Application of a Porcine Small Intestine Submucosa Nerve Cap for Prevention of Neuromas and Associated Pain

Abstract

Painful neuroma formation is a common and debilitating sequela of traumatic or oncologic nerve amputations. Studies suggest that isolating transected nerve stumps within protective caps during amputation surgery or revision procedures may assist in preventing symptomatic nerve-end neuroma formation. This study evaluated the local effects of two porcine small intestine submucosa (pSIS) nerve caps of differing configurations on a terminal nerve end in an animal model. The tibial nerves of 57 Sprague Dawley rats were transected and transposed to the lateral hind leg. The nerves were treated with one of three SIS materials, including (i) a nerve cap with spiraling chambering, termed spiral nerve cap (SNC), (ii) a nerve cap with bifurcated chambers termed chambered nerve cap (CNC), or (iii) an open tube. The surgical control consisted of nerve stumps that were not treated. Overall tissue response, axonal swirling, optical density of axons, and behavioral pain response were quantified at 8 and 12 weeks postoperatively. There were no notable differences between the performance of the SNC and CNC groups. The pSIS nerve caps mitigated aberrant axonal regeneration and decreased neuroma formation and associated pain response. These findings suggest that nerve caps with internal chambers for axonal outgrowth may improve axonal alignment, therefore reducing the likelihood of symptomatic neuroma formation.

Implantation of a nerve protector embedded with human GMSC-derived Schwann-like cells accelerates regeneration of crush-injured rat sciatic nerves

“…S1a). This is in consistent with previous studies, whereby SIS nerve guidance conduits (NGCs) stably maintained their shape without collapsing for up to 8 weeks [ 46 ] and showed minimal-to-mild resorption by up to 12 weeks following implantation in vivo [ 47 ]. Immunofluorescence (IF) studies indicated that those transplanted GMSCs integrated into the wall matrix of NPs and localized in the peripheral areas outside of the injured nerves as recognized by the positive expression of human nuclei, whereas only about 5% of them were positively stained for the active form of caspase-3 (Additional file 1 : Fig.…”

Development of an acellular nerve cap xenograft for neuroma prevention

“…21,22 Commercially available nerve capping devices made of synthetic or biological degradable materials are intended to provide protection from the tissue injury inflammatory environment. 8,9 While these devices can provide a macrostructural template to contain axonal regeneration, they can also create nerve "compartment syndrome" as they can become a "barrier/trap" for growing/sprouting axons. Furthermore, the degradation products of the synthetic material used for one of these technologies (PLLA-PCA) has been associated with a fibrotic inflammatory response, which can further increase the risk of neuroma formation.…”

“…These devices can be made of synthetic or biologic materials and appear to attenuate painful neuroma formation, potentially by isolating free sensitized axons. While the cap devices have shown promising results in preclinical studies, 8,9 they have yet to be widely adopted, as the limited clinical evidence available suggests that nerve capping remains inferior to existing surgical approaches 7 . Recent studies have demonstrated that application of an acellular allograft provides a template for termination of the axonal growth potential within the length of the device 10 ; while this approach has shown promise, the length (i.e., 5 cm) of allograft required to exhaust the regenerative potential of the injured nerve creates the need for a more extensive surgical site 11 …”

A Photosealed Cap Prevents Disorganized Axonal Regeneration and Neuroma following Nerve Transection in Rats

“…5 When no viable distal nerve target is available (eg, amputation), the surgical approach to prevent neuroma formation often focuses on inhibiting axonal regrowth from the injured proximal nerve stump. Mechanisms studied to prevent disorganized axonal regrowth include implantation of the proximal nerve stump into adjacent tissue, [6][7][8][9] nerve coaptation, [10][11][12][13] nerve conduits, [14][15][16][17][18] and nerve capping, [19][20][21][22][23][24] with mixed results.…”