Pericardial patches are the main representative of the most used implantable medical devices in the cardiovascular field. Autologous, allogeneic, and xenogeneic are the mainly exploited sources for pericardial harvesting to repair, regenerate, and replace damaged or harmed cardiovascular anatomical structures. Among the others, the bovine pericardium is the most used xenogeneic tissue in surgical practice. It has been widely employed for cardiovascular applications, such as endarterectomies, arterial closure, and bioprosthetic valve production due to its numerous advantages. Despite its extensive application, it inherently possesses a significant drawback such as a significative level of residual immunogenicity that must be reduced or eliminated before an in vivo implantation. Several studies tried to establish a proper bovine pericardium pre-implantation treatment to avoid the immunogenic response of the recipient: the utilization of glutaraldehyde solutions has already been used for over 60 years with positive outcomes. Notwithstanding, glutaraldehyde is responsible for promoting undesirable effects such as calcification, as well as incremental exposure over time of previously masked antigenic epitopes. In this field, it is therefore understandable the need for new pre-implantation solutions to improve pericardial tissue biocompatibility, overcoming the already existing GA side effects. With these assumptions, my thesis came to life during an internship at Biocompatibility Innovation (BCI, Este, Padua), an innovative biotechnology PMI developing technologies for the improvement of the biocompatibility degree of implantable medical devices (both of biological or synthetic origin). The study aimed to highlight the effects (biochemical and biomechanical) that polyphenols-based solution (BCI’s intellectual property) has on pre-processed bovine pericardial tissues in the way to reduce tissue immunogenicity when implanted in humans. The pre-processing and the subsequent polyphenolic mixture treatments are deeply investigated evaluating their chemical and biochemical effects. Treated tissues are also analyzed from a histological and biomechanical point of view. To ensure industrial secrecy and duly protect the developed know-how of BCI, many laboratory protocols concerning the performed treatments can not be described in detail.
I patch pericardici rappresentano i principali dispositivi medici utilizzati in campo cardiovascolare. Il pericardio di origine autologa, allogenica e xenogenica è il tessuto più utilizzato per sostituire, rigenerare e riparare strutture cardiovascolari danneggiate. Tra gli altri, il pericardio bovino è il tessuto di origine xenogenica a maggiore frequenza di utilizzo nella pratica chirurgica. Per gli innumerevoli vantaggi che la sua applicazione ha comportato, è stato ampiamente sfruttato per applicazioni cardiovascolari come endoarterectomie, chiusure arteriose e produzione di valvole bioprotesiche. Nonostante il suo ampio impiego in pratica clinica, il suo utilizzo comporta di poter incorrere in inconvenienti dovuti a caratteristiche intrinseche del tessuto come un elevato livello di immunogenicità residuo che necessita quindi di essere mitigato o eliminato prima di un impianto in vivo. Numerosi studi in letteratura hanno tentato di identificare un adeguato protocollo per il trattamento pre-impianto di tessuti pericardici che permettesse di evitare una risposta immunogenica indesiderata da parte del ricevente: in questo senso il trattamento con glutaraldeide è utilizzato con buoni risultati da oltre 60 anni. Nonostante ciò, la glutaraldeide provoca effetti indesiderati come uno stimolo alla calcificazione peri-implantare ed una esposizione incrementale nel tempo dei siti antigenici inizialmente mascherati. In questo senso, è quindi chiaramente comprensibile l’impellente necessità di introdurre nuove soluzioni di pre-trattamento che permettano di migliorare la biocompatibilità di tessuti pericardici, surclassando gli effetti indesiderati legati all’impiego della glutaraldeide. È in questa luce che la mia tesi ha preso vita durante un periodo di tirocinio presso Biocompatibility Innovation (BCI, Este, Padova), una innovativa PMI biotecnologica avente come obiettivo quello di sviluppare tecnologie per il miglioramento dei livelli di biocompatibilità dei dispositivi medici impiantabili (biologici e sintetici). Il presente studio ha come scopo quello di sottolineare gli effetti (biochimici e biomeccanici) che soluzioni a base di polifenoli (di proprietà intellettuale BCI) hanno su tessuti pericardici pre-processati allo scopo di ridurre l’immunogenicità del tessuto in ricevente umano. I trattamenti di pre-processing e a base di polifenoli, insieme alle conseguenze ad essi connessi (di tipo chimico e biochimico) sono descritti e valutati in dettaglio. I tessuti trattati sono anche analizzati da un punto di vista istologico e biomeccanico. Per ragioni di segreto industriale e per proteggere debitamente il know-how aziendale, molti protocolli relativi alle soluzioni utilizzate non verranno descritti in dettaglio.
Innovative polyphenols-based treatment for bovine pericardium biocompatibility improvement
MANZOLI, SARA
2022/2023
Abstract
Pericardial patches are the main representative of the most used implantable medical devices in the cardiovascular field. Autologous, allogeneic, and xenogeneic are the mainly exploited sources for pericardial harvesting to repair, regenerate, and replace damaged or harmed cardiovascular anatomical structures. Among the others, the bovine pericardium is the most used xenogeneic tissue in surgical practice. It has been widely employed for cardiovascular applications, such as endarterectomies, arterial closure, and bioprosthetic valve production due to its numerous advantages. Despite its extensive application, it inherently possesses a significant drawback such as a significative level of residual immunogenicity that must be reduced or eliminated before an in vivo implantation. Several studies tried to establish a proper bovine pericardium pre-implantation treatment to avoid the immunogenic response of the recipient: the utilization of glutaraldehyde solutions has already been used for over 60 years with positive outcomes. Notwithstanding, glutaraldehyde is responsible for promoting undesirable effects such as calcification, as well as incremental exposure over time of previously masked antigenic epitopes. In this field, it is therefore understandable the need for new pre-implantation solutions to improve pericardial tissue biocompatibility, overcoming the already existing GA side effects. With these assumptions, my thesis came to life during an internship at Biocompatibility Innovation (BCI, Este, Padua), an innovative biotechnology PMI developing technologies for the improvement of the biocompatibility degree of implantable medical devices (both of biological or synthetic origin). The study aimed to highlight the effects (biochemical and biomechanical) that polyphenols-based solution (BCI’s intellectual property) has on pre-processed bovine pericardial tissues in the way to reduce tissue immunogenicity when implanted in humans. The pre-processing and the subsequent polyphenolic mixture treatments are deeply investigated evaluating their chemical and biochemical effects. Treated tissues are also analyzed from a histological and biomechanical point of view. To ensure industrial secrecy and duly protect the developed know-how of BCI, many laboratory protocols concerning the performed treatments can not be described in detail.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/54128