Decellularized Cryopreserved Allografts as Off-the-Shelf Allogeneic Alternative for Heart Valve Replacement: In Vitro Assessment Before Clinical Translation

Abstract

Cryopreserved allogeneic conduits are the elective biocompatible choice among currently available substitutes for surgical replacement in end-stage valvulopathy. However, degeneration occurs in 15 years in adults or faster in children, due to recipient's immunological reactions to donor's antigens. Here, human aortic valves were decellularized by TRICOL, based on Triton X-100 and sodium cholate, and submitted to standard cryopreservation (TRICOL-human aortic valves (hAVs)). Tissue samples were analyzed to study the effects of the combined procedure on original valve architecture and donor's cell removal. Residual amounts of nucleic acids, pathological microorganisms, and detergents were also investigated. TRICOL-hAVs proved to be efficaciously decellularized with removal of donor's cell components and preservation of valve scaffolding. Trivial traces of detergents, no cytotoxicity, and abrogated bioburden were documented. TRICOL-hAVs may represent off-the-shelf alternatives for both aortic and pulmonary valve replacements in pediatric and grown-up with congenital heart disease patients.

A Comprehensive Comparison of Bovine and Porcine Decellularized Pericardia: New Insights for Surgical Applications

“…To our knowledge, this work represents the first attempt to assess any tissue specificity in a comparison between bovine and porcine pericardia before and after detergent decellularization, i.e., TRICOL procedure. Previously, we reported its efficacy in the decellularization of porcine and human cardiovascular tissues [15,[36][37][38][39]. This study demonstrates that TRICOL is effective in cell extraction from both bovine and porcine pericardia, without any adverse effects on both species' ECMs.…”

“…Such information is of paramount importance in developing effective therapeutic strategies targeted for each surgical indication. A comprehensive comparison of the most clinically applied pericardial replacements, i.e., bovine and porcine ones, has been performed after submitting native tissues to TRICOL decellularization [15,[36][37][38][39][40], in order to verify whether decellularization exerts a differential effect on these tissues in terms of their histological, immunohistochemical, biochemical, and ultrastructural properties, as well as their denaturation, biomechanical, and cytocompatibility profiles.…”

A porcine xenograft‐derived bone scaffold is a biocompatible bone graft substitute: An assessment of cytocompatibility and the alpha‐Gal epitope

“…28 Ionic detergents such as sodium dodecyl sulfate, and sodium deoxycholate or non-ionic detergents, such as triton X-100 used in our decellularization protocol, also present cytotoxic risks but are easily reduced with successive water washes, as done in our methodology, to trace, non-cytotoxic levels. 57,58 PAA penetrates substrates quickly to kill pathogens by oxidative damage 32 and is a safer alternative to many chemicals because it spontaneously breaks down into acetic acid and hydrogen peroxide when dissolved in water. 25 Previous work has proven PAA's efficacy in the clearance of viral and bacterial pathogens from cancellous bone substrate.…”

The Rapidly Evolving Concept of Whole Heart Engineering

“…In allogeneic settings, human leukocyte antigens (HLAs) are known in transplantation medicine to induce immune responses towards the donor's implanted tissue (heart, cardiac valves, etc.) [ 102 ]. Indeed, nucleic acids might result in similar effects [ 46 , 48 , 103 ].…”