Characterization of Tissue-Engineered Human Periosteum and Allograft Bone Constructs: The Potential of Periosteum in Bone Regenerative Medicine

Abstract

Delayed-union or non-union between a host bone and a graft is problematic in clinical treatment of segmental bone defects in orthopedic cases. Based on a preliminary study of human periosteum allografts from this laboratory, the present work has extensively investigated the use of human cadaveric tissue-engineered periosteum-allograft constructs as an approach to healing such serious orthopedic surgical situations. In this current report, human cadaveric periosteum-wrapped bone allografts and counterpart controls without periosteum were implanted subcutaneously in athymic mice (<i>nu/nu</i>) for 10, 20, and, for the first time, 40 weeks. Specimens were then harvested and assessed by histological and gene expression analyses. Compared to controls, the presence of new bone formation and resorption in periosteum-allograft constructs was indicated in both histology and gene expression results over 40 weeks of implantation. Of several genes also examined for the first time, <i>RANKL</i> and <i>SOST</i> expression levels increased in a statistically significant manner, data suggesting that bone formation and the presence of increasing numbers of osteocytes in bone matrices had increased with time. The tissue-engineering strategy described in this study provides a possible means of improving delayed-union or non-union at the healing sites of segmental bone defects or bone fractures. The potential of periosteum and its resident cells could thereby be utilized effectively in tissue-engineering methods and tissue regenerative medicine.