| OBJECTIVESThe prevention and treatment of painful traumatic neuromas have long been animportant challenge for plastic and reconstructive surgeons. Although a variety oftreatment modalities have been introduced in literature, only several approaches have beenwidely accepted and carried out. Nerve capping technique, as one of the few methods thathave been thought to be effective in this field, has been limited in application due to theavailability of nerve conduits in clinical practice. In this research, we investigated thepreventive and therapeutic effect of the biodegradable aligned nanofiber nerve conduits onthe formation of painful traumatic neuromas and further explored its associatedmechanism in this situation, attempting to provide theoretical support and new treatmentstrategies for the management of this intractable neuropathic pain.METHODSThe aligned and non-aligned nanofibrous scaffolds were first fabricated using coaxialelectrospinning technique according to our previous studies. The morphology and growthstatus of Schwann cells on the aligned and nonaligned nanofibrous scaffolds wereobserved and the impacts of the two types of nanofiber scaffolds on the maturity and expression levels of cytokines of SCs were investigated; next, the nerve conduits using thefabricated nanofiber scaffolds were made and the sciatic nerves of Sprague Dawley ratswere used as the animal model of traumatic neuromas. The results of autotomy behavior,weight increasing ratio of neuromas and morphologic and histological changes in theneuromas were compared among groups to analyze the influences of different types ofnanofiber conduits on the formation and pain status of neuromas; finally, the investigationof the possible mechanism of nerve capping technique using aligned nanofiber conduits inprevention of posttraumatic painful neuromas was carried out by analysis of the effects ofthe aligned nanofiber conduits on the morphologic, biomolecular and pain status changes.RESULTSThe SCs in the aligned nanofibrous scaffolds elongated following the orientation ofthe nanofibers, in contrast, the proliferation of SCs in the random scaffolds was observedin a multidirectional manner, indicating the alignment of the nanofibers could control cellorientation. The maturity of SCs cultured in the aligned scaffold was much better than thatcultured in the random scaffold; meanwhile, the expression of cytokines, such as TGF-β1and NGF, which are closely associated with tissue proliferation, was significantlydown-regulated in the SCs cultured in the aligned nanofiber scaffold compared with thatin the random nanofiber scaffold (p<0.001). In the animal study, obvious bulb-likeneuromas were seen in the no-capping control group while no such presentation wasobserved in the capping groups; the average autotomy score, weight increasing ratio ofneuromas and the expression level of pain-related protein were all significantly higher inthe no-capping group than those of the non-aligned nanofiber capping group, and theseparameters were the lowest in the aligned nanofiber capping group among the three groups(all p <0.01). Further study demonstrated that a more mature regenerated nerve fibers andSCs and a lower expression level of related cytokines were observed in the alignedcapping group in comparison with the no-capping group. In addition, the gene expression level of RhoAin the corresponding dorsal root ganglions was significantly higher than thatof the no-capping group, while the expression level of alpha smooth muscle actin (-SMA)was significantly lower than that of the no-capping group (both p<0.001).CONCLUSIONSIn this study, capping by the aligned nanofiber conduit could alter the regenerationstate of transected nerves from a random manner to a linear one, promote the maturity ofregenerated nerve fibers, possibly initiating a regeneration brake signal to inhibit theneuroma growth and eventually contributing to the prevention of neuroma formation; thefacts that capping by the aligned nanofiber conduit greatly suppressed the expression ofself contractile-SMA, which may entrap the nerve fibers within the neuromas and NGF,which may act as a potential pain mediator, may be the possible mechanism of the nervecapping technique using the aligned nanofiber conduit in preventing the onset ofneuropathic pain. These findings indicate that the aligned nanofiber conduit is a promisingbiomaterial for the capping technique and new treatment strategy using aligned nanofiberconduits may be developed for the management of painful amputated neuromas. |
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