Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells

Collagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate the use of these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model. Cell-seeded constructs were pre-treated with either control or osteogenic media. Cell-free and collagen-only groups were included, as was a clinically approved bone void filler as a control for the material. After 8 weeks implantation, cell-free collagen-HA scaffolds and those that were pre-seeded with osteogenically differentiated hASCs supported bone formation and vascular invasion at comparable rates. HA-reinforcement allowed collagen constructs to maintain their implanted shape, provided for improved cell-tissue-scaffold integration, and resulted in a more organized tissue when pre-treated in an osteogenic induction medium. Scaffold type and pre-treatment also determined osteoclast activity and therefore potential remodeling of the constructs. Results suggest that it may be necessary to match the scaffold with a particular cell type and cell-specific pre-treatment to achieve optimal bone formation.