Incorporation of N-Acetyl Cysteine in Polyester Disulfide Materials for Spinal Cord Injury Applications

Despite advancements, the gold-standard treatment for SCIs remains invasive spine surgery. While this may provide some relief for patients, these procedures can carry significant risks for patients, including infection and further neurological complications. Additionally, surgery primarily reduces patient pain rather than alters the inflammatory response of cellular and biochemical signaling that leads to secondary damage. Given these limitations, available alternatives only address a singular neural degeneration mechanism and have had limited success in clinical trials. Thus, there is a need for an efficient, localized biomaterial that can limit secondary SCI injury by mitigating the negative signaling cascades responsible for the injury.

In response to this need, this project focuses on treating SCIs by generating a biomaterial that controllably releases simple signaling molecules (SSMs) to encourage neuroprotection. SSMs can be incorporated into monomers that are then polymerized. These degradable polymers provide localized, sustained release, mitigating secondary damage associated with nervous system injuries. In particular, N-acetyl Cysteine (NAC), an antioxidant derived from L-cysteine, was utilized to synthesize polyester disulfide material. NAC has been proposed to influence intracellular reactive oxygen species (ROS) via multiple enzymatic pathways. Studies exploring the delivery of NAC for secondary SCI damage have been limited, reducing the potential for NAC-based treatments.

This work evaluates the neuroprotective capabilities of NAC and its incorporation into a novel polymeric material to evaluate this potential. Initially, the cytotoxicity and neuroprotectant capabilities of NAC were evaluated on the NE-4C cell line utilizing dsDNA and ATP assays. Following this, an NAC-based monomer was synthesized and assessed using Nuclear Magnetic Resonance (NMR) before incorporation into multiple polyester disulfides. Polyester synthesis was achieved through transesterification involving four PEG-based diols. Subsequently, these were evaluated using NMR and gel permeation chromatography (GPC).

Currently, this research is progressing towards integrating these polyester disulfide materials into a hydrogel-based drug delivery platform. This innovative approach aims to provide a multifaceted strategy for neuroprotection in SCIs. This work yields valuable insight into the development of secondary SCI treatments and other SSM-based drug delivery platforms.