Endochondral bone tissue engineering: using cartilage to drive vascularized bone regeneration (87.6)

Abstract

There is a significant unmet clinical need to develop improved strategies to promote vascularized bone regeneration. Current bone graft technologies promote repair through direct osteogenesis by use of auto‐ or allografted bone. Critical failures associated with these therapies include osteonecrosis and poor osseointegration. The long‐term goal of this project is to develop a tissue engineering approach to promote endochondral bone formation, in which bone forms through a cartilage intermediate. Endochondral ossification is the normal mechanism by which long bones form and the majority of fractures heal. By leveraging this normal healing response, we hypothesize we can overcome the clinical problems of osteonecrosis and poor integration to produce a vascularized and integrated bone regenerate. To test this hypothesis, critical sized defects were created in mid‐diaphysis of murine tibia. Defects remained empty, or were filled with a cartilage graft, autograft or allograft bone. Our data show cartilage grafts effectively transformed into vascularized bone and integrated with the host bone to perform statistically better than allografts and equivalent to autografts. To translate this therapy we have developed a biomimetic acrylated hyaluronic acid hydrogel that contains peptide sequences for cell attachment (bone sialoprotein‐derived RGD), heparin for modulation and sequestration of growth factors, and enzymatically degradable MMP‐13 crosslinks. Hypertrophic chondrocytes encapsulated in these scaffolds mineralization during in vitro culture in basal medium. In ongoing work, these scaffolds have been transplanted into a subcutaneous model of osteonecrosis to evaluate the capacity to re‐vitalize bone. This novel approach to bone tissue engineering has the potential to improve clinical outcomes in bone regeneration.Grant Funding Source: Supported by NIH 5F32AR062469 (CSB), MTF Junior Investigator Award (CSB), UCSF CTSI Award (CSB)