Research Projects

Chronic back pain due to lumbar intervertebral disc (IVD) degeneration is a significant global issue, affecting millions of the aging population and causing a severe economic burden. Current surgical interventions fail to target the root cause of the underlying pathogenesis, mainly at the disc nucleus, making it difficult to slow or reverse disc degeneration and associated disabilities. This leads to the search for a minimally invasive disc replacement strategy that conforms to the native IVD anatomy while recapitulating the glycosaminoglycan-rich matrix composition, cellularity, and mechanical function. The degenerated disc presents an intricate microenvironment that is challenging to repair due to the degradation of aggrecan, a key proteoglycan that confers water retention and weight bearing attributes to IVD. Loss of aggrecan triggers inflammatory response and migration of blood vessels/neurons, leading to secondary events like disc herniation and sciatica. This proposal aims to create an artificial aggrecan analog (aAC) covalently tethered to hyaluronic acid (HA) chains via photo-initiated glycidyl methacrylate crosslinking to form large polyanionic aggregates (HA-aAC) resembling the native IVD matrix architecture and composition. The developed hydrogel will be characterized for its structural, chemical, and mechanical resemblance to native IVD tissue. The efficacy of microencapsulated MSCs in facilitating disc regeneration will be screened for increased expression of matrix components and diminished expression of proteolytic enzymes.