Fabrication of vascularized bone grafts of predetermined shape with hydroxyapatite-collagen gel beads and autogenous mesenchymal stem cell composites.

Background: Advances in tissue-engineering techniques have enabled new procedures to be developed for bone regeneration. In this study, for engineering of structural tissues with supporting vascular networks, the authors attempted to produce vascularized tissue-engineered bone grafts using cultured mesenchymal stem cells/hydroxyapatite/collagen gel bead composites and vascular bundle implantation.

Methods: Twenty-four New Zealand White rabbits underwent implantation of ringed polytetrafluoroethylene vascular grafts (1 x 3 cm) in the medial thigh with the femoral vascular bundle passing through. The polytetrafluoroethylene grafts were left unfilled (group A), filled with hydroxyapatite/collagen gel beads (group B), or filled with mesenchymal stem cells/hydroxyapatite/collagen gel bead composites (group C). At 4, 8, 12, and 16 weeks, the implants were removed and radiographic and histologic examinations were conducted.

Results: Radiographic analysis revealed that the area of radiopacity within the chamber was highest in group C. The average calcified densities of groups B and C were between 0.99 +/- 0.11 and 1.29 +/- 0.14. Histologically, there was fibroadipose tissue within the chamber in group A. New tissue had grown into the matrix of the chambers of groups B and C, and substitution of the biomaterials was seen. Newly formed fibrovascular networks and osteoids were simultaneously seen. Bone marrow was observed in the vascular graft of group C 6 months after implantation.

Conclusions: Tissue-engineered vascularized bone grafts of predetermined shape were created with mesenchymal stem cell/hydroxyapatite/collagen gel bead composites. The results of this study showed that successful in vivo engineering of vascularized tissue-engineered bone grafts is possible.