Tissue Engineering Bone By Recapitulating Developmental And Repair Programs Offers Improved Biological Outcomes

The principle behind tissue engineering and regenerative medicine is development of functional replacements for damaged or diseased tissues. In the case of bone, technologies focus on promoting direct osteogenesis. However, current therapies are associated with clinical drawbacks, including osteonecrosis and poor integration. Bone regeneration through endochondral ossification, which is the mechanism by which long bones form and the majority of fractures heal, may overcome these problems. We hypothesize that cartilage grafts can promote a vascularized and integrated bone regenerate. To test this, we created stabilized defects in the mid-diaphysis of the murine tibia and transplanted cartilage grafts from reporter mice. The cartilage was replaced by vascularized bone that integrated with the host. Since endochondral ossification is thought to require chondrocyte apoptosis and cartilage replacement by osteoblasts from the invading vasculature, we predicted the new bone would be host-derived. However, the new bone was composed largely of donor-derived cells and there was limited evidence of apoptosis. Together, these data suggest that in our animal model an alternative healing mechanism, such as transdifferentiation, is occurring. Translation of these data into a patient-based therapy provides a platform to improve clinical outcomes and gain insight into the biology of bone regeneration. Grant Funding Source: NIH-NIAMS (R01-AR053645-01 to TM), UCSF GEMS-CSTI Fellowship (CSB)