Current Projects
IGF-1 Gene Therapy to improve Knee Ligament Healing
The ultimate goal of Insulin-like Growth Factor-1 (IGF-1) gene based delivery is to produce therapeutic protein in sufficient quantity at the appropriate site to promote a physiological response. A main advantage of cell-based gene therapy over exogenous systemic delivery of hormone or growth factor is that the application of the therapeutic factor can be site directed and concentrated to the injured area, thus eliciting a maximal response to the therapeutic factor. The adeno-associated virus containing the therapeutic factor is introduced into cells outside the animal, and re-introduced back into the animal at the target site. The method offers several advantages to other therapies, such as in vivo gene therapy, including improving transfection efficiency, better targeting of specific cell types and the capacity to measure the effects of the genetic modification on the cells before introducing them into the animal. The primary objective of this research is to use IGF-1 as potential endogenous countermeasure to positively modulate medial collateral ligament (MCL) wound healing. NASA, NIH and the Department of Defense has recently expressed a great interest in wound repair in Astronauts during spaceflight (NASA), normal orthopaedic ligament and tendon injuries (NIH-NIAMS) and returning the wounded soldier back to the field (DoD) and are currently seeking viable treatment countermeasures to improve wound repair processes, and decrease recovery times without compromising the integrity of the tissues.
Low Level Laser Irradiation and ECM function
Recently, the field of photobiology has gained notice, particularly the positive effects of Low Level Laser Irradiation (LLLI) on wound healing in cutaneous tissues and in rodent ligament healing investigations. Single doses of LLLI therapy using a gallium aluminum arsenide laser (660nm, 8.8 mW) to treat medial collateral ligament (MCL) surgical disruptions in rodents improved ligament stiffness within three to six weeks after surgery. Similarly, single and multiple bouts of laser therapy improved MCL strength, stiffness and increased collagen fibril diameters at the scar site suggesting that LLLI enhances one or more of the processes of wound repair in the damaged tissues. Our research utilizes a LLLI treated cell culture model to eliminate the systemic effects of other tissues and organs (i.e. muscle, liver, etc.) and allow us to specifically examine connective tissue fibroblasts and the cellular responses which mediated inflammation and wound healing.
CTPL Cardiovascular Research
Our laboratory has been interested in the ECM regulation in the heart. We have published one peer reviewed manuscript (Martinez, D.A., et al., Extracellular matrix maturation in the left ventricle of normal and diabetic swine. Diabetes Res and Clin Pract 59 (1) 1-9, 2003.) and obtained funding in 1998-2003 for an American Heart Association Grant entitled, "Adaptive Cardiac Connective Tissue Remodeling Through Directed Delivery Into Cardiac Myo-fibroblast Cells." Our research interests in ECM regulation of connective tissues can be easily adapted to the heart and peripheral vasculature. Catabolic, as well as anabolic pathways, in the heart, are important in maintaining the cardiac structure and function and are very important in cardiac wound repair and tissue regeneration. The biochemical and molecular analyses of cardiac ECM proteins and genes are routinely assayed in our laboratory.