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3D Printed Pericardium Hydrogels to Promote Wound Healing in Vascular Applications Laura G. Bracaglia, Michael J Messina, Shira Winston, Che-Ying Kuo, Max Lerman, and John P Fisher Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.7b01165 • Publication Date (Web): 04 Oct 2017 Downloaded from http://pubs.acs.org on October 5, 2017
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Biomacromolecules
3D Printed Pericardium Hydrogels to Promote Wound Healing in Vascular Applications Laura G. Bracaglia1, Michael Messina1, Shira Winston1, Che-Ying Kuo1, 2, Max Lerman1., 3, 4, John P. Fisher1*
1. Fischell Department of Bioengineering, University of Maryland, College Park, MD 2. Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System 3. Surface and Trace Chemical Analysis Group, Material Measurement Laboratory, National Institutes of Standards and Technology, Gaithersburg, MD 4. Department of Materials Science, University of Maryland, College Park, MD Keywords:
ECM hydrogel scaffold, 3D Printed Hydrogel, Vascular wound healing, vascular
hydrogel scaffold, pericardium, inflammation *Corresponding Author:
John P. Fisher
Fischell Family Distinguished Professor & Department Chair Fischell Department of Bioengineering University of Maryland
ACS Paragon Plus Environment
Biomacromolecules
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3238 Jeong H. Kim Engineering Building College Park, Maryland 20742 Work: 301 405 8782 Fax:
301 314 6868
Email:
[email protected] ACS Paragon Plus Environment
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Biomacromolecules
Abstract
Vascular grafts that can support total replacement and maintenance by the body of the injured vessel would improve outcomes of major surgical reconstructions. Building scaffolds using components of the native vessel can encourage biological recognition by native cells as well as mimic mechanical characteristics of the native vessel. Evidence is emerging that incorporating predetermined building-blocks into a tissue engineering scaffold may over simplify the environment, and ignore critical structures and binding sites essential to development at the implant. We propose the development of a 3D-printable and degradable hybrid scaffold by combining polyethylene glycol (PEG)acrylate and homogenized pericardium matrix (HPM) to achieve appropriate biological environment as well as structural support. It was hypothesized that incorporation of HPM into PEG hydrogels would affect modulus of the scaffold, and that the modulus and biological component would reduce the inflammatory signals produced from arriving macrophages and nearby endothelial cells. HPM was found to provide a number of tissue specific structural proteins including collagen, fibronectin, and glycosaminoglycans. HPM and PEGacrylate formed a hybrid hydrogel with significantly distinct modulus depending on concentration of either component, resulting in scaffolds with stiffness between 0.5 and 20 kPa. The formed hybrid hydrogel was confirmed through a reduction in primary amines postcrosslinking. Using these hybrid scaffolds, rat bone marrow derived macrophages developed an M2 phenotype in response to low amounts (0.03%, w/v) of HPM in culture, but responded with inflammatory phenotypes to high concentrations (0.3%, w/v). When cultured together with endothelial cells, both M1 and M2 macrophages were detected, along with a combination of both inflammatory and healing cytokines. However, the expression of inflammatory cytokines TNFα and IL1β was significantly (p
