(648c) 3D Printing of Nerve Guidance Channels for Peripheral Nerve Repair

The peripheral nervous system (PNS) is a complicated and extensive network of nerves that are the means by which the brain and spinal cord control the rest of the body. The PNS is fragile and can be easily damaged by injuries or trauma. Surgical treatment is the only remedy currently available, with the gold standard for defects greater than 8 mm being autologous nerve grafts; however only around 40% of the 1.8 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).¹ 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 the additional surgeries and associated donor site morbidity involved in the harvest of nerve grafts.² Clinicians have thus increased the use of NGCs combined with current surgical therapeutics. 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.

In this context, 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. Furthermore, printing with co-axial extruders can enable the direct printing of layered tubular structures for use as NGCs. 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.

In this study, an A-B type diblock copolymer of poly(ethylene glycol) methyl ether (mPEG) combined with poly(l-lactide) acid (PLLA) and another A-B-A type triblock copolymer of PLLA-PEG-PLLA were synthesized using varied ratios of mPEG, PEG and PLLA. The resulting block copolymers of mPEG-PLLA and PLLA-PEG-PLLA containing different lengths of the PLLA hydrophobic chain were characterized with gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) to determine molecular weight, polymer structure, and thermal behavior. In addition, equilibrium water content, degradation rates, and cell response were all evaluated and correlated to polymer structure. With the 3D printing of copolymers using coaxial printing needles, a scalable process for the production of cellular NGCs could be developed.

References

1. Burkhard Schlosshauer, L.D., et al., Neurosurgery, 59 (2006), 740-748.

2. Cinteza, D., et al., Maedica – A Journal of Clinical Medicine, 10:1 (2015), 65-68.