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

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.

Influence of Laminin Coating on the Autologous In Vivo Recellularization of Decellularized Vascular Protheses

“…Aortic graft harvesting (n = 37) was conducted as recently published [6]. In brief, donor rats were euthanized by isoflurane.…”

“…Decellularization reduces the inflammatory response against non-autologous implants [5]. Depending on the agents that are used to obtain acellular scaffolds, the speed of cellular repopulation varies [6]. Implant coating with bioactive proteins can further accelerate the repopulation process [7,8,9].…”

Chemical cross‐linking of xenopericardial biomeshes: A bottom‐up study of structural and functional correlations

“…In this regard, biomesh must be compatible with the surrounding tissue, that is, be not cytotoxic or stiff and possess desirable topology and biodegradation rate . For example, for heart valve prostheses, smooth surface, proteolytic stability and mechanical strength are demanded, while resorbability and moderate roughness are beneficial to bone augmentation . The advantages of biological tissue‐derived materials over the synthetic analogues include their superior hemodynamic properties and avoidance of a chronic anticoagulant therapy.…”

Assessment of decellularization of heart bioimplants using a Raman spectroscopy method

“…Parts of this work, i.e., the peak values for GAG, amide I, and amide III structures, have been published in a previous article. 12…”

“…In addition, analysis of 2-D diagrams revealed that DET decellularization yields better preservation of GAGs in comparison with BIO decellularization, as recently reported. 12 On the other hand, during treatment of leaves by the protocol of DET decellularization, the amount of nucleic acids (DNA) is greater than in the samples subjected to BIO decellularization. Input optical coefficients enable a qualitative assessment of the protocols of DET and BIO decellularization in terms of the concentrations of GAG, proteins, amides, and DNA.…”