Photooxidation Cross‐Linked, Glutaraldehyde Cross‐Linked, or Enzyme and Hydrostatic Pressure Processed Decellularized Biomaterials for Cardiovascular Repair Do Not Affect Host Response in a Rat Right Ventricular Outflow Flow Tract Reconstruction ( RVOT ) Model

Cardiovascular diseases (CVDs) were responsible for approximately 19 million deaths in 2020, marking an increase of 18.7% since 2010. Biological decellularized patches are common therapeutic solutions for CVD such as cardiac and valve defects. The preparation of biomaterials for cardiac patches involves two main processing methods: glutaraldehyde or photooxidation cross-linking (fixation) and noncross-linked (nonfixation) processing. Despite the variety of products available in the market, cardiac patches still suffer from significant limitations, failing to adequately mimic the properties of biological tissue and restore its function. This study assesses the impact of different processing methodologies on the biological and biomechanical outcomes of three commercially available cardiac patches (CorPatch, CardioCel, PhotoFix) and one newly developed decellularized cardiac patch (Adeka) when implanted as right ventricular outflow tract (RVOT) repair material on a rat model. Four different patches for cardiovascular repair were selected based on their processing approaches and included: photooxidation crosslinked (PhotoFix), glutaraldehyde crosslinked (CardioCel), noncross-linked small intestine submucosa (CorPatch) or enzyme, and hydrostatic pressure (Adeka) processed decellularized biomaterials. Structure and function were characterized prior to implantation via thickness mapping, cross-section morphology, 2D surface topography, 3D volume microstructure, biaxial testing, uniaxial tensile testing, ball burst, and suture retention. Their host-biomaterials response was assessed in vivo using a relevant model for cardiovascular repair: a rat (RVOT) reconstruction with 8 and 16-week timepoints. Topological analysis showed that the crosslinked cardiac patches had a more homogeneous thickness distribution when compared to the noncrosslinked patches. This agreed with histological evaluation, where cross-linking processed materials better preserved collagen content than noncrosslinked patches who were also more delaminated. Biaxial data demonstrated that all patches, except CorPatch, recapitulated the anisotropic behavior of healthy left ventricle tissue. The Adeka patch in-plane mechanics at 16 weeks was the one who better resembled the mechanics of healthy cardiac tissue. All patches showed appropriate biocompatibility and function at 8- and 16-week timepoints for RVOT patching. This included echocardiographic assessment, biomechanics, macrophage infiltration and polarization, and angiogenesis. Consistently with a more porous laminae structure, explants histology showed higher cell infiltration in non-crosslinked Adeka when compared to the crosslinked PhotoFix. Overall, both in vitro and in vivo tests indicate that the material processing does not impact the function, biomechanical performance, and the host response of the patches that can be considered as equally effective as materials based cardiac repair solutions.