Strategies to direct vascularisation using mesoporous bioactive glass-based biomaterials for bone regeneration

Blood vessel formation, which encompasses sprouting of capillaries from pre-existing ones (angiogenesis) and the de novo assembly of endothelial progenitor cells to capillaries (vasculogenesis), is vital for biological processes such as organ development, tissue repair and regeneration, and wound healing. The biggest challenge in the regeneration of large bone defects remains the lack of adequate vascularisation within a scaffold/tissue construct to support cell viability and tissue growth. Thus, enhancing the angiogenic potential of biomaterial scaffolds after implantation is pivotal for the success of guided tissue regeneration. Bone is naturally a well vascularised tissue, therefore, for a bone substitute biomaterial to function, a vascular network within the scaffold is a prerequisite. Mesoporous bioactive glasses (MBG) have gained significant attention in the field of bone tissue engineering over the past decade due to their distinct structure and composition. While the ordered mesopores are too small for blood vessel ingrowth, mesopores can increase specific surface area, thus enhancing osteogenesis through controlled ion release and possibly angiogenesis by delivering pro-angiogenic drugs. Engineering the mesoporous structures is a prime example of applying nanotechnology to regenerative medicine. Large macro-pores can be incorporated into mesoporous glasses to produce a highly functional template for tissue regeneration. Various modification strategies for MBG scaffolds have been developed to stimulate angiogenesis, including the addition/delivery of inorganic ionic components, growth factors and drugs, manipulation of angiogenic growth factors such as fibroblast growth factor-1 and vascular endothelial growth factor, and mimicking hypoxic conditions. This review summarises the application of MBG-based biomaterials for bone regeneration with emphasis given to blood vessel formation.