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Tissue Eng Part A. 2017 Oct;23(19-20):1181-1195. doi: 10.1089/ten.tea.2016.0474. Epub 2017 Jun 21.

Alpha-Gal Inactivated Heart Valve Bioprostheses Exhibit an Anti-Calcification Propensity Similar to Knockout Tissues<sup/>.

Author information

1
1 Biocompatibility Innovation, Medical Device Biocompatibility Laboratory , Padova, Italy .
2
2 Cardiac Surgery Unit, Royal Children's Hospital , Melbourne, Australia .
3
3 Department of Paediatrics, University of Melbourne , Melbourne, Australia .
4
4 Avantea, Laboratory of Reproductive Technology , Cremona, Italy .
5
5 Department of Veterinary Medical Sciences, University of Bologna , Bologna, Italy .
6
6 Fondazione Avantea , Cremona, Italy .

Abstract

BACKGROUND:

Glutaraldehyde (GLA) has been used to crosslink bioprosthetic heart valve (BHVs) tissues to enhance their stability, besides ensuring a satisfactory degree of immunological tolerance. Unfortunately, GLA fixation does not guarantee a complete tissue biocompatibility of BHVs in currently used devices. The interaction between preformed human anti-alpha-Gal antibody and alpha-Gal antigens promotes the calcification of GLA-treated alpha-Gal-positive tissue. Recently, an alarming correlation between the presence of the alpha-Gal epitope and a premature BHVs degeneracy was reported. This article presents the results of a novel treatment called FACTA, for the inactivation of the alpha-Gal epitopes in porcine aortic valve tissue and commercial BHVs.

METHODS:

Evaluation of the alpha-Gal epitope inactivation was performed through a patented ELISA test, confirmed by western blot, immunofluorescence, and immunohistochemical analyses. Investigations were also conducted to assess the in vitro propensity to trigger thrombosis, calcification, and worsening of FACTA-treated tissue. To explain the mechanism of action through which the FACTA treatment acts, a specific experimental model, based on the mass spectroscopy approach, was performed.

RESULTS:

The study confirms that GLA is able to ensure the inactivation of approximately half alpha-Gal epitopes originally present in both porcine aortic valve tissue and marketed BHVs. By subjecting tissues to the FACTA procedure, it was possible to obtain an alpha-Gal inactivation degree of about 95% alongside to a reduced propensity from 72.6% to 85.4% to the in vitro calcification for porcine aortic valve tissue and 80.5% for commercial treated BHVs. FACTA was effective in decreasing oxidative tissue damage and protecting collagen from degradation. Finally, FACTA could further mitigate or even abrogate the need for early anticoagulation therapies after BHV implantation.

CONCLUSION:

A novel treatment, called FACTA, is effective to produce biological tissues that are less susceptible to enzymatic and oxidative stress and structural degradation, calcification, and thrombus formation. FACTA-treated tissues display a clear improvement of their biocompatibility that is characterized by an almost complete inactivation of the alpha-Gal epitope. FACTA prevents the xenogeneic tissue antigens from reacting with the host immune system, ensuring an effective shield effect that makes the tissue surface less reactive and more biocompatible.

KEYWORDS:

bioprosthetic heart valves; calcification; oxidative injury; xenogeneic epitopes

PMID:
29053434
DOI:
10.1089/ten.tea.2016.0474
[Indexed for MEDLINE]

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