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

A. B. Lovati, S. Lopa, C. Recordati, Giuseppe Talo', C. Turrisi, Marta Bottagisio, M. Losa, E. Scanziani, M. Moretti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalCalcified Tissue International
Publication statusAccepted/In press - Apr 13 2016


  • Bone graft
  • Dynamic culture
  • Femur
  • Mesenchymal stem cells
  • Ovine model
  • Tibia

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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