Dye-Mediated Photo-Oxidation Biomaterial Fixation: Analysis of Bioinductivity and Mechanical Properties of Bovine Pericardium for Use in Cardiac Surgery.

Sean Kang,Karl T Wagner,Simranjit S Pattar,Paul W M Fedak,Kristina Jeon,Vishnu Vasanthan,Ali Fatehi Hassanabad,Guoqi Teng

doi:10.3390/ijms221910768

Abstract

Extracellular matrix bioscaffolds can influence the cardiac microenvironment and modulate endogenous cellular mechanisms. These materials can optimize cardiac surgery for repair and reconstruction. We investigated the biocompatibility and bioinductivity of bovine pericardium fixed via dye-mediated photo-oxidation on human cardiac fibroblast activity. We compared a dye-mediated photo-oxidation fixed bioscaffold to glutaraldehyde-fixed and non-fixed bioscaffolds reported in contemporary literature in cardiac surgery. Human cardiac fibroblasts from consenting patients were seeded on to bioscaffold materials to assess the biocompatibility and bioinductivity. Human cardiac fibroblast gene expression, secretome, morphology and viability were studied. Dye-mediated photo-oxidation fixed acellular bovine pericardium preserves human cardiac fibroblast phenotype and viability; and potentiates a pro-vasculogenic paracrine response. Material tensile properties were compared with biomechanical testing. Dye-mediated photo-oxidation fixed acellular bovine pericardium had higher compliance compared to glutaraldehyde-fixed bioscaffold in response to tensile force. The biocompatibility, bioinductivity, and biomechanical properties of dye-mediated photo-oxidation fixed bovine pericardium demonstrate its feasibility as a bioscaffold for use in cardiac surgery. As a fixed yet bioinductive solution, this bioscaffold demonstrates enhanced compliance and retains bioinductive properties that may leverage endogenous reparative pathways. Dye-mediated photo-oxidation fixed bioscaffold warrants further investigation as a viable tool for cardiac repair and reconstruction.

Highlights

Cardiac surgery is a heavily reconstructive specialty that relies on glutaraldehyde (GA) fixed bovine pericardium for robust and reproducible repair, in a variety of cases
RNA sequencing assessed if Dye-mediated photo-oxidation (DMPO)-fixed ECM could maintain healthy human cardiac fibroblast function when seeded on the bioscaffold
DMPO-fixed ECM induced higher human cardiac fibroblast transcription of angiogenin, fibroblast growth factor-1, and platelet-derived growth factor-D compared to GA-fixed ECM (Figure 1A)

Summary

Introduction

Cardiac surgery is a heavily reconstructive specialty that relies on glutaraldehyde (GA) fixed bovine pericardium for robust and reproducible repair, in a variety of cases. GA-fixed bovine pericardium is widely used because it is able to provide robust structural support and does not rapidly break down after implantation; but it is prone to calcification and inflammation, in addition to glutaraldehyde cytotoxicity [1,2,3,4,5,6]. Our group’s previous work explored non-fixed acellular porcine small intestinal submucosal extracellular matrix (SIS-ECM) and its ability to influence the local cardiac microenvironment. This material modulated cellular activity and enhanced endogenous mechanisms of repair by attenuating cardiac fibrosis, promoting angiogenesis and improving post-infarct cardiac function in small and large animal models [9,10,11]. Despite the benefits of non-fixed acellular bioscaffolds, challenges regarding resistance against breakdown, immunogenicity, and inflammation, seen in pediatric applications, remain hurdles to clinical translation [12,13,14]

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Conclusion