Stimulation of neurite outgrowth using positively charged hydrogels

Abstract

Autologous nerve grafts are currently the best option for the treatment of segmental peripheral nerve defects. However, autografts have several drawbacks including size mismatch and loss of sensation in the donor nerve's sensory distribution. In this work, we have investigated the development of a synthetic hydrogel that contains positive charge for use as a substrate for nerve cell attachment and neurite outgrowth in culture. We have demonstrated that modification of oligo-(polyethylene glycol) fumarate (OPF) with a positively charged monomer improves primary sensory rat neuron attachment and differentiation in a dose-dependent manner. Positively charged hydrogels also supported attachment of dorsal root ganglion (DRG) explants that contain sensory neurons, Schwann cells and neuronal support cells. Furthermore, charged hydrogels were analyzed for the appearance of myelinated structures in a co-culture containing DRG neurons and Schwann cells. DRGs and Schwann cells remained viable on charged hydrogels for a time period of three weeks and neurites extended from the DRGs. Sudan black staining revealed that neurites emerging from DRGs were accompanied by migrating Schwann cells. These findings suggest that charged OPF hydrogels are capable of sustaining both primary nerve cells and the neural support cells that are critical for regeneration.

Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection

“…Hydrogel tubes were made by dissolving OPF and initiator in distilled H 2 O at 37 °C for 10 min according to a previously described method [29]. After centrifugation, N-vinyl pyrrolidinone (NVP) crosslinker was added and vortexed.…”

Sustained Delivery of Dibutyryl Cyclic Adenosine Monophosphate to the Transected Spinal Cord Via Oligo [(Polyethylene Glycol) Fumarate] Hydrogels

“…Optimal cell number was based on previous SC transplantation studies. 36,[58][59][60] The same cell number was chosen for MSC delivery to make the biological comparison of MSCs to SCs more clear and significant. The scaffolds for the control animals were also prewet with cell culture medium and were loaded with Matrigel alone without any cells.…”

“…27,36 After centrifugation, N-vinyl pyrrolidinone (NVP) crosslinker was added. Ninety milligrams of microspheres was added to 1 mL of OPF solution, which was then poured into glass molds and crosslinked using UV light.…”

“…[33][34][35] Recent studies suggest applications in the nervous system using positively charged hydrogels. 36 These researchers demonstrate the capability of OPF hydrogels for sustaining growth of both primary nerve cells and neural support cells that are critical for regeneration.…”

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

“…Previous studies in our laboratory have evaluated various polymers and cell types for nervous system repair. [32][33][34][35][36][37][38][39][40][41][42][43][44] Schwann cells loaded into polymer scaffold channels have demonstrated an increased capacity for supporting axonal regeneration when compared with other cell types such as neural stem cells or mesenchymal stem cells. 37,42 We have shown that biodegradable polymer hydrogel scaffolds seeded with Schwann cells are able to bridge the growth inhibitory lesion site and support axon regeneration in vivo.…”