Physical and biological performance of a novel block copolymer nerve guide

Abstract

Although the ability to regenerate is evident in the nervous system, lesioned neurites are unable to cross gaps in neuronal pathways. In order to bridge gaps, guiding cues are essential to direct neurite regrowth. To overcome many of the shortcomings of polymer-based nerve guides, we developed a bioresorbable nerve guide composed of a novel trimethylene carbonate-caprolacton block copolymer (TMC-CL). Pore formation was controlled by using special solvent/precipitation media compositions in combination with the pore forming agent poly ethylene glycol (PEG). NMR spectroscopy, shear force-, compression-, and permeation assays were used for conduit characterization. The polymer conduit has a semipermeable wall with submicron pores to allow free metabolite/drug exchange. In order to investigate the principle of temporally controlled expression of therapeutic proteins in nerve guides, Neuro-2a cells were genetically engineered to express the reporter gene product green fluorescent protein (GFP) under the control of the Tet-On system. When these transduced cells were encapsulated in nerve guides, GFP expression could be induced for days by adding the antibiotic tetracycline derivative doxycycline to the nerve guide environment. Furthermore, encapsulated dorsal root ganglia (DRG) produced long neurites in vitro. In subsequent in vivo experiments, nerve guides filled with Schwann cells (SC) were implanted into lesioned spinal cords of adult rats. Regeneration of spinal cord axons into nerve guides was promoted by co-implanted Schwann cells. The data suggest that the novel TMC-CL nerve guides provide a promising tool for neuroregeneration.

Neuro tissue engineering of glial nerve guides and the impact of different cell types

“…SCs enhance axonal growth in vitro by one order of magnitude [27], support spinal cord repair [18] and regeneration via PNS implants [51]. In a most recent approach, we have found that poly-(TMC-CL) nerve guides support regeneration of severed rat median nerves [52] and the spinal cord [21] only if nerve guides have been pre-filled with SCs. Thus, SCs have become a preferred candidate for biohybrid implants.…”

“…In some cases a drop of poly-lactide solution was employed for additional fixation. The needle allowed to easily insert all PGA filaments into a resorbable, semipermeable nerve guide conduit made of poly-trimethylene carbonate-e-caprolactone (TMC-CL) [21]. The inner diameter of the conduit was approximately 1 mm, and the thickness of the conduit wall was 100 mm.…”

A Prospective Randomized Study Comparing Woven Polyglycolic Acid and Autogenous Vein Conduits for Reconstruction of Digital Nerve Gaps

“…Current investigation is focusing on developing conduits that can actively enhance the migration of Schwann cells and axons during regeneration or that could stimulate regeneration over longer nerve gap lengths. 31,32 Over the past several years, there has been increased interest in decellularized nerve allografts. 33,34 Allografts may ultimately prove to be best: the convenience of an alloplast with the effectiveness of an autograft.…”

Carriers in Cell-Based Therapies for Neurological Disorders

“…Matrigel ® contains a number of ECM molecules and growth factors and has been used as filler for nerve guidance channels of biodegradable [137,154,155] or non-biodegradable source [66,78] and cell-encapsulating device [92] (Table 3F). Although it had superior properties in promoting neurite growth and enhancing cell survival, proliferation and functioning, Matrigel ® derivation from a sarcoma cell line source has greatly limited its potential clinical use [11].…”