Connective tissue regeneration

Dr. Lane's laboratory effort is primarily directed toward regenerating bone and other connective tissues following injury. The laboratory utilizes animal models to simulate osseous defects both in the spine and long bones. Methods employed by the group include microsurgery, molecular biology, tissue culture, biochemical assays of bone formation, histology (undecalcified, in situ hybridization, immunohistology), quantitative radiography, biomechanical testing, and blood flow analysis.

The study of osteogenesis includes the evaluation of bone marrow and ex vivo explanted mesenchymal stem cells. Osteoconductive experiments center on biodegradable polymers, native biosynthetic and composite ceramics, and collagen based matrices. Osteoinduction uses the family of BMP growth factors as well as BFGF and TGF-ß. Bone morphogenctic protein has been studied during fracture healing by in situ hybridization and immunohistology. We have employed the use of exogenous rhBMP to heal critical defects, promote spine fusion and generate bone ossicles. In association with Dr. Weiland we are currently generating "bones to order" in silastic molds containing mesenchymal stem cells, BMP, and a vascularized pedical. These neo-bones can be moved an their vascular leash or through micro-vascular transer to replace or heal apendicular bone defects. Through viral vectors BMP and other growth factor genes have been infected into stem cells to be used regionally to repair connective tissue. The laboratory, in collaboration with Dr. Bostrom and Dr. Sandhu, is actively using BMP, osteoprogenitor cells, and a variety of osteoconductive matrices in animal and human clinical trials.

The laboratory is examining the process of injury and repair of connective tissues. By utilizing Y-chromosome and transfected cells, we are determining the origin of the specific stem cells that contribute to the various stages of tissue regeneration and differentiation. The osseous matrix of normal and metabolically altered bone is studied in collaboration with Dr. Boskey and Dr. Paschalis principally by FTIR micro-spectroscopy and collagen analysis. We are evaluating how estrogen and other gender specific hormones control the quality and amount of collagen in tendons and ligaments.

Working in collaboration with Dr. Bostrom and Dr. Nestor, the laboratory is establishing the role of various cytokines in the pathway of prosthetic loosening. We are utilzing specific bone anti-resorptive agents to inhibit the osteolytic process.