Enhanced Vascular Biocompatibility and Remodeling of Decellularized and Secured Xenogeneic/Allogeneic Matrices in a Porcine Model

Abstract

Background/Purpose: Calcifications and absence of growth potential are the major drawbacks of glutaraldehyde-treated prosthesis. Decellularized and secured xeno-/allogeneic matrices were assessed in a preclinical porcine model for biocompatibility and vascular remodeling in comparison to glutaraldehyde-fixed bovine pericardium (GBP; control). Methods: Native human (fascia lata, pericardium) and porcine tissues (peritoneum) were used and treated. In vitro, biopsies were performed before and after treatment to assess decellularization (hematoxylin and eosin/DAPI). In vivo, each decellularized and control tissue sample was implanted subcutaneously in 4 mini-pigs. In addition, 9 mini-pigs received a patch or a tubularized prosthesis interposition on the carotid artery or abdominal aorta of decellularized (D) human fascia lata (DHFL; n = 4), human pericardium (DHP; n = 9), porcine peritoneum (DPPt; n = 7), and control tissue (GBP: n = 3). Arteries were harvested after 1 month and subcutaneous samples after 15–30 days. Tissues were processed for hematoxylin and eosin/von Kossa staining and immunohistochemistry for CD31, alpha-smooth muscle actin, CD3, and CD68. Histomorphometry was achieved by point counting. Results: A 95% decellularization was confirmed for DHP and DPPt, and to a lower degree for DHFL. In the subcutaneous protocol, CD3 infiltration was significantly higher at day 30 in GBP and DHFL, and CD68 infiltration was significantly higher for GBP (p < 0.05). In intravascular study, no deaths, aneurysms, or pseudoaneurysms were observed. Inflammatory reaction was significantly higher for DHFL and GBP (p < 0.05), while it was lower and comparable for DHP/DPPt. DHP and DPPt showed deeper recellularization, and a new arterial wall was characterized. Conclusions: In a preclinical model, DPPt and DHP offered better results than conventional commercialized GBP for biocompatibility and vascular remodeling.

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

“…Human pericardial samples were obtained as discharge material from cadavers [149,150,151,152,153,154,155] or from consenting patients scheduled for cardiothoracic surgery [156,157,158,159]. Currently, various decellularization methods have been reported (Table 4), most of which are based on the use of detergent–enzymatic treatment [149,150,151,152,155,158,159]. Furthermore, recent studies successfully tested the SDS-based decellularization method [156] and a novel protocol based on the use of less traditional chemical agents (i.e., acetone and ethanol) [153,154,155].…”

“…Currently, various decellularization methods have been reported (Table 4), most of which are based on the use of detergent–enzymatic treatment [149,150,151,152,155,158,159]. Furthermore, recent studies successfully tested the SDS-based decellularization method [156] and a novel protocol based on the use of less traditional chemical agents (i.e., acetone and ethanol) [153,154,155]. All these processes showed a good decellularization rate and a complete removal of cell surface antigens, without affecting ECM structure.…”

“…Chemically decellularized pericardial patches were in vivo tested into animal models of arterial wall regeneration, being implanted as a vascular patch on the abdominal aorta of rats [153,154] or the carotid/aorta of Vietnamese pigs [155]. These intravascular studies highlighted enhanced graft integration, low immunogenicity, and recellularization of scaffolds.…”

“…In the clinical practice, decellularized aortic and pulmonary heart valve allografts have already received approval for surgical application and have been used for implant in patients with various valvular pathologies with satisfactory clinical outcomes [138,143,146,152,153,154,155] (Table 1). In particular, aortic valve allografts were succeffully tested for aortic root replacement in the presence of congenital or acquired aortic valve disease, aortic aneurysm with aortic valve disease, or native or prosthetic aortic valve endocarditis [59,63,66].…”

“…As it was demonstrated by many clinical cases and animal studies [293], the efficacy of amniotic membrane in promoting soft tissues healing and regeneration is due to its anti-inflammatory and immunological properties as well as to cytoprotective ability [120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,…”