Abstract
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.
Highlights
Due to the ageing of human populations, the number of elderly patients suffering from chronic diseases or end-stage organ failure is constantly increasing
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
The host response to these materials can depend on several aspects such as the original species, the tissue from which the extracellular matrix (ECM) has been isolated, the mechanical loading, the onset of biologic reaction and the effects of trophic factors to which the scaffold is exposed following implantation and host blood perfusion
Summary
Due to the ageing of human populations, the number of elderly patients suffering from chronic diseases or end-stage organ failure is constantly increasing. The request for organ and tissue (heart, kidney, lung, pancreas, cardiac valves, cartilage, etc...) far exceeds the number of available donors (Table 1). Tissue substitutes have demonstrated a limited durability (heart valve substitutes, ligament and tendons, cartilage) and artificial prosthetic devices may badly affect patient’s quality of life (VADS, pacemaker, hemo-dialysis, etc.). The host response to these materials can depend on several aspects such as the original species (e.g. porcine, equine, bovine, fish), the tissue from which the extracellular matrix (ECM) has been isolated (e.g., dermis, small intestine, pericardium, cornea), the mechanical loading, the onset of biologic reaction and the effects of trophic factors to which the scaffold is exposed following implantation and host blood perfusion. Tissue treatment and decontamination/sterilization methods applied during manufacturing process can markedly affect remodelling and functional outcome
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