Injectable cartilaginous template transformed BMSCs into vascularized bone

Abstract

Regeneration of alveolar bone for dental implant remains a major issue, partifcularly for patients suffering from severe bone adsorption and irregular socket trauma. Recapitulating embryological development is becoming an attractive approach for engineer organ or three-dimensional tissues from stem cells. In this study, we aimed to develop an injectable "cartilaginous" graft with adequate mechanical resistance and ideal bone remodelling potential. The cartilaginous graft was composed of a particulate decellularised cartilage matrix (PDCM), chondrogenically primed bone mesenchymal stem cell (BMSC) bricks (CB), and enriched platelet-rich plasma (P) gel. In immunodeficient mice, we found that angiogenesis occurred quickly inside PDCM-CB-P constructs after implantation, thereby improving tissue survival and bone formation. In rabbit tibia bone defects around implants, we confirmed that CBs not only transformed into bone tissue rapidly, but also significantly promoted bone remodelling and replacement of PDCM, thus realising osseointegration of dental implants within 3 months. In conclusion, CBs exhibited the potential for endochondral ossification in vivo, and application of a cartilaginous template composed of PDCM, CB, and P provided a minimally-invasive, "free material residual" approach to regenerate alveolar bone tissues in vivo. This method could have applications in peri-implant bone regeneration.