title: A novel composite construct increases the vascularization potential of PEG hydrogels through the incorporation of large fibrin ribbons.
abstract: Developing a mechanism to vascularize tissue-engineered constructs is imperative for transplant function and integration, particularly when delivering hypoxia-sensitive tissues, such as pancreatic islets. Previous efforts have focused on bulk modifications of scaffold materials rendering the entire construct permissive to vessel penetration or the formation of a porous structure where vessels can infiltrate the empty spaces. Here, we describe a novel construct composed of large fibrin ribbons encapsulated within a poly(ethylene glycol) (PEG) hydrogel. The PEG/fibrin ribbon composite scaffold facilitates coculture of adhesive and nonadhesive cell types, thus providing closely neighboring environments with distinct material properties specific to the needs of two clinically relevant cell populations. This advantage is demonstrated here by the successful coculture of pancreatic islets in the PEG component and vessel-forming endothelial cells in entrapped fibrin ribbons. Transplanted endothelial cells can form anastomosies with host vasculature, suggesting that our cocultures may lead to more rapid scaffold vascularization. Additionally, we show that surface-seeded endothelial cells form multicellular projections that migrate into nonadhesive PEG hydrogels along permissive fibrin ribbons, further demonstrating composite construct vascularization potential. Distribution of large fibrin ribbons throughout PEG hydrogels provide a potential mechanism for vascularization of a well-established biomaterial without inherently changing its desirable properties.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Campus Box 424, Boulder, Colorado 80309, USA.
authors.forename: Mariah N
authors.initials: MN
authors.lastname: Mason
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Mahoney
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005337:Fibrin / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects; D051379:Mice; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols; D005337:Fibrin