGC group was close to that of autograft group.It is likely that the H-NGC only provides a protected tunnel for nerve fiber regrowth and axonal extension,while ISF-NGC offers an extracellular matrix(ECM)-mimetic architecture as autograft to provide contact guidance for nerve regeneration and extension,futher facilitate the nerve re-innervation process.The results suggest that the ISF-NGC is more conducive to limit muscle atrophy than H-NGC during nerve regeneration.In conclusion,the ISF-NGC can effectively promote nerve regeneration and functional recovery,with a good clinical value. |
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