Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat

Abstract

Positively charged oligo[poly(ethylene glycol) fumarate] (OPF+) scaffolds loaded with Schwann cells bridge spinal cord injury (SCI) lesions and support axonal regeneration in rat. The regeneration achieved is not sufficient for inducing functional recovery. Attempts to increase regeneration would benefit from understanding the effects of the scaffold and transplanted cells on lesion environment. We conducted morphometric and stereological analysis of lesions in rats implanted with OPF+ scaffolds with or without loaded Schwann cells 1, 2, 3, 4, and 8 weeks after thoracic spinal cord transection. No differences were found in collagen scarring, cyst formation, astrocyte reactivity, myelin debris, or chondroitin sulfate proteoglycan (CSPG) accumulation. However, when scaffold-implanted animals were compared with animals with transection injuries only, these barriers to regeneration were significantly reduced, accompanied by increased activated macrophages/microglia. This distinctive and regeneration permissive tissue reaction to scaffold implantation was independent of Schwann cell transplantation. Although the tissue reaction was beneficial in the short term, we observed a chronic fibrotic host response, resulting in scaffolds surrounded by collagen at 8 weeks. This study demonstrates that an appropriate biomaterial scaffold improves the environment for regeneration. Future targeting of the host fibrotic response may allow increased axonal regeneration and functional recovery.

Regenerative Therapies for Spinal Cord Injury

“…47 Combinations of these are also being investigated. 16,[36][37][38][48][49][50][51] Nevertheless, only one biomaterial has reached clinical trials, 52 while most remain in preclinical animal 43,[53][54][55][56] or in vitro stages of investigation. 57,58 Even developed therapies with potential for clinical translation still require extensive testing to prove their safety and efficacy in patients.…”

Controlling the Surface Chemistry of a Hydrogel for Spatially Defined Cell Adhesion

“…We chose to focus on the surface chemistry of oligo-(polyethylene glycol) fumarate (OPF 5 ) because of its potential for use in neural regeneration devices. 15 It is an especially challenging substrate in that it is devoid of functionality for covalent attachment of surface adducts; it is replete, though, with oxy and carbonyl groups capable of metal ion complexation. 29−32 Partially dehydrated, 0.08 mm thick, friable sheets of OPF were provided by Dr. Michael Yaszemski and Nicholas Madigan (Mayo Clinic, Rochester, MN); they swell on rehydration in Milli-Q water (under these conditions, a 4 mm × 4 mm coupon of "dry" OPF swells to about 12 mm × 12 mm).…”

Targeting connexin 43 expression via scaffold mediated delivery of antisense oligodeoxynucleotide preserves neurons, enhances axonal extension, reduces astrocyte and microglial activation after spinal cord injury

“…Subsequently, based on an established protocol, a region of interest within 500 µm from the glial scar border was demarcated. 37 Using ImageJ, a freehand line was drawn along the glial scar border and this line was then translated 500 µm away from the scaffold. The region flanked within these two lines was defined as the region of interest where the following equation was applied:…”