title: Engineering Pre-vascularized Scaffolds for Bone Regeneration.
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 products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature 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 reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, 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 chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional 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-vascularized scaffolds for bone tissue engineering.
authors.affiliation: Department of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, NSW, Australia.|Bioengineering Laboratory, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia.
authors.forename: Giada D G
authors.initials: GD
authors.lastname: Barabaschi
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, USA.
authors.forename: Vijayan
authors.initials: V
authors.lastname: Manoharan
authors.affiliation: Department of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, NSW, Australia.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Bioengineering Laboratory, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia. bertasso@ohsu.edu.|Center for Regenerative Medicine, Oregon Health and Science University, Portland, OR, USA. bertasso@ohsu.edu.|Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, Oregon Health and Science University, Portland, OR, USA. bertasso@ohsu.edu.
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Bertassoni
mesh_terms: D001672:Biocompatible Materials / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods* / Q000639:trends; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials
keywords: Angiogenesis; Bioprinting; Bone regeneration; Bone scaffolds; Microfabrication; Tissue engineering; Vascularization