Melissa Jane Walker, Indiana University School of Medicine, Stark Neurosciences Research Institute, Indianapolis, USA

Novel Bioengineered Hydrogel Combinational Therapy for Traumatic SCI

Funded in: 2013, 2014, 2015

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Problem: The tissue damage and the formation of a cystic cavitation following spinal cord injury

Target: Bridge the lesion for axon regeneration a growth-permissive tissue scaffold

Goal: A combinational treatment based on a non-immunogenic, in-situ gelable hydrogel containing nanoparticles embedded with two trophic factors to improve regeneration

Spinal cord injury (SCI) is devastating and debilitating, and currently no effective treatments exist. The primary trauma disrupts the neural tissue and the local vasculature and is followed by secondary damage leading to neuronal death, axonal degeneration, and glial scar formation in many cases accompanied by the formation of a cystic cavitation. One approach to bridge the lesion for axon regeneration is the implantation a growth-permissive tissue scaffold.

Bioengineered tissues have great potential to promote axonal regeneration and angiogenesis after CNS injuries. Novel bioengineered hydrogel can be combined with diffusible, regeneration promoting molecules that are released in the lesion. Preliminary data of the Dr. Walker showed that transplantation of novel bioengineered hydrogel releasing the trophic factor GDNF (glial cell line-derived neurotrophic factor) into the lesion site significantly improved tissue sparing and functional recovery following a clinically relevant contusive SCI.  

The project aims to characterize the biological activity of a new non-immunogenic, in-situ gelable hydrogel containing nanoparticles embedded with two trophic factors, GDNF and VEGF (vascular endothelial growth factor).

In different experimental groups of a clinically relevant SCI model Dr. Walker will investigate the effects of the hydrogel containing nanospheres that release GDNF and VEGF alone or in combination. The different groups of animals will be tested for

  • functional recovery
  • histological changes (as lesion and cavity measurements, motor neuron counts, vascular reorganization, axonal growth, glial scar, inflammation, and myelination).

A further aim will be to apply the most effective combinational treatment out of these experiments and add a trophic factor gradient to direct axons to leave the distal end of the lesion and enter the tissue caudally, to form functional synapses, for improved functional recovery.