Effects Of Polylactic-co-glycolic Acid Nerve Guide Combined With Topical Application Of Tacrolimus And Mycophenolate Mofetil On The Repair And Regeneration Of Small Gap Defects In Sciatic Nerve In Rats

Both mycophenolate mofetil(RS-61443)and tacrolimus(FK506)are commonly used clinical immunosuppressants,and they were mainly used in internal organ transplantation or limb transplantation in the early stage,so as to inhibit the transplanted internal organs or Immunogens brought by limbs.After a lot of research,it has been confirmed that FK506 is immunosuppressive and has the function of promoting the regeneration of damaged peripheral nerves.However,whether RS-61443,which is also an immunosuppressant,has the same function is still the field of our research.Although relevant studies have proved that RS-61443 can promote the recovery of neurosensory ability,further research and the application of combined nerve catheters are still an area of exploration.As a representative of bionic catheter,PLGA nerve guide is the “bridge”;between the two stumped nerves in our study.In our study,RS-61443 can achieve the same or weaker peripheral nerve repair function as FK506,and the recovery effect has been greatly improved when the two are used together.The “gold standard”autograft was equal or slightly lower.The delivery of drugs and the guidance of biological catheters provide guarantees for nerve repair and provide a new field for the future field of nerve regeneration.Objectives:To study the effects of immunosuppressants FK506,RS-61443 and their combination in the biomimetic material PLGA nerve conduit to promote the repair and regeneration of peripheral nerves in transected small gaps.Methods:Thirty male Sprague Dawley(SD)rats were divided into 5 groups,6 rats in each group,including empty catheter group,FK506 group,RS-61443 group,FK506+RS-61443 group,and autologous transplantation group.The concentrations of FK506 and RS-61443 were adjusted to 0.25 ㎎/ml and 20 ㎎/ml for use.Before the experiment,the PLGA nerve guide was soaked in the two drugs for 24 h,and then 100 μ l of the two immunosuppressants were filled in the PLGA guide tube respectively,and give the medicine once a week.Empty in the hollow catheter without filling any reagents.At 12 weeks after operation,the acupuncture test,hot plate test,gait test,weight loss ratio of gastrocnemius muscle,Masson staining,immunohistochemistry and western blotting experiments were measured in SD rats.Results : 1)Filling FK506 and RS-61443 in PLGA biocatheter can effectively promote nerve regeneration,and the effect of RS-61443 is slightly lower than that of FK506 group.2)The double-drug FK506+RS-61443 group seems to be able to achieve similar or slightly lower effects than the autograft group in terms of histomorphology and microscopic expression,effectively promoting the repair of rat sciatic nerve defects of about 10 mm,but the leg function recovery Slightly lower than the autograft group.The findings of these studies will benefit future development of superior strategies for repairing peripheral nerve transection defects.Conclusions : Conclusion: Whether it is the expression of Schwann cells,neurofibromin and myelin protein,or the recovery of leg movement function,RS-61443 single-drug catheter group is a very potential immunosuppressant.In the case of combined application with FK506,the overall effect is slightly lower than that of the autograft group,but stronger than that of the two singledrug groups.This is undoubtedly a new discovery in the field of NGC repairing nerve defects.