In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model

• Published in: Calcified tissue international 2016-08, Vol.99 (2), p.209-223
• Main Authors: Lovati, A. B., Lopa, S., Recordati, C., Talò, G., Turrisi, C., Bottagisio, M., Losa, M., Scanziani, E., Moretti, M.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone density; Bone Substitutes - metabolism; Bone Transplantation - methods; Cell Biology; Cells, Cultured; Durapatite - pharmacology; Endocrinology; Life Sciences; Mesenchymal Stromal Cells - cytology; Original Research; Orthopedics; Osseointegration - physiology; Osteogenesis - physiology; Sheep; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-016-0140-8

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.