title: Recapitulating endochondral ossification: a promising route to in vivo bone regeneration.
abstract: Despite its natural healing potential, bone is unable to regenerate sufficient tissue within critical-sized defects, resulting in a non-union of bone ends. As a consequence, interventions are required to replace missing, damaged or diseased bone. Bone grafts have been widely employed for the repair of such critical-sized defects. However, the well-documented drawbacks associated with autografts, allografts and xenografts have motivated the development of alternative treatment options. Traditional tissue engineering strategies have typically attempted to direct in vitro bone-like matrix formation within scaffolds prior to implantation into bone defects, mimicking the embryological process of intramembranous ossification (IMO). Tissue-engineered constructs developed using this approach often fail once implanted, due to poor perfusion, leading to avascular necrosis and core degradation. As a result of such drawbacks, an alternative tissue engineering strategy, based on endochondral ossification (ECO), has begun to emerge, involving the use of in vitro tissue-engineered cartilage as a transient biomimetic template to facilitate bone formation within large defects. This is driven by the hypothesis that hypertrophic chondrocytes can secrete angiogenic and osteogenic factors, which play pivotal roles in both the vascularization of constructs in vivo and the deposition of a mineralized extracellular matrix, with resulting bone deposition. In this context, this review focuses on current strategies taken to recapitulate ECO, using a range of distinct cells, biomaterials and biochemical stimuli, in order to facilitate in vivo bone formation.
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.|Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.
authors.forename: Emmet M
authors.initials: EM
authors.lastname: Thompson
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.|Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.
authors.forename: Amos
authors.initials: A
authors.lastname: Matsiko
authors.affiliation: Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Centre Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Farrell
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.|Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Ireland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.|Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001861:Bone Regeneration; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D019902:Chondrocytes / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009389:Neovascularization, Pathologic; D010012:Osteogenesis / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials
keywords: bone; developmental engineering; endochondral ossification; hypertrophy; intramembranous ossification; mesenchymal stem cells