While bone morphogenetic proteins (BMP) have demonstrated extraordinary potential in bone formation, their clinical applications require supraphysiological milligram-level doses, leading to undesired ectopic bone and cyst formation. We are developing alternative osteoinductive growth factor strategies that can effectively complement BMP activity. We intrinsically stimulated BMP expression in cells by downregulating potent secreted BMP antagonists using an RNAi strategy. We subsequently enhanced the potency of endogenous BMPs by delivering (a) exogenous BMPs at a significantly reduced dose, (b) osteoinductive signals that are more specific and less pleiotropic than BMPs, and (c) small molecules that enhance BMP signaling.

Customized biomimetic scaffolds

Design and fabrication of patient-specific, highly customizable scaffolds is attractive to direct three-dimensional tissue ingrowth for the repair of large, complex, multi-tissue defects. We are developing a novel computer-designed, biomimetic scaffolding system to repair large, complex bone defects. This system consists of three-dimensional polymer scaffolds with well-defined geometries on the macro- and micro-scales created from a printing technique in conjunction with biomimetic processing strategy to confer bone mineral-mimicking apatite microenvironment and osteogenic signaling molecules.

Injectable hydrogel systems

Injection of precursor cells or therapeutic proteins would be an ideal route of administration to the target area, circumventing the need for any surgical incisions. In this context, we are developing injectable formulations of living cells and bioactive molecules using photopolymerizable chitosan that allows gelation in situ in physiological conditions upon exposure to visible blue light. This system is currently being tested in vitro and in animal models for potential use in the treatment of degenerated joints (e.g. osteoarthritis of temporomandibular joint).

Controlled release

Direct therapeutic applications of drug molecules require high doses and repeated injections of protein drugs due to their rapid degradation in the body. Our research interests are in the development of injectable/implantable systems for the delivery of therapeutic molecules in a sustained, combinatorial, or sequential manner. We are currently applying these systems to engineer a variety of tissue types, including bone, cartilage, smooth muscle, and maxillofacial tissues.