Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen

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Abstract
Low immunogenicity and high repopulation capacity are crucial determinants for the functional and structural performance of acellular cardiovascular implants. The present study evaluates a detergent‐free, non‐proteolytic, actin‐disassembling regimen (BIO) for decellularization of heart valve and vessel grafts, particularly focusing on their bio‐functionality. Rat aortic conduits (rAoC; n = 89) and porcine aortic valve samples (n = 106) are decellularized using detergents (group DET) or the BIO regimen. BIO decellularization results in effective elimination of cellular proteins and significantly improves removal of DNA as compared with group DET, while the extracellular matrix (ECM) structure as well as mechanical properties are preserved. The architecture of rAoC in group BIO allows for improved bio‐functionalization with fibronectin (FN) in a standardized rat implantation model: BIO treatment significantly increases speed and amount of autologous medial cellular repopulation in vivo (p < 0.001) and decreases the formation of hyperplastic intima (p < 0.001) as compared with FN‐coated DET‐decellularized grafts. Moreover, there are no signs of infiltration with inflammatory cells. The present biological, detergent‐free, non‐proteolytic regimen balances effective decellularization and ECM preservation in cardiovascular grafts, and provides optimized bio‐functionality. Additionally, this study implies that the actin‐disassembling regimen may be a promising approach for bioengineering of acellular scaffolds from other muscular tissues, as for example myocardium or intestine. Copyright © 2017 John Wiley & Sons, Ltd.

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