Early failure of xenogenous de-cellularised pulmonary valve conduits — a word of caution!☆

Rüffer, André; Purbojo, Ariawan; Cicha, Iwona; Glöckler, Martin; Potapov, Sergej; Dittrich, Sven; Cesnjevar, Robert

doi:10.1016/j.ejcts.2010.01.044

Cited by 98 publications

(73 citation statements)

References 24 publications

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“…Currently available acellular xenogeneic pulmonary heart valve scaffolds have shown clinical outcomes [17][18][19][20] that have indicated the need for the development of acellular valved conduits that are devoid of cells, DNA and residual a-gal. To the authors' knowledge, this is the first study that has assessed the total DNA and the presence of a-gal in all regions (leaflets, pulmonary wall, myocardium, and leaflet connection) of an acellular porcine pulmonary root conduit.…”

Section: Figmentioning

confidence: 99%

“…A number of other studies later reported inflammatory responses to the Matrix PÔ porcine pulmonary grafts associated with peripheral conduit narrowing. 17,19 It was also reported that the Matrix PÔ Plus valve displayed early obstruction following implantation in pediatric patients. 20 It is likely that these problems were due to the glutaraldehyde fixed pericardial patches used in the grafts.…”

mentioning

confidence: 99%

“…The Matrix P porcine pulmonary valve (AutoTissue) comprised an acellular porcine pulmonary valve supported by a glutaraldehydefixed equine pericardial patch. 17 Konertz et al 18 reported on the intermediate-term clinical performance of Matrix PÔ (n = 9) and Matrix PÔ Plus (n = 52) implantation. The grafts were favorable compared to other currently available implants.…”

mentioning

confidence: 99%

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Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

Luo

Korossis

Wilshaw

et al. 2014

Tissue Engineering Part A

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Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g., during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with hypotonic Tris buffer (HTB; 10 mM Tris pH 8.0, 0.1% (w/v) EDTA, and 10 KIU aprotinin), 0.1% (w/v) sodium dodecyl sulfate in HTB, two cycles of DNase and RNase, and sterilization with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extracellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96% throughout all regions of the acellular tissue and no functional genes were detected using polymerase chain reaction. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic, and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labeling and antibody absorption assay confirmed a lack of a-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular outflow tract reconstruction e.g., during the Ross procedure.

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Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

Luo

Korossis

Wilshaw

et al. 2014

Tissue Engineering Part A

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“…It has also been described for use in repair of rotator cuff defects [59,60], as well as for the treatment of diabetic foot ulcers [61]. Finally patch of EP tissue were applied either for the coverage [17] or for the self-made manufacture of heart valves substitutes [62]. Like many of the xenogeneic tissues intended for clinical use, even the EP patches are supplied after GLU fixation.…”

Section: Equine Pericardiummentioning

confidence: 99%

“…Scaffolds derived from mammalian tissues have been used to repair or replace a variety of damaged or diseased tissues including cardiac [1,2], esophageal [3,4], dermal [5], musculotendinous [6,7] and ocular [8], among others. Results of preclinical and clinical studies have varied from success [9][10][11] to complete failure [12][13][14][15][16][17]. The host response to these materials can depend on several aspects such as the original species (e.g.…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility Evaluation Criteria for Novel Xenograft Materials: Distribution and Quantification of Remnant Nucleic Acid and Alpha-Gal Epitope

Naso¹,

Andrea²,

Iop³

2013

J Stem Cell Res Ther

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Objective: Commercially decellularized xenogeneic scaffolds are currently employed as for the healing of diseased tissues. Strangely enough their use is permitted even in absence of any assessment of the elimination of xenogeneic cell material, as the alpha-Gal epitopes. In addition, the decellularization procedures are not monitored to prove the elimination of the calcific potential associated to the nucleic acids remnants. The currently treatment with glutaraldehyde is unable to grant a complete immuno-tolerance of implanted xenogeneic tissues, reducing but not eliminating the immunogenicity particularly for the alpha-Gal epitope (the major hindrance for the success of xenotransplantation). Recently, our group has extensively reported studies focused on the evaluation of biocompatibility properties of xenogeneic tissues. In this report we are performing this investigation and nucleic acid detection to novel xenogeneic tissues that have shown very promising preclinical/clinical results in different areas of application. Methods:The alpha-Gal quantification was conducted by an ELISA test previously developed and patented by our research team which involves the use of the monoclonal anti apha-Gal antibody M86. Immunofluorescence analysis was performed for the visual distribution of both xenogeneic epitopes and nucleic acids residues. Finally for the total DNA quantification a commercially available kit was adopted.Results: While the amount and distribution of the alpha-Gal epitopes was found different between the investigated biomaterials, the presence of nucleic acid remnants has been revealed as common feature, even in those tissues delivered as acellular by the manufacturer. Conclusion:Insufficient quantitative evaluations performed at preclinical level about the residual content of xenogeneic epitopes, detergents and nucleic acid materials in scaffolds have led to disappointing and disastrous results. The risk of these dramatic accidents reoccurring remains very high unless safety parameters, among which the complete removal of major xenogeneic determinants (alpha-Gal) and calcification-prone nucleic acid residues, are identified and introduced in manufacturing practices.

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Xenogeneic Serum‐Free Human Cell‐Derived Tissue Engineered Matrices for the Development of Clinical‐Grade Biomimetic Cardiovascular Devices

Zaytseva

Visser

Ehterami

et al. 2023

Advanced Therapeutics

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The development of next‐generation biomimetic cardiovascular implants using tissue engineering concepts can address the existing shortcomings of the clinically available prostheses, offering the possibility to generate life‐long, native‐analogous constructs with self‐remodeling and regenerative capacities. Scaffolds for tissue‐engineered cardiovascular prostheses can be obtained from allogenic cell sources, that can then produce human tissue‐engineered matrices (hTEMs) in vitro. Traditionally, fetal bovine serum (FBS) is used as a universal cell growth supplement. However, concerns regarding its biosafety remain a challenge for clinical translation. The aim of this study is to develop a novel xenogeneic serum‐free approach for the manufacturing of clinical grade hTEMs. To achieve this, decellularized hTEMs are generated under xenogeneic serum‐free conditions and have subsequently demonstrated hTEMs perform similarly to the FBS‐supplemented control group in terms of extracellular matrix (ECM) composition, hemocompatibility, thrombogenicity, and calcification potential. Finally, the xenogeneic serum‐free protocol is successfully adapted to the development of hTEM‐based tissue‐engineered heart valves for the systemic circulation, showing proof‐of‐concept functionality in vitro. Overall, the data suggest the effectiveness of xenogeneic serum‐free culture method as a valid alternative to FBS for the production of hTEM for cardiovascular applications.

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Early failure of xenogenous de-cellularised pulmonary valve conduits — a word of caution!☆

Cited by 98 publications

References 24 publications

Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

Biocompatibility Evaluation Criteria for Novel Xenograft Materials: Distribution and Quantification of Remnant Nucleic Acid and Alpha-Gal Epitope

Xenogeneic Serum‐Free Human Cell‐Derived Tissue Engineered Matrices for the Development of Clinical‐Grade Biomimetic Cardiovascular Devices

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