title: Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications.
abstract: Here, we describe a porous 3-dimensional collagen scaffold material that supports capillary formation in vitro, and promotes vascularization when implanted in vivo. Collagen scaffolds were synthesized from type I bovine collagen and have a uniform pore size of 80 μm. In vitro, scaffolds seeded with primary human microvascular endothelial cells suspended in human fibrin gel formed CD31 positive capillary-like structures with clear lumens. In vivo, after subcutaneous implantation in mice, cell-free collagen scaffolds were vascularized by host neovessels, whilst a gradual degradation of the scaffold material occurred over 8 weeks. Collagen scaffolds, impregnated with human fibrinogen gel, were implanted subcutaneously inside a chamber enclosing the femoral vessels in rats. Angiogenic sprouts from the femoral vessels invaded throughout the scaffolds and these degraded completely after 4 weeks. Vascular volume of the resulting constructs was greater than the vascular volume of constructs from chambers implanted with fibrinogen gel alone (42.7±5.0 μL in collagen scaffold vs 22.5±2.3 μL in fibrinogen gel alone; p<0.05, n = 7). In the same model, collagen scaffolds seeded with human adipose-derived stem cells (ASCs) produced greater increases in vascular volume than did cell-free collagen scaffolds (42.9±4.0 μL in collagen scaffold with human ASCs vs 25.7±1.9 μL in collagen scaffold alone; p<0.05, n = 4). In summary, these collagen scaffolds are biocompatible and could be used to grow more robust vascularized tissue engineering grafts with improved the survival of implanted cells. Such scaffolds could also be used as an assay model for studies on angiogenesis, 3-dimensional cell culture, and delivery of growth factors and cells in vivo.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.|Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia.
authors.forename: Elsa C
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Department of Biomedical Engineering, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Shyh-Ming
authors.initials: SM
authors.lastname: Kuo
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Kong
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.|Department of Surgery, University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.|Faculty of Health Sciences, Australian Catholic University, Fitzroy, Victoria, Australia.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Morrison
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.|Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia.|O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.|Department of Surgery, University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.|Faculty of Health Sciences, Australian Catholic University, Fitzroy, Victoria, Australia.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Mitchell
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.|Department of Surgery, University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Shiang Y
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.|Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia.
authors.forename: Guei-Sheung
authors.initials: GS
authors.lastname: Liu
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology*; D005340:Fibrinogen; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005340:Fibrinogen; D003094:Collagen