Engineering Mineralized and Load Bearing Tissues

Abstract

Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio- temporal gradients in oxygen, nutrients and accumulation of waste prod- ucts inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defi ned vascu- lature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper- porous scaffolds have been proposed to address this problem with reason- able success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of bio- manufacturing techniques, such as soft- and photo-lithography or 3D bio- printing, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chap- ter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We fi rst review the development of func- tional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascu- larized scaffolds for bone tissue engineering.