title: Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair.
abstract: One of the biggest challenges in regenerative medicine is promoting sufficient vascularisation of tissue-engineered constructs. One approach to overcome this challenge is to target the cellular hypoxia inducible factor (HIF-1α) pathway, which responds to low oxygen concentration (hypoxia) and results in the activation of numerous pro-angiogenic genes including vascular endothelial growth factor (VEGF). Cobalt ions are known to mimic hypoxia by artificially stabilising the HIF-1α transcription factor. Here, resorbable bioactive glass particles (38 μm and 100 μm) with cobalt ions incorporated into the glass network were used to create bioactive glass/collagen-glycosaminoglycan scaffolds optimised for bone tissue engineering. Inclusion of the bioactive glass improved the compressive modulus of the resulting composite scaffolds while maintaining high degrees of porosity (>97%). Moreover, in vitro analysis demonstrated that the incorporation of cobalt bioactive glass with a mean particle size of 100 μm significantly enhanced the production and expression of VEGF in endothelial cells, and cobalt bioactive glass/collagen-glycosaminoglycan scaffold conditioned media also promoted enhanced tubule formation. Furthermore, our results prove the ability of these scaffolds to support osteoblast cell proliferation and osteogenesis in all bioactive glass/collagen-glycosaminoglycan scaffolds irrespective of the particle size. In summary, we have developed a hypoxia-mimicking tissue-engineered scaffold with pro-angiogenic and pro-osteogenic capabilities that may encourage bone tissue regeneration and overcome the problem of inadequate vascularisation of grafts commonly seen in the field of tissue engineering.
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Trinity Centre for Bioengineering, Department of Mechanical Engineering, Trinity College, Dublin 2, Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), RCSI & TCD, Dublin 2, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinlan
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Trinity Centre for Bioengineering, Department of Mechanical Engineering, Trinity College, Dublin 2, Ireland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Partap
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, UK; Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Azevedo
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, UK; Division of Surgery & Interventional Science, University College London, London NW3 2QG, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Jell
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, UK; Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Trinity Centre for Bioengineering, Department of Mechanical Engineering, Trinity College, Dublin 2, Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), RCSI & TCD, Dublin 2, Ireland. Electronic address: fjobrien@rcsi.ie.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D001861:Bone Regeneration; D001842:Bone and Bones / Q000473:pathology; D002478:Cells, Cultured; D003035:Cobalt / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry*; D005898:Glass / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007477:Ions; D018919:Neovascularization, Physiologic; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D010100:Oxygen / Q000737:chemistry; D016062:Porosity; D044968:Regenerative Medicine / Q000379:methods; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D006025:Glycosaminoglycans; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007477:Ions; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D003094:Collagen; D010100:Oxygen
keywords: Angiogenesis; Bioactive glass; Cobalt; Collagen; Regenerative medicine; Scaffold