Synthetic polymer coatings diminish chronic inflammation risk in large ECM-based materials.

Degradable materials that can support cell infiltration and remodeling are the basis of tissue engineered approaches to vascular repair. In addition, to replace or close a large area of the vasculature, a patch material or scaffold must also withstand high pressure over time. Extracellular matrix-based (ECM-based) scaffolds offer a biological substrate with environmental cues that can support the formation of appropriate vascular tissue. However, scaffolds made from pure natural materials can degrade rapidly, resulting in reduced mechanical integrity of the implant and possible chronic inflammation in the site. A hybrid biomaterial, combining the matrix-dense tissue pericardium with a layer of the degradable polymer poly(propylene fumarate) (PPF), is suited to withstand rapid enzymatic degradation and control the presentation of an unaltered natural tissue matrix for remodeling activity. In this study, we show that the polymer reinforced hybrid supports cellular infiltration, but has fewer macrophages in the vicinity of the implant after 6 weeks in vivo than an untreated tissue control in both athymic and immunocompetent rat models. This result is supported by changes seen in other inflammatory cell populations. Based on significant differences in the inflammatory response to untreated pericardium and PPF-reinforced pericardium, we conclude that the polymer reinforcement layer can be used as a tool to leverage presentation of the ECM molecules in ECM-based scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 494-504, 2019.

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

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 IL1ß 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.