| Description |
Spinal cord injury (SCI) is extremely debilitating to patients and costly to our healthcare system. Since it is an important contributor to mortality and morbidity, various therapeutic strategies have been investigated, either experimentally or clinically, to improve patients' quality of life. Studies utilizing pharmacological methods to mitigate the inhibitory components of the glial scar and facilitate axonal regeneration have been the primary experimental approaches in the field. However, the results are still not satisfactory. In this research, we aimed to tackle the issue from a novel perspective by developing cell derived, tissue engineered biomaterials that can be used in combination with other therapeutic approaches to improve the efficacy of current treatments. In this dissertation, a simple method to create either cellularized or acellular ECM biomaterial constructs is described. In particular, by utilizing patterned surface ligands, organized orientation can be introduced to the entire astrocyte derived construct morphologically and with regard to its associated matrix proteins, which mimics the native astrocyte framework within the spinal cord fiber tracts and provides these constructs the ability to guide axonal regeneration in vitro. In addition, meningeal fibroblast based biomaterial constructs are also developed taking advantage of the same engineering approach. It has been demonstrated that repairing damaged dura mater with allografts also benefits the regeneration process of the damaged spinal cord. In particular, acellular meningeal ECM constructs preserve a similar matrix protein profile as the native rat dura mater and support allogeneic meningeal cell adhesion and promote proliferation. The results suggest these engineered biomaterial constructs derived particularly from cells residing within tissue targeted for repair may carry appropriate tissue specific biological cues and hold therapeutic potentials for spinal cord injury repair as well as dual defect reconstruction. |
