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.

GDNF Schwann cells in hydrogel scaffolds promote regional axon regeneration, remyelination and functional improvement after spinal cord transection in rats

“…The extracellular matrix of the injury site lacks guidance cues to promote cell survival and axon outgrowth through an injury field that contains inhibitory molecular cues. Polymer scaffolds may reduce these barriers and provide a multimodal approach to bridge the gap and approximate viable tissue with structured order (Madigan et al, ; Hakim et al, ). They serve as a matrix to guide axonal growth through the area of injury.…”

A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation

“…This is most likely to be due to their effect on cell morphology, which has been shown to directly influence osteogenic versus adipogenic differentiation . Producing scaffolds that significantly enhance differentiation toward one lineage whilst inhibiting that toward others could prevent failure of generated tissue due to fibrosis, unwanted fatty tissue formation or ossification …”

A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury

“…Besides the absence of spontaneous recovery in untreated animals, some authors failed to observe functional motor recovery in injured rodents treated with scaffold-based strategy. 28,36,37 In all abovementioned studies a segment resection model was utilized. It was suggested that the absence of recovery of hindlimbs function in animals subjected to complete spinal cord transection was likely due to insufficient axon regeneration and integration in functional circuit.…”