(194j) Synthesis and Characterization of PLLA-PEG-PLLA Triblock Copolymers As Biodegradable Thermoplastic Elastomers for Peripheral Nerve Repair

Synthesis
and Characterization of PLLA-PEG-PLLA Triblock Copolymers as Biodegradable
Thermoplastic Elastomers for Peripheral Nerve Repair

ABSTRACT

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, A-B-A type triblock
copolymers of PLLA-PEG-PLLA were synthesized using varied ratios of PEG and
PLLA. The resulting block copolymers 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, mechanical
properties, and cell response were all evaluated and correlated to polymer
structure.

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