Nerve conduits and growth factor delivery in peripheral nerve repair

Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Transected peripheral nerves can be bridged by direct surgical coaptation of the two nerve stumps or by interposing autografts or biological (veins) or synthetic nerve conduits (NC). NC are tubular structures that guide the regenerating axons to the distal nerve stump. Early synthetic NC have primarily been made of silicone because of the relative flexibility and biocompatibility of this material and because medical-grade silicone tubes were readily available in various dimensions. Nowadays, NC are preferably made of biodegradable materials such as collagen, aliphatic polyesters, or polyurethanes. Although NC assist in guiding regenerating nerves, satisfactory functional restoration of severed nerves may further require exogenous growth factors. Therefore, authors have proposed NC with integrated delivery systems for growth factors or growth factor-producing cells. This article reviews the most important designs of NC with integrated delivery systems for localized release of growth factors. The various systems discussed comprise NC with growth factors being released from various types of matrices, from transplanted cells (Schwann cells or mesenchymal stem cells), or through genetic modification of cells naturally present at the site of injured tissue. Acellular delivery systems for growth factors include the NC wall itself, biodegradable microspheres seeded onto the internal surface of the NC wall, or matrices that are filled into the lumen of the NC and immobilize the growth factors through physical-chemical interactions or specific ligand-receptor interactions. A very promising and elegant system appears to be longitudinally aligned fibers inserted in the lumen of a NC that deliver the growth factors and provide additional guidance for Schwann cells and axons. This review also attempts to appreciate the most promising approaches and emphasize the importance of growth factor delivery kinetics.