3D Printed Pericardium Hydrogels To Promote Wound Healing in Vascular Applications

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 oversimplify 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, which resulted in scaffolds with stiffness between 0.5 and 20 kPa. The formed hybrid hydrogel was confirmed through a reduction in primary amines post-cross-linking. 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 < 0.05) lower with hybrid hydrogels compared to single component PEG or HPM hydrogels. This reduction in inflammatory cytokines could impact the healing environment that persists at the implantation site. Finally, using this developed hybrid hydrogel, models of neonatal vasculature were manufactured using digital light projection (DLP) 3D printing. The structural control achieved with this novel biomaterial suggests a promising new tool in vascular graft development and research, with potential for complex structures for use in congenital heart defect reconstruction.

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“…Protein was isolated following the methods explained above with Halt Protease Inhibitor (ThermoFisher, Waltham, MA) added to RIPA, including a 1:100 FBS:RIPA control. Mini‐Protean TGX (Bio‐Rad, Hercules, CA) gels were loaded with Laemmli buffer and samples, as described . Gels were run for 45 min at 120 V in 1× Tris‐Glycine buffer and fixed in 5% acetic acid, 45% deionized distilled water (ddH 2 O, >18.2 MΩ resistivity), and 50% methanol for 30 min.…”

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“…The 3D-printed hybrid scaffold based on poly(ethylene glycol) (PEG) and homogenized pericardium matrix was developed in order to promote wound healing in vascular grafts that can support the replacement of injured vessel wound after surgical reconstruction ( 70 ). The incorporation of homogenized pericardium into PEG matrix affects the modulus of the scaffold as well as reduces the inflammatory signal of macrophages.…”