Dual functional approaches for osteogenesis coupled angiogenesis in bone tissue engineering

Bone fracture healing is a multistep and overlapping process of inflammation, angiogenesis and osteogenesis. It is initiated by inflammation, causing the release of various cytokines and growth factors. It leads to the recruitment of stem cells and formation of vasculature resulting in the functional bone formation. This combined phenomenon is used by bone tissue engineers from past few years to address the problem of vasculature and osteogenic differentiation during bone regeneration. In this review, we have discussed all major studies reporting the dual functioning approach to promote osteogenesis coupled angiogenesis using various scaffolds. These scaffolds are broadly classified into four types based on the nature of their structural and functional components. The functionality of the scaffold is either due to the structural components or the loaded cargo which conducts or induces the coupled functionality. Dual delivery system for osteoinductive and angioinductive factors ensures the co-delivery of two different types of molecules to induce osteogenesis and angiogenesis. Single delivery scaffold for angioinductive and osteoinductive molecule releases single type of molecules which could induce both angiogenesis and osteogenesis. Osteoconductive scaffold consisted of bone constituents releases angioinductive factors. Osteoconductive and angioconductive scaffold composed of components which provide the native substrate features for osteogenesis and angiogenesis. This review article also discusses the studies highlighting the synergism of physico-chemical stimuli as dual functioning feature to enhance angiogenesis and osteogenesis simultaneously. In addition, this article covers one of the least discussed area of the bone regeneration i.e. 'cartilage formation as a median between angiogenesis and osteogenesis'.