Guided regeneration with resorbable conduits in experimental peripheral nerve injuries

Abstract

Guided tissue regeneration is a new approach in the reconstructive surgery of peripheral nerves. Artificial conduits can be constructed from biodegradable polymers. Lactic/caproic acid copolymers and polyphospazenes are biocompatible materials with a slow resorption rate. Conduits made from either poly-[l-lactide-co-6-caprolatone] or poly-[bis-(ethylalanate)-phosphazene] were assessed for use as guides for nerve regeneration in experimental animals. Under general anesthesia and by using a microsurgery technique both sciatic nerves were exposed in 2 groups of 9 Wistar rats. On the right side, a 10 mm segment of the nerve was removed, and the defect was then repaired using a conduit. On the left side, the same defect was bridged using as an autograft the nerve segment, which had been removed from the right sciatic nerve. Histological and electron microscopy investigations were performed after 30, 90 and 180 days and showed the gradual degradation of both types of conduits without any evidence of local toxicity. The regeneration of the nerve fibers in the lumen was not significantly different from that shown by the autologous grafts. Likewise, no differences were found at 180 days in the functional recovery of the nerve (evoked muscle action potential). Both conduits were found to be effective for guided nerve regeneration. Poly-[l-lactide-co-6-caprolactone] tubes were easier to insert, while polyphosphazene conduits allowed the use of neurite-promoting factors.Résumé La régénération tissulaire guidée est une nouvelle perspective dans la reconstruction des nerfs péri-phériques. Des conduits artificiels peuvent être obtenus avec des polymères biodégradables. Nous avons évalué dans un modèle expérimental deux types de polymères le poly-[1-lactide-co-6-caprolactone] et le poly-[bis-(etilalanate)-phosphazene]. Cette expérimentation a été, conduite sous anesthésie générale au niveau du nerf sciatique de 9 rats Wistar, un segment de 10 mm de nerf a été réséqué et du côté droit la reconstruction a été faite en utilisant une polymère du côté gauche, la réparation a été faite avec une autogreffe avec le segment réséqué du cô-té opposé. Une étude histologique et par microscopie électronique a été faite à 30, 90 et 180 jours. Il n'y a pas eu de toxicité locale des conduits en polymère. La régé-nération des fibres nerveuses dans les deux types de conduits ne fut pas différente de celle observée avec les autogreffes. Les deux types de conduits peuvent être considérés comme efficaces pour guider la régénération nerveuse. Le tube en polycaprolactone est plus maniable alors que celui en polyphosphazene peut contenir des facteurs favorisant la croissance axonale.

Impact of scaffold micro and macro architecture on Schwann cell proliferation under dynamic conditions in a rotating wall vessel bioreactor

“…Despite the early promise of tissue engineering, researchers have faced challenges in regenerating peripheral nerve tissues over large gaps (exceeding 4 mm) [1, 2, 4]. Current tissue engineering approaches investigate the use of bioactive or bioresorbable matrices, which rely on the appropriate cellular response In Vivo , with the development of biological and physical functionality post implantation [5, 6]. A limitation of this approach is the inconsistency of the host response in terms of resorption, recellularisation and regeneration, which can result in development of inappropriate regeneration parameters, and hence failure of the implanted graft to perform its role of regeneration [7,8].…”

Tissue‐Engineered Peripheral Nerve

“…As mentioned, polyglycolic acid tube guides have been shown to support regeneration when filled with collagen-based scaffolds. Hollow guides made from polycaprolactone (22) and copolymers of polylactic acid and polycaprolactone (23) have also demonstrated promise of full morphometric and functional recovery at levels similar to autograft controls in 10-mm rat sciatic nerve defects. Polyphosphazene is an inorganic polymer with a backbone containing nitrogen and phosphorus.…”

“…One subclass, poly-organo-phosphazenes, hydrolytically degrade into phosphate and ammonium derivatives. Nicoli-Aldini et al investigated poly-(bis-(ethylalanate)-phosphazene) as a model degradable polymer characterized for its ability to controllably release drugs embedded within its matrix (23). These hollow guides were also found to be comparable with the autograft in guiding functional regeneration.…”

Ultrastructural analysis of guided nerve regeneration using progesterone‐ and pregnenolone‐loaded chitosan prostheses

“…Tubulation techniques produce minimal surgical trauma, guide nerve growth, protected intrinsic growth factor contained in situ , and allow the application of neurotrophic substances or cells into the chamber lumen, with strong influence on nerve fiber regeneration 6, 9–12. This ability of a nerve to regenerate through artificial conduits is considered to be the first example of guided tissue regeneration (GTR) and is a new concept in surgical practice (dental surgery, surgery, and peripheral nerve) 13. Furthermore, this technique has shown regenerative responses similar to those obtained with autografts in some animals species and humans 1, 2, 7, 8.…”

“…For this reason, the use of biodegradable materials, such as poly‐caprolactone (PCL), polyglycolide (PGA), polylactides (PLLA, PDLA), polyphosphazenes, chitosan, and others, have brought new possibilities for nerve repair, rendering better results than silicone chambers when bridging nerve gap defects 10 mm or longer in animal species larger than rodents 4, 5, 9, 11–13. Those materials have been used as nerve guide (prosthesis) and drug delivery devices for in situ application of pharmacological agents or cells that may enhance successful the regeneration of the nerve fibers and the functional recovery of injury nerves 4, 9–15. Furthermore, biodegradable prostheses offer several advantages such as to exert a bioactive interaction with their receptor tissue,14 to suffer a gradual biodegradation, permitting them to act as a temporal physical substrate to guide nerve growth, and to induce biological effects acting as drug or cell delivery devices 9, 10, 12, 14, 15…”