Study of smart conduits made of shape-memory polymers for peripheral nerve regeneration

Abstract

Shape-memory polymers (SMPs) are defined by their capacity to recover an initial shape from temporary deformations upon external stimulation. They have gained increasing attention over the recent decade in biomedical applications. Reported medical devices based on SMPs range from general surgical to intravascular applications and filling materials to drug delivery systems. However, there have been few reports on applications of SMPs to nerve regeneration. Yet, peripheral nerve repair and regeneration have been a unique clinical challenge for surgeons. Herein, we propose a novel kind of smart nerve conduit fabricated from SMPs that can achieve peripheral nerve regeneration by automatic lengthening. The design concept, preparation process, structure characterization, function evaluation, mechanism analysis for the SMPs and SNCs were presented in this thesis. Briefly, a series of macromers with different (rac-lactide) to glycolide weight ratios were synthesized and the characteristics of the synthesized networks were studied. Cyclic thermo-mechanical measurements indicated the robustness of molecular structure for shape memory function. Body-water responsive shape-memory behavior was evaluated by angle recovery measurements. The shape recovery time of the polymer could be adjusted by the selection of comonomer ratio and then the overall gradual-recovery function of a device could be realized by suitable combination of different copolymers. Thus a tri-segment smart nerve conduit was fabricated from this polymer system by electrospinning, shown to gradually recover in an in vitro experiment under stimulated physiological conditions, that is, body-liuid environmemnt (36°C water). In vitro culture and qualitative immunocytochemistry of Schwann cells assessed the biocompatibility of poly(rac-lactide-co-glycolide) networks. In vivo experiments in rabbit animal model were conducted to ensure the SNC has the required mechanical characteristics to perform adequately under practical conditions.