Cell-free and cell-based approaches for bone regeneration.

The clinical augmentation of bone currently involves the use of autogenous or allogeneic bone grafts and synthetic materials, all of which are associated with limitations. Research on the safe enhancement of bone formation concerns the potential value of scaffolds, stem cells, gene therapy, and chemical and mechanical signals. Optimal scaffolds are engineered to provide mechanical stability while supporting osteogenesis, osteoconduction and/or osteoinduction. Scaffold materials include natural or synthetic polymers, ceramics, and composites. The resorption, mechanical strength and efficacy of these materials can be manipulated through structural and chemical design parameters. Cell-seeded scaffolds contain stem cells or progenitor cells, such as culture-expanded marrow stromal cells and multipotent skeletal progenitor cells sourced from other tissues. Despite extensive evidence from proof-of-principle studies, bone tissue engineering has not translated to clinical practice. Much of the research involves in vitro and animal models that do not replicate potential clinical applications. Problem areas include cell sources and numbers, over-reliance on existing scaffold materials, optimum delivery of factors, control of transgene expression, vascularization, integration with host bone, and the capacity to form bone and marrow structures in vivo. Current thinking re-emphasizes the potential of biomimetic materials to stimulate, enhance, or control bone's innate regenerative capacity at the implantation site.