Biomimetic Materials and Drug Delivery
Dr. Lee’s research focuses on the design and development of new biomaterial systems to provide fundamental bases and translational approaches to tissue engineering and regenerative medicine. Specific areas of interest are orthobiologics, material-based therapeutics to repair craniofacial and orthopedic skeletal defects, novel liposomal platform for drug and gene delivery, photopolymerizable hydrogel systems.
New therapy for bone repair
Although bone morphogenetic protein-2 (BMP-2) is believed to be the most potent osteoinductive factor available for bone repair, its clinical application requires supraphysiological BMP doses that increase inappropriate adipogenesis and cyst-like bone formation. We developed alternative biomolecular strategies that can promote pro-osteogenic activity of BMPs while simultaneously suppressing their adverse effects by regulating expression of Trb3, a positive regulator of BMP signaling and a negative regulator of adipogenesis. Upon BMP stimulation, however, BMP efficacy is greatly reduced due to the enhanced expression of natural BMP antagonists to auto-regulate endogenous BMP-2 levels. Thus, the potency of Trb3 in BMP treatments can be enhanced by inhibiting expression of BMP antagonists such as noggin. Successful completion of these studies will identify a new strategy to improve clinical efficacy and safety of current BMP therapeutics by regulating expression of Trb3 and noggin for enhanced bone repair.
Funding agency: National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Dental and Craniofacial Research (NIDCR)
Nanomaterials for controlled release
Therapeutic efficacy of drug molecules is affected by delivery kinetics and requires large drug concentrations due to their intrinsic instability and rapid degradation in the body. Sterosomes are recently developed types of nonphospholipid liposomes formed from single-chain amphiphiles and high content of sterols. Although sterosomes presented significantly increased stability compared to conventional phospholipid liposomes, current sterosome biomaterials are not truly bioactive and have no intrinsic therapeutic effects. We developed a novel sterosome formulation with osteoinductive properties by an effective selection of sterol, one of the sterosome components. Our innately osteoinductive liposomal platform will be useful for delivery of small molecular drugs and/or other therapeutic genes for enhanced bone formation.
Funding agency: Department of Defense (DOD), Congressionally Directed Medical Research Programs (CDMRP)
Hydrogel carrier system
Hydrogels derived from naturally occurring polymers are attractive matrices for tissue engineering by delivering precursor/stem cells or therapeutic agents into defect sites through a minimally invasive manner. Tuning hydrogel degradation is a critical factor for successful tissue regeneration to allow close cell-cell interactions and ECM formation. We have selected a unique enzyme-substrate pair as a hydrogel, where the hydrogel is designed with photocrosslinkable chitosan and lysozyme. Our study demonstrated that the enzyme-functionalized hydrogel successfully modulated the degradation rates of the hydrogel and aspects of cellular behavior and supported functional tissue formation.
Funding agency: Musculoskeletal Transplant Foundation (MTF)