Flexor Tendon Tissue Engineering
We are developing clinically-translational paradigms in tissue engineering of flexor tendons, whose injuries are frequently associated with debilitating adhesions. We developed the first mouse model of flexor tendoplasty and associated with this model, we developed an elegant, reproducible biomechanical measure of the adhesions which we coined the
Gliding Coefficient. The mouse model enables mechanistic insights into the etiology of the adhesions following tendoplasty and tissue engineered reconstruction. We are now poised to gain better insight into the molecular etiology of adhesions by utilizing transgenic mouse models of loss and gain of function. We have also been investigating a novel alternative paradigm in tissue engineering in which freeze-dried tendon allograft can be processed for gene delivery in our mouse flexor tendoplasty model. This is a simple, yet innovative paradigm as it uses the clinically-acceptable biological graft as an acellular scaffold for drug delivery by exploiting its innate hydrophilic property, and avoids the challenges associated with implanting cells and man-made biomaterials. We demonstrated, for the first time, that the Growth and Differentiation Factor 5 (GDF5) has anti-scarring effects, in addition to its established role in tendon development and repair. In vitro models of scar tissue comprising tenocyte-seeded collagen I/III gel are currently being used to investigate the hypothesis that GDF-5 suppresses TGF-β1 and rescues MMP gene expression and scar remodeling. Our approach epitomizes interdisciplinary research as it involves engineering, molecular biology, gene therapy, and biomaterial processing concepts and techniques. The broader impact of our research is that our paradigm is potentially translatable to other tissue models such as cartilage, meniscus, and intervertebral disc.
The Concept of the Therapeutically-Endowed Freeze-Dried Tendon Allograft. Tendon and ligament allografts can be loaded, by virtue of their innate hydrophilic properties when freeze-dried, with gene delivery vectors or recombinant or tissue-derived growth factors and potentially used in reconstruction of the Anterior Cruciate Ligament (ACL), Achilles Tendon (AT) and the supraspinatus
rotator cuff tendon among other applications.