title: Cardiac extracellular matrix-fibrin hybrid scaffolds with tunable properties for cardiovascular tissue engineering.
abstract: Solubilized cardiac extracellular matrix (ECM) is being developed as an injectable therapeutic that offers promise for promoting cardiac repair. However, the ECM alone forms a hydrogel that is very soft compared to the native myocardium. As both the stiffness and composition of the ECM are important in regulating cell behavior and can have complex synergistic effects, we sought to develop an ECM-based scaffold with tunable biochemical and mechanical properties. We used solubilized rat cardiac ECM from two developmental stages (neonatal, adult) combined with fibrin hydrogels that were cross-linked with transglutaminase. We show that ECM was retained within the gels and that the Young's modulus could be tuned to span the range of the developing and mature heart. C-kit+ cardiovascular progenitor cells from pediatric patients with congenital heart defects were seeded into the hybrid gels. Both the elastic modulus and composition of the scaffolds impacted the expression of endothelial and smooth muscle cell genes. Furthermore, we demonstrate that the hybrid gels are injectable, and thus have potential for minimally invasive therapies. ECM-fibrin hybrid scaffolds offer new opportunities for exploiting the effects of both composition and mechanical properties in directing cell behavior for tissue engineering.
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.
authors.forename: Corin
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Budina
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Stoppel
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Sullivan
authors.affiliation: Department of Cardiac Surgery, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Emani
authors.affiliation: Department of Cardiac Surgery, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Sitaram M
authors.initials: SM
authors.lastname: Emani
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA; Cellular, Molecular and Developmental Biology Program, Sackler School for Graduate Biomedical Sciences, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA. Electronic address: lauren.black@tufts.edu.
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Black
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D005782:Gels / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007267:Injections; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005782:Gels; D005337:Fibrin; D019009:Proto-Oncogene Proteins c-kit
keywords: Biomimetic material; Cardiac tissue engineering; Extracellular matrix; Fibrin; Mechanical properties