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The Novel Use of A Nanofiber Hydrogel Composite for Primary and Recurrent Perineural Adhesion Prevention in a Rodent Hindlimb Mode
Visakha Suresh, MD1; Thomas G.W. Harris, MBChB2; Chenhu Qiu, MS3; Jarvis Kong, BS3; Sashank K Reddy, MD4; Hai-Quan Mao, PhD3; Sami H Tuffaha, MD5
1Johns Hopkins University School of Medicine, Baltimore, MD; 2Johns Hopkins School of Medicine, Baltimore, MD; 3Johns Hopkins University, Baltimore, MD; 4Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD; 5Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD

Perineural scarring and adhesions following surgical nerve exposure can result in symptomatic entrapment and compressive neuropathy. Previously, we created a novel poly(?-caprolactone) nanofiber/hyaluronic acid hydrogel composite (NHC) that mimics the microarchitecture of extracellular matrix to down regulate the inflammatory response and facilitate incorporation. We hypothesize that this NHC will reduce post-surgical perineural adhesions and scar formation in a rodent sciatic neurolysis model. Male Lewis rats underwent bilateral circumferential sciatic nerve neurolysis and mechanical irritation of the surrounding wound bed to induce scar formation. Primary neurolysis cohorts were either treated with perineural NHC or left untreated (N=6 per group) during initial exposure and underwent endpoint analyses 8 weeks later (N=6 per group). Secondary neurolysis cohorts were all left untreated during initial surgical exposure. They subsequently underwent surgical re-exposure 8 weeks later with perineural NHC application or no treatment, followed by endpoint analyses 8 weeks following secondary re-exposure (N=6 per group). Endpoint analyses included biomechanical testing to assess the breaking point of the adhesions surrounding the sciatic nerve (Newtons). In the contralateral limb, the sciatic nerve were harvested en block with surrounding tissues to histologically assess perineural collagen deposition. Expression of pro- and anti-inflammatory cytokines was evaluated with PCR and ELISA. In NHC-treated animals, the average force required to dislodge the sciatic nerve from its wound bed was 0.69 0.11 and 2.020.43 Newtons, in primary and secondary neurolysis cohorts, respectively. In untreated control animals, the nerve could not be removed from surrounding wound bed; the average maximum force prior to nerve rupture was 2.98 0.57 and 2.770.18 Newtons in primary and secondary neurolysis cohorts, respectively. In the primary neurolysis cohort, average percentage of perineural collagen deposition was 21.4 4.4 and 4.6 1.4% in control and experimental groups, respectively (p < 0.0001). In the secondary neurolysis cohort, average percentage of perineural collagen deposition was 47.8 5.8 and 16.7 3.7% in control and experimental groups, respectively (p < 0.0001). In all treated animals, there was significant up-regulation of anti-inflammatory cytokines (TGF-?, IL-10); whereas untreated animals demonstrated significant up-regulation of pro-inflammatory cytokines (TNF? and IL-1b). Treatment with NHC at the time of primary or secondary surgical exposure and neurolysis reduces perineural adhesion formation, decreases collagen deposition, and increases upregulation of anti-inflammatory gene expression.


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