The development of a compression and kink resistant nerve guide for the treatment of painful neuromas

摘要

Introduction: Peripheral nerve when severed from trauma or disease can regenerate at the proximal end, however, unguided nerve growth tends to form an unorganized mass or neuroma that becomes painful and can reoccur after a surgical resection. Application of a flexible collagen nerve guide, NeuroFlex™ (Collagen Matrix Inc.) for capping or redirection of nerve endings following neuroma incision has been shown clinically in human and cleared by the FDA as a treatment for painful neuromas in the foot. Based on the clinical study, the success of NeuroFlex™ was due to its kink resistance that allowed redirection of the nerve ending from the sole of the foot to the compression-free dorsum region. However, in areas that are sensitive to compression and nerve redirection is not practical, the treatment outcome was suboptimal. This study aimed to develop an improved nerve guide that is resorbable and possesses improved compression and kink resistance, which are critical to successful treatment of painful neuromas at all anatomical sites. Materials and Methods: Design: Compression and kink resistant collagen nerve guide (CKRNG) was engineered by circumferentially winding resorbable synthetic filament of poly (L-lactide-ε-caprolactone) (PLC, 75:25 w/w polylactide to polycaprolactone)) between two layers of type Ⅱ collagen fibers from bovine Achilles tendon. CKRNGs were cross-linked, rinsed, freeze-dried, packaged and sterilized. In vitro characterization: CKRNGs were hydrated and compressed transversely at 1.3 cm/min until walls came into contact to yield maximum force, termed compression resistance. Hydrated CKRNGs were allowed to bend along a reference angle until a kink was formed, and the angle just prior to kink formation was recorded. In vivo resorotion in rabbits: CKRNGs and NeuroFlex™ were implanted into the subcutaneous tissue of New Zealand White rabbits using a standard surgical method. At time-points of 2,6,13, and 26 weeks, implant sites were collected for histological processing and analysis. PLC was extracted from some implanted CKRNGs to evaluate the changes in tensile strength and molecular weight for assessment of the resorption rate of the PLC. Results and Discussions: CKRNG showed ＞3 folds higher in compression resistance, and significantly improved kink resistance when compared to those of NeuroFlex™. The resorption profile of CKRNG and NeuroFlex™ were similar, with the total resorption time of approximately 50 weeks, as extrapolated from the curve-fitted profile. PLC filament within the CKRNG was found to have a total resorption time of approximately 40 weeks. Conclusion: CKRNG is a resorbable nerve guide that possesses greatly improved compression and kink resistance over NeuroFlex™. It shows high potential as a more effective treatment for painful neuromas in compression-sensitive areas, and further development will be continued for performance evaluation in human in the near future.