title: An in vitro investigation to assess procedure parameters for injecting therapeutic hydrogels into the myocardium.
abstract: Localized delivery of stem cells is potentially a promising therapeutic strategy for regenerating damaged myocardium. Many studies focus on limiting the biologic component of cell loss, but few address the contribution of mechanical factors. This study investigates optimal parameters for retaining the largest volume of cell loaded hydrogels post intramyocardial injection, without compromising cell viability. In vitro, hydrogel was injected into porcine hearts using various needle designs. Hydrogel retention and distribution pattern was then determined. The two most promising needles were then investigated to understand the effect of needle geometry on stem cell viability. The needle to best impact cell viability was then used to investigate the effect of differing hydrogels on retention and distribution. Three-dimensional experimental modeling revealed needles with smaller diameter's to have greater poloxamer 407 hydrogel retention. No difference in retention existed among various needle designs of similar gauge, despite differences in bolus geometries. When hMSC's, embedded in fibrin hydrogel, were injected through helical and 26G bevel needles no difference in the percent of live cells was seen at 48 h. However, the helical group had almost half the metabolic activity of the 26G bevel group at both time points, and had a significant decline in the percent of live cells from 24 to 48 h. Varying gel type resulted in significantly more alginate being retained in the tissue in comparison to fibrin or poloxamer hydrogels. In conclusion, mechanical properties of injected hydrogels, and the diameter of the needle used, highly influences the volume of hydrogel retained. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2618-2629, 2017.
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), TCD & RCSI, Dublin, Ireland.
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Curley
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), TCD & RCSI, Dublin, Ireland.
authors.forename: Eimear B
authors.initials: EB
authors.lastname: Dolan
authors.affiliation: Cellular and Molecular Imaging Core, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Brenton
authors.initials: B
authors.lastname: Cavanagh
authors.affiliation: Advanced Materials and BioEngineering Research Centre (AMBER), TCD & RCSI, Dublin, Ireland.|Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Janice
authors.initials: J
authors.lastname: O'Sullivan
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.|Advanced Materials and BioEngineering Research Centre (AMBER), TCD & RCSI, Dublin, Ireland.|Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Duffy
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), TCD & RCSI, Dublin, Ireland.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018914:Cells, Immobilized / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D064593:Heterografts; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009339:Needles; D013552:Swine
chemical_list: D020100:Hydrogels
keywords: cardiac injection; cell therapy; hydrogel; infarction; retention