Towards a Novel Patch Material for Cardiac Applications: Tissue-Specific Extracellular Matrix Introduces Essential Key Features to Decellularized Amniotic Membrane

Abstract

There is a growing need for scaffold material with tissue-specific bioactivity for use in regenerative medicine, tissue engineering, and for surgical repair of structural defects. We developed a novel composite biomaterial by processing human cardiac extracellular matrix (ECM) into a hydrogel and combining it with cell-free amniotic membrane via a dry-coating procedure. Cardiac biocompatibility and immunogenicity were tested in vitro using human cardiac fibroblasts, epicardial progenitor cells, murine HL-1 cells, and human immune cells derived from buffy coat. Processing of the ECM preserved important matrix proteins as demonstrated by mass spectrometry. ECM coating did not alter the mechanical characteristics of decellularized amniotic membrane but did cause a clear increase in adhesion capacity, cell proliferation and viability. Activated monocytes secreted less pro-inflammatory cytokines, and both macrophage polarization towards the pro-inflammatory M1 type and T cell proliferation were prevented. We conclude that the incorporation of human cardiac ECM hydrogel shifts and enhances the bioactivity of decellularized amniotic membrane, facilitating its use in future cardiac applications.

Collagen Fibrils Mechanically Contribute to Tissue Contraction in an In Vitro Wound Healing Scenario

“…[54] In brief, decellularized scaffolds were washed using Ammonium bicarbonate (25 × 10 −3 m; Sigma-Aldrich)/Acetonitril Uvasol (2% (v/v); Merck) in water and twice with ammonium bicarbonate (25 × 10 −3 m)/Acetonitril (50% (v/v)) in water at 37 °C. [54] In brief, decellularized scaffolds were washed using Ammonium bicarbonate (25 × 10 −3 m; Sigma-Aldrich)/Acetonitril Uvasol (2% (v/v); Merck) in water and twice with ammonium bicarbonate (25 × 10 −3 m)/Acetonitril (50% (v/v)) in water at 37 °C.…”

Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives

“…Human heart decellularization has been applied to whole organs [137,139,140,141] or cardiac muscle fragments [142] harvested from cadavers and unusable for clinical transplantation, as well as to tissue sections procured during surgical procedures (i.e., implantation of a mechanical assist device, heart transplantation, and resection of a subaortic outflow tract obstruction) [135,138,143,144,145,146,147,148]. Left ventricular biopsies derived from myocardial infarction patients were also processed [138].…”

Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

“…The high cECM content hydrogels induced formation of striated cTnI and expression of Cx43, although the effect may be due to the varying storage modulus of the low (8 Pa) and high (60 Pa) cECM scaffolds rather than the cECM composition. Instead of combining cECM with single ECM components, Becker et al dry coated cell‐free amniotic membrane with cECM, combining two complex natural materials . While the cECM coating did not change scaffold mechanical properties, CMs showed improved adhesion and survival on cECM coated substrates compared to pure amniotic membrane.…”