Long-term in vivo biomechanical properties and biocompatibility of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) nerve conduits

Artificial grafts are promising alternatives to nerve grafts for peripheral nerve repair because they obviate the complications and disadvantages associated with autografting such as donor site morbidity and limited tissue availability. We have synthesized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their efficacy in vivo. Specifically, we studied the short- and long-term stability and biocompatibility of 12 mm long tubes for the repair of surgically created 10 mm nerve gaps in rat sciatic nerves. Prior to implantation, tubes were analyzed in vitro using a micro-mechanical tester to measure displacement achieved with load applied. These results served as a calibration curve, y = 6.8105 x -0.0073 (R2 = 0.9750, n = 28), for in vivo morphometric tube compression measurements. In vivo, most of the PHEMA-MMA conduits maintained their structural integrity up to 8 weeks, but 29% (4/14) of them collapsed by 16 weeks. Interestingly, the tube wall area of collapsed 16-week tubes was significantly lower than those of patent tubes. Tubes were largely biocompatible; however, a small subset of 16-week tubes displayed signs of chronic inflammation characterized by "finger-like" tissue extensions invading the inner tube aspect, inflammatory cells (some of which were ED1+macrophages) and giant cells. Tubes also demonstrated signs of calcification, which increased from 8 to 16 weeks. To overcome these issues, future nerve conduits will be re-designed to be more robust and biocompatible.