Abstract
Annually in the United States, 17,000 new patients suffer a new traumatic spinal cord injury (SCI) contributing to the roughly 300,000 patients living with chronic paralysis with no clinically approved treatment options. In the clinic, therapeutic options focus on sparing, plasticity, and limiting complications rather than actively regenerating tissue. SCI results in a cascade of immune and inflammatory responses to protect the body from further damage by clearing dead cells and debris and walling off the healthy tissue with scar formation. While important for regulating the injury environment, when these responses persist, they create an inhospitable microenvironment for tissue growth, limiting any potential for repair. Functional recovery thus remains limited in patients suffering from SCI, leading to chronic paralysis, significantly altering their quality of life. Pre-clinically, biomaterials have demonstrated success in improving tissue repair by limiting cyst and scar formation, providing a synthetic extracellular matrix, and directing axon elongation through the injury, but their clinical translation has showed minor success. Biomaterials alone can only address part of the whole picture of SCI, thus resulting in a functional upper limit for repair. Actively promoting repair by delivering other therapeutics with a biomaterial in combinatorial platforms could result in further tissue repair leading to improved functional recovery post-SCI. The work presented in this thesis will advance the previously developed poly(ethylene glycol) (PEG) tubes system for SCI by combining it with cell transplantation, gene therapy, and targeted nanoparticle delivery without the need to reengineer the biomaterial platform for each new application or combination of applications.