title: Incorporation of fibrin into a collagen-glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction.
abstract: Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with a collagen-glycosaminoglycan backbone structure. Human vascular smooth muscle cells (vSMCs) were successfully incorporated into the FCG scaffold and demonstrated excellent viability over 7 days, while proliferation of these cells also increased significantly. VSMCs were seeded into both FCG and fibrin-only gels at the same seeding density for 7 days and while FCG scaffolds did not demonstrate a reduction in size, fibrin-only gels contracted to 10% of their original diameter. The FCG scaffold, which is composed of natural biomaterials, shows potential for use in applications where dimensional stability is crucial to the functionality of the tissue.
  
  
  CONCLUSIONS
  Fibrin is a versatile scaffold for tissue engineering applications, but its weak mechanical properties leave it susceptible to cell-mediated contraction, meaning the dimensions of the fibrin construct will change over time. We have reinforced fibrin with a collagen glycosaminoglycan matrix and characterised the mechanical properties and bioactivity of the reinforced fibrin (FCG). This is the first scaffold manufactured from all naturally derived materials that resists cell-mediated contraction. In fact, over 7 days, the FCG scaffold fully resisted cell-mediated contraction of vascular smooth muscle cells. This FCG scaffold has many potential applications where natural scaffold materials can encourage regeneration.
authors: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; School of Mechanical and Design Engineering, Dublin Institute of Technology, Bolton St, Dublin 1, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.
authors: Claire M
authors: CM
authors: Brougham
authors: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.
authors: Tanya J
authors: TJ
authors: Levingstone
authors: AME-Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany.
authors: Stefan
authors: S
authors: Jockenhoevel
authors: School of Medicine & Medical Science, University College Dublin, Dublin 4, Ireland.
authors: Thomas C
authors: TC
authors: Flanagan
authors: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland. Electronic address: fjobrien@rcsi.ie.
authors: Fergal J
authors: FJ
authors: O'Brien
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D019245:Compressive Strength; D055119:Elastic Modulus; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005109:Extracellular Matrix / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D009119:Muscle Contraction / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds
chemical_list: D006025:Glycosaminoglycans; D005337:Fibrin; D003094:Collagen
keywords: Cardiovascular scaffold; Fibrin; Heart valve; Tissue engineering