Controlled release of Docosahexaenoic acid with nanofiber membranes for spinal cord injury treatment

In this proposed project, we aim to develop the nanofibrous membrane and scaffold with sustained drug delivery to promote the spinal cord regeneration. Therefore, this proposed application fits in the research fields listed in Form Section I: 6-2 Tissue engineering & Regenerative Medicine, and 6-3 Nano-medicine. Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. These neurological diseases cause great burden for the individual, families and society. Although surgical interventions which include early spinal decompression and stabilization surgery have some beneficial effect, current treatments for SCI have limited effect. However, current research are trying to find effective therapies for SCI. The current research theme can be categorized into neuroprotection and/or neuroregeneration. Neuroprotective therapies focus on impeding or preventing further progression of the secondary injury, whereas neuroregenerative therapies lay emphasis on recovering the lost or impaired functionality by repairing the damaged neuronal circuitry of the spinal cord. Several studies from our group（Professor Michael-Titus group） and other laboratories have shown that docosahexaenoic acid (DHA), an essential omega-3 fatty acid can induce marked improvement after traumatic injury of the central nervous system. These studies demonstrate DHA not only has the ability of neuroprotection but also neuroplasticity-promoting effect on SCI. However, for clinical translation, it is essential to develop a route to release the DHA sustainably and limit DHA against oxidation. Recently, some studies demonstrate that encapsulating DHA with nanofibers or nanoparticle is an ideal transportation method for DHA in both food engineering and cancer treatment. It is therefore promising to develop nanofibrous biomaterial associated with DHA for SCI treatment. Furthermore, the nanofibers are more similar to the size scale and architecture of the natural extracellular matrix within the spinal cord. The aligned nanofibers can display appropriate capabilities of guiding neurite direction and cellular alignment. Functionalization of the nerve scaffolds can normally be enhanced by the addition of biomolecules as drug delivery systems. Furthermore, our proposed nanofibrous membrane enable two different type of therapeutic agents or bioactive materials to be incorporated in core-shell nanofibrous structure by co-axial electrospinning process. The nanofibers can also be characterized as a 3-dimension structure scaffold that contains cells, which can structurally and neurochemically bridge the nerve lesion. Therefore, these features provide electrospun nanofibers tremendous potentials for spinal cord repairing. In our proposed study, we will incorporate tissue engineering, pharmacology and cell biology to develop a biodegradable, three-dimensional aligned nanofibers membrane with sustained DHA and neurotrophic factor delivery to provide a biofunctionalized platform, enabling a potential SCI treatment.

Project ID:PG10701-0010
External Project ID:NHRI-EX107-10715EC