title: Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels.
abstract: Rapid and controlled vascularization within biomaterials is essential for many applications in regenerative medicine. The extent of vascularization is influenced by a number of factors, including scaffold architecture. While properties such as pore size and total porosity have been studied extensively, the importance of controlling the interconnectivity of pores has received less attention. A sintering method was used to generate hydrogel scaffolds with controlled pore interconnectivity. Poly(methyl methacrylate) microspheres were used as a sacrificial agent to generate porous poly(ethylene glycol) diacrylate hydrogels with interconnectivity varying based on microsphere sintering conditions. Interconnectivity levels increased with sintering time and temperature with resultant hydrogel structure showing agreement with template structure. Porous hydrogels with a narrow pore size distribution (130-150 μm) and varying interconnectivity were investigated for their ability to influence vascularization in response to gradients of platelet-derived growth factor-BB (PDGF-BB). A rodent subcutaneous model was used to evaluate vascularized tissue formation in the hydrogels in vivo. Vascularized tissue invasion varied with interconnectivity. At week 3, higher interconnectivity hydrogels had completely vascularized with twice as much invasion. Interconnectivity also influenced PDGF-BB transport within the scaffolds. An agent-based model was used to explore the relative roles of steric and transport effects on the observed results. In conclusion, a technique for the preparation of hydrogels with controlled pore interconnectivity has been developed and evaluated. This method has been used to show that pore interconnectivity can independently influence vascularization of biomaterials.
authors.affiliation: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Service, Hines Veterans Administration Hospital , Hines, Illinois.
authors.forename: Sami I
authors.initials: SI
authors.lastname: Somo
authors.affiliation: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Service, Hines Veterans Administration Hospital , Hines, Illinois.
authors.forename: Banu
authors.initials: B
authors.lastname: Akar
authors.affiliation: 3 Department of Chemical and Biological Engineering, Illinois Institute of Technology , Chicago, Illinois.
authors.forename: Elif S
authors.initials: ES
authors.lastname: Bayrak
authors.affiliation: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Service, Hines Veterans Administration Hospital , Hines, Illinois.
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Larson
authors.affiliation: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Service, Hines Veterans Administration Hospital , Hines, Illinois.
authors.forename: Alyssa A
authors.initials: AA
authors.lastname: Appel
authors.affiliation: 3 Department of Chemical and Biological Engineering, Illinois Institute of Technology , Chicago, Illinois.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Mehdizadeh
authors.affiliation: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|3 Department of Chemical and Biological Engineering, Illinois Institute of Technology , Chicago, Illinois.
authors.forename: Ali
authors.initials: A
authors.lastname: Cinar
authors.affiliation: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Service, Hines Veterans Administration Hospital , Hines, Illinois.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brey
mesh_terms: D000818:Animals; D000077214:Becaplermin; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000737:chemistry; D016062:Porosity; D020574:Proto-Oncogene Proteins c-sis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D011092:Polyethylene Glycols; D019904:Polymethyl Methacrylate