Optimizing the design of synthetic peripheral nerve conduits

Abstract

Event Abstract Back to Event Optimizing the design of synthetic peripheral nerve conduits Divya Bhatnagar1, Jared Bushman1, Basak A. Clements1, Sanjeeva Murthy1 and Joachim Kohn1 1 Rutgers University, New Jersey Center for Biomaterials, United States Introduction: Many fundamental design parameters for nerve conduits are still poorly understood, including key questions such as: (i) does the composition of the material used to construct the nerve conduit directly effect the rate of nerve regeneration; (ii) how can the kink resistance of conduits be improved to allow their use across articulating joints, (iii) what is the optimum level of conduit wall porosity for oxygen and nutrient exchange. We have attempted to address these questions. Materials and Methods: Braided conduits (Fig. 1) were fabricated from tyrosine-derived polycarbonate. Kink resistance and mechanical properties were optimized by changes in the braiding pattern. Braided conduits had walls with pores (~100 µm pore diameter). The conduits were coated with fibrin glue or hyaluronic acid to modify the overall porosity. The relationship between wall porosity and nerve regeneration was studied using the 1 cm rat sciatic nerve injury model. Nerve regeneration was evaluated in terms of axonal density, G-ratio (axonal to fiber diameter), myelinated area, and functional outcome measures such as recovery of muscle mass, electrophysiology (CMAPs), and recovery of mobility. Results: Since the regenerating nerve cable rarely contacts the conduit wall directly (Fig. 2), it has long been debated to which extent the conduit material affects nerve regeneration. To address this question, we directly compared identically sized nerve conduits made of either polyethylene (a poor substrate for the adsorption of endogenous proteins) or a tyrosine-derived polycarbonate (an excellent substrate for the adsorption of endogenous proteins). We observed significantly better nerve regeneration for tyrosine-derived polycarbonate conduits, consistent with increased adsorption of laminin, fibronectin, and collagen 1 on their luminal surface. This, in turn, influences the biological microenvironment that is created within the conduit. Next, we addressed the need to create kink-resistant conduits that can be used across articulating joints. We found that braiding provides conduits with superior mechanical properties and excellent kink resistance and offers significant advantages, including the ability to optimize mechanical properties by changing the yarn diameter and braiding pattern, as well as changing the porosity of the conduit wall. Braiding has not yet been extensively explored. Control of wall porosity (by different coatings) proved to be a critical design parameter[1]: Substantial porosity led to significant ingrowth of fibrous tissue resulting in poor nerve regeneration. We observed a porosity-controlled competition between the growing nerve cable and infiltrating scar tissue. The outcome of this competition has a profound effect on the functional outcome of nerve regeneration (Fig.3). Conclusions: (i) Materials that support the adsorption of endogenous proteins can have a neurotrophic effect without being in direct contact with the regenerating nerve cable. Choosing materials that have a high tendency to adsorb endogenous laminin, fibronectin and collagen may therefore be an important selection criterion for the design of nerve conduits. (ii) Braiding provides excellent mechanical properties and kink-resistance and has so far been overlooked as a method for conduit fabrication. (iii) Control of conduit wall porosity is critical to balance the need for nutrient and O2 exchange while limiting the infiltration of scar tissue. This work was financially supported by an NIH Bioengineering Research Partnership grant R01NS078385.