The Novel Use of a Nanofiber Hydrogel Composite for Perineural Adhesion Prevention in a Rodent Model

Abstract

INTRODUCTION: Perineural adhesions can form after any surgical intervention involving peripheral nerves. Adhesion formation may then lead to nerve entrapment and compressive neuropathy, which can result in a wide variety of symptoms ranging from sensory deficits to motor weakness. Previously, we created a novel poly(ε -caprolactone) (PCL) nanofiber/ hyaluronic acid hydrogel composite that was shown to mimic the microarchitecture and mechanical properties of soft tissue extracellular matrix.1 We hypothesize that the use of this novel nanofiber hydrogel composite (NHC) will reduce perineural adhesion formation in a rodent hindlimb model. METHODS: This study was performed with Institutional Animal Care and Use Committee approval. Male Lewis rats underwent bilateral circumferential mechanical irritation of the sciatic nerve to induce adhesion formation with subsequent primary closure. Animals then underwent a secondary neurolysis 8 weeks post-operatively. At the time of neurolysis, the experimental group (n=6) were treated with circumferentially application of NHC around the sciatic nerve before closure and the control group were closed without treatment (n=6). Both groups were sacrificed 8 weeks after their secondary surgery. At the time of euthanasia, all rodents underwent unilateral biomechanical force testing to assess the breaking point of the perineural adhesions surrounding the sciatic nerve (measured in Newtons). In the contralateral limb, the sciatic nerve, surrounding muscle, and NHC in experimental animals was harvested to assess perineural collagen deposition using hematoxylin and eosin (H&E) and Masson’s Trichrome staining. RESULTS: Significant perineural adhesions were visually apparent after sciatic nerve irritation in the control group. In the experimental group, the sciatic nerve was grossly encapsulated by the NHC which closely resembled subcutaneous fat with visible neovascularization. Biomechanical testing demonstrated the average force required to remove the nerve from the wound bed in the experimental group was 2.02±0.43 N. In the control group, the sciatic nerve could not be removed from the wound bed and the average force prior to failure was 2.77±0.18 N. Collagen deposition, a measure of scar formation around the sciatic nerve, was assessed via H&E and MT staining. Minimal collagen deposition was seen in the experimental group compared to control, indicating a decrease in scar formation in the animals treated with perineural application of the NHC. CONCLUSION: We found that the use of a novel PCL nanofiber/hyaluronic acid hydrogel composite resulted in a decrease in perineural adhesion and scar formation in a rat model. 1. Li X, Cho B, Martin R, Seu M, Zhang C, Zhou Z, Choi JS, Jiang X, Chen L, Walia G, Yan J, Callanan M, Liu H, Colbert K, Morrissette-McAlmon J, Grayson W, Reddy S, Sacks JM, Mao HQ. Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction. Sci Transl Med. 2019 May 1;11(490):eaau6210. doi: 10.1126/scitranslmed.aau6210. PMID: 31043572.