(570b) 3D-Printed PLLA-Peg-PLLA Nerve Guidance Channels for Peripheral Nerve Repair

The peripheral nervous system (PNS) is vulnerable and can be easily damaged by injuries or trauma. Surgical treatment is the only effective and currently available method, with the gold standard for defects greater than 10 mm being autologous nerve grafts; however only around 40% of the 2 million US PNS patients each year regain normal function. In addition, nerve grafts have been particularly ineffective at repairing critical-size nerve defects (>3 cm). Moreover, secondary surgeries are required to harvest donor tissue, resulting in high probabilities of losing sensor and motor function at donor sites. Scaffold-based strategies where a tubular nerve guidance channel (NGC) is used to bridge the nerve defect have been promoted as a potential alternative that could avoid these additional surgeries and associated donor site morbidity. However, current NGCs lack patient-specific tunability and are only approved for small-gap (< 3cm) injuries by the U.S. Food and Drug Administration (FDA). Current research efforts are focused on creating more complex NGCs that can support regeneration of critical-size defects.

Our research seeks to use additive manufacturing technologies to create bioactive and cellular NGCs on demand for the repair of critical-size nerve defects. Recently, 3D printing has been increasingly used in research and medical therapeutics for rational, computer-aided design of biomaterial-based scaffolds with complex architecture. The NGCs should contain an outer flexible shell that seeks to mimic the mechanical properties of the surrounding biological tissue and enable diffusion of nutrients to support encapsulated cells. The use of biodegradable block copolymers with both hydrophilic and relative hydrophobic functions can provide a flexible, partially-hydrated, biocompatible and bioresorbable NGC shell. Thermoplastic elastomers (TPEs), which melt and flow above a critical temperature, turn into flexible solids upon cooling, and can be 3D-printed in a scalable fashion are reliable candidates for NGCs. This class of materials works by creating triblock copolymers where the end blocks can phase separate into hard domains from the flexible center block at lower temperatures to lock-in an elastic structure.

A-B-A type triblock copolymers of PLLA-PEG-PLLA were synthesized using varied ratios of PEG as hydrophilic groups and PLLA as hydrophobic groups. The resulting block copolymers were characterized with gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and nuclear magnetic resonance (¹H NMR) to determine molecular weight, polymer structure, and thermal behavior. GPC results showed increasing molecular weights and decreasing polydispersity with increasing PLLA concentration in the reactor, indicating longer copolymer chains were synthesized. DSC results showed that increasing PEG block length increased the melting temperature, while increasing PLLA block length led to a decrease. Groups with melting temperatures above body temperature (37 °C) and lower melting enthalpies appropriate for 3D printing were identified. In addition, equilibrium water content, degradation rates, mechanical properties, and cell response were all evaluated and correlated to polymer structure. The results indicated that these are promising materials with high tunability that can enable patient-specific and scalable production of NGCs on-demand and on-site for the treatment of peripheral nerve injuries.

Key words: Poly (L-lactic acid); Poly (ethylene glycol); Thermoplastic Elastomers (TPEs); Peripheral nerve repair