Repair of the injured spinal cord by implantation of a synthetic degradable block copolymer in rat

Abstract

The present study is designed to assess the properties of a new degradable PLA-b-PHEMA block copolymer hydrogel and its therapeutic effectiveness after implantation following a thoracic spinal cord hemisection on rats. Degradable characteristics and porous aspect of the scaffold are respectively analyzed by the evaluation of its mass loss and by electron microscopy. The biomaterial toxicity is measured through in vitro tests based on motoneuron survival and neurite growth on copolymer substrate. Functional measurements are assessed by the Basso, Beattie and Bresnahan (BBB) and the Dynamic Weight Bearing (DWB) tests during 8 weeks post-surgery. Histological analyses are achieved to evaluate the presence of blood vessels and axons, the density of the glial scar, the inflammatory reaction and the myelination at the lesion site and around it. The results indicate that the synthetic PLA-b-PHEMA block copolymer is a non-toxic and degradable biomaterial that provides support for regenerating axons and seems to limit scar tissue formation. Additionally, the implantation of the porous PLA-b-PHEMA scaffold enhances locomotor improvement. The observed functional recovery highlights the potential benefits of plain tissue engineering material, which can further be optimized by bioactive molecule functionalization or transplanted cell encapsulation.

Gene expression analysis at multiple time-points identifies key genes for nerve regeneration

“…Peripheral nervous system (PNS) injuries caused by compression, entrapment, or ischemia can lead to functional limitations that can severely affect quality of life . Even when PNS regeneration is complete, the lost function is rarely entirely restored . Regeneration failures include uncontrolled branching of newly sprouted axons and erroneous connections between axons and target organs.…”

Recent advances in synthetic polymer based hydrogels for spinal cord repair

“…Reproduced from Ref. [71] with permission from Elsevier. a perfectly fitted platform for promising combinatory strategies.…”

“…However, such biomaterials are too rigid to be implanted into soft neural tissues as they are. Therefore, in a very recent study, we synthesized a PLA-b-PHEMA block copolymer hydrogel in order to benefit from the complementary properties of PHEMA and PLA that are, respectively, softness and degradability [71]. We opted for a block copolymer design, as a physical blending of the two incompatible homopolymers would only result in a non-valid biomaterial displaying a macrophase separation.…”

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

“…[22][23] Tissue engineering represents a promising approach for modulating the inhibitory environment of the SCI lesion site to facilitate recovery. Other investigators have used a variety of biomaterials in SCI as injectable, nonstructured delivery vehicles after partial lesions such as hemisection, [24][25][26][27][28][29] contusion, or compression injury. 30,31 These incomplete lesion models spare a degree of CNS tissue at the injury site, thus in these models it is difficult to differentiate between true regeneration and distal axonal sprouting or remodeling.…”