title: The application of a thermoresponsive chitosan/β-GP gel to enhance cell repopulation of decellularized vascular scaffolds.
abstract: Decellularized arterial scaffolds have achieved success in advancing towards clinical use for small diameter vascular graft applications. Issues remain with effectively cell seeding these scaffolds, which may result in slow remodeling in vivo and reduced patency rates. This study aims to efficiently bulk load decellularized arterial scaffolds with cells and/or growth factors to promote cell migration within the scaffold. A chitosan/β-glycerophosphate (β-GP) hydrogel was used as a delivery vehicle for scaffold repopulation with rat mesenchymal stem cells (rMSCs) and/or murine hepatocyte growth factor (HGF). The thermoresponsivity of the chitosan/β-GP HGF gel was determined by rheological analysis and the release of HGF by ELISA. The chitosan/β-GP gel was fully injectable with gelation at 30°C in ∼30 min and demonstrated sustained controlled HGF release up to 28 days. Encapsulation of rMSCs allowed for consistent efficient cell delivery within the scaffold. Directional migration toward the released HGF was demonstrated within the medial layer of the scaffold up to a distance of 3 mm. The gel/cell/growth factor combination demonstrates a means of accelerating scaffold repopulation, without costly excessive in vitro maturation times.
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin 2, Ireland.
authors.forename: William S
authors.initials: WS
authors.lastname: Sheridan
authors.forename: Orna B
authors.initials: OB
authors.lastname: Grant
authors.forename: Garry P
authors.initials: GP
authors.lastname: Duffy
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001158:Arteries; D001705:Bioprosthesis; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D005994:Glycerophosphates / Q000737:chemistry*; D017228:Hepatocyte Growth Factor / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005994:Glycerophosphates; C553307:HGF protein, mouse; D017228:Hepatocyte Growth Factor; D048271:Chitosan
keywords: cell migration; chitosan/β-GP; decellularization; mesenchymal stem cells; thermoresponsive gel; vascular scaffold repopulation