Biodegradable Polymer Scaffolds in Spinal Cord Regeneration

Biodegradable polymers are being investigated as scaffold materials for tissue regeneration, including neural regeneration.

Spinal cord injury is no laughing matter. According to the National Spinal Cord Injury Statistical Center, it’s estimated that there are 273,000 people with spinal cord injury in the United States, with 12,000 new cases every year.

Spinal cord injury involves damage to the blood-brain barrier, followed by infiltration of immune cells and secondary damage involving necrosis and eventual formation of glial/connective tissue scarring, which acts as a physical barrier to axonal regeneration. There are no efficient approaches yet to central nervous system regeneration that would result in a therapy for chronic spinal cord injury. Although axons in the peripheral nervous system are known to regenerate, the glial scar microenvironment, i.e., myelin debris, is believed to prevent regeneration of the central nervous system.

A Role for Polymers?

Hypothetically, promoting axonal regeneration inside a biodegradable polymer scaffold — bypassing the glial scar area — would help restore function of a damaged spinal cord. Biodegradable polymers are being actively investigated as scaffold materials for a variety of medical applications and tissue regeneration, including neural regeneration. In this case, a biodegradable scaffold would offer an alternative route for the neurons to regrow.

To find an appropriate scaffold material, one would first need to address the issues of polymer biocompatibility, neuronal survival, and axonal growth. To determine suitability for spinal scaffolds, researchers from the University of Porto, Portugal, have evaluated three biodegradable candidate polymers:

  • Poly(ε-caprolactone)
  • Poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) (11:89 mol%)
  • Poly(trimethylene carbonate)

They tested films prepared from these polymers, coated with poly(L-lysine)(PLL)  — which creates additional hydrophilic biocompatible layer — for neuronal cell adhesion and neurite outgrowth. They found that neuronal polarization and axonal elongation was significantly higher on polycarbonate-caprolactone films. After cortical neurons were cultured on polycarbonate-caprolactone films, they were able to extend neurites even when seeded onto myelin. The results of their work have been published in PLoS One, an open-access scientific journal:

This work shows that P(TMC-CL) with a high CL content can promote axonal regeneration, prompting neurons into a regeneration mode, even under inhibitory conditions. This effect is mediated by the GSK3β signaling pathway, which is triggered by P(TMC-CL)’s surface mechanical properties. P(TMC-CL) being a material that can been processable in a variety of shapes and forms, including porous conduits and electrospun fibers, it presents itself as a valuable tool in the design of new strategies for application in the treatment of spinal cord lesions, while supporting axonal growth and taming myelin dependent neurite outgrowth inhibition without the need of the administration of any therapeutic drug.

Trial Underway

Previously, the electrospun fibers of this copolymer, poly(trimethylene carbonate-co-ε-caprolactone, were studied for drug delivery of ibuprofen, with the goal of limiting initial inflammatory response in a spinal cord lesion. Generally speaking, acute spinal cord injuries offer more possibilities for treatment before secondary damage takes place. To treat acute spinal cord injuries, poly(lactide-co-glycolide) biodegradable scaffolds, seeded with neural stem cells have been proposed by InVivo Therapeutics, a medical device company in a Cambridge, Mass. The company received approval from FDA for the First Human Trial Using Biomaterials for Traumatic Spinal Cord Injury last year, and the trial is now underway. We’ll be waiting for the results with hope!

Image by lightwise/123RF.
Source: National Spinal Cord Injury Statistical Center (NSCISC), nscisc.uab.edu.
Source: “Poly(Trimethylene Carbonate-co-ε-Caprolactone) Promotes Axonal Growth,” by Daniela Nogueira Rocha, Pedro Brites, Carlos Fonseca, and Ana Paula Pêgo, PLoS One, 2014, 9(2):e88593, doi: 10.1371/journal.pone.0088593, February 27, 2014.
Source: “Ibuprofen-loaded Poly(trimethylene carbonate-co-ε-caprolactone) Electrospun Fibres for Nerve Regeneration,” by Liliana R. Pires, Vincenzo Guarino, Maria J. Oliveira, Cristina C. Ribeiro, Mário A. Barbosa, Luigi Ambrosio, and Ana Paula Pêgo, Journal of Tissue Engineering and Regenerative Medicine. doi: 10.1002/term.1792, August 16, 2013.
Source: Published Research, invivotherapeutics.com.
Source: “InVivo Therapeutics to Move Forward With Its First Clinical Trial After Receiving FDA Conditional Approval,” invivotherapeutics.com.