Improved long-term durability of allogeneic heart valves in the orthotopic sheep model

Biermann, Anna; Marzi, Julia; Brauchle, Eva; Wichmann, Julian L.; Arendt, Christophe; Püntmann, Valentina O.; Nagel, Eike; Abdel‐Aziz, Salah A.; Winter, Andreas; Brockbank, Kelvin G.M.; Layland, Shannon L.; Schenke‐Layland, Katja; Stock, Ulrich A.

doi:10.1093/ejcts/ezy292

Cited by 20 publications

(15 citation statements)

References 24 publications

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“…hTEMs and other, conceptually comparable acellular technologies have demonstrated strong over time endothelialization following implantation in recent preclinical studies ( Syedain et al, 2017 ; Biermann et al, 2019 ) , . However, despite this potential, evidence in the human setting remains preliminary ( Shirzad et al, 2017 ) and a systematical investigation in larger clinical studies are needed.…”

Section: Discussionmentioning

confidence: 99%

“…Next-generation tissue-engineered (TE) replacements with regenerative capacities ( Dahl et al, 2011 ; Weber et al, 2013 ; Driessen-Mol et al, 2014 ; Syedain et al, 2014 ; Syedain et al, 2015 ; Reimer et al, 2017 ; Syedain et al, 2017 ; Emmert et al, 2018 ; Lintas et al, 2018 ; Motta et al, 2018 ; Biermann et al, 2019 ; Boethig et al, 2019 ; Kirkton et al, 2019 ; Motta et al, 2019 ; Gerdisch et al, 2020 ; Fioretta et al, 2021 ; Syedain et al, 2021 ) have demonstrated their strong potential in numerous preclinical studies and first clinical pilot trials ( Fioretta et al, 2021 ), and may therefore represent an ideal candidate to overcome the limitations of current prostheses. As one promising TE approach, we have recently introduced a biomimetic acellular tissue-engineered matrix (TEM), that is, manufactured from a polymer composite and an in vitro grown extracellular matrix (ECM), which can be engineered from different (human) cell sources ( Emmert et al, 2018 ; Fioretta et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications

Motta

Zaytseva

Fioretta

et al. 2022

Front. Bioeng. Biotechnol.

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Hemocompatibility of cardiovascular implants represents a major clinical challenge and, to date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from human-cell-derived tissue-engineered extracellular matrices (hTEMs) demonstrated their recellularization capacity in vivo and may represent promising candidates to avoid antithrombotic therapy. To further enhance their hemocompatibility, we tested hTEMs pre-endothelialization potential using human-blood-derived endothelial-colony-forming cells (ECFCs) and umbilical vein cells (control), cultured under static and dynamic orbital conditions, with either FBS or hPL. ECFCs performance was assessed via scratch assay, thereby recapitulating the surface damages occurring in transcatheter valves during crimping procedures. Our study demonstrated: feasibility to form a confluent and functional endothelium on hTEMs with expression of endothelium-specific markers; ECFCs migration and confluency restoration after crimping tests; hPL-induced formation of neo-microvessel-like structures; feasibility to pre-endothelialize hTEMs-based TEHVs and ECFCs retention on their surface after crimping. Our findings may stimulate new avenues towards next-generation pre-endothelialized implants with enhanced hemocompatibility, being beneficial for selected high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications

Motta

Zaytseva

Fioretta

et al. 2022

Front. Bioeng. Biotechnol.

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“…Devitalization, obtained by physical processing such as freeze–thaw cycles or freezer-milling, disrupts cellular and nuclear membranes but may not fully remove DNA moieties, cell-associated proteins, and other cell remnants [ 10 ]. In addition to a potential immune rejection risk, a limited porosity of devitalized tissues poses a challenge for cell infiltration and tissue integration [ 13 , 14 , 15 ]. Therefore, the ultimate goal of decellularization is to rid the ECM of cells and genetic materials, limiting the immune risk [ 11 , 12 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial and Immunomodulatory Properties of Acellular Wharton’s Jelly Matrix

et al. 2022

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Of all biologic matrices, decellularized tissues have emerged as a promising tool in the field of regenerative medicine. Few empirical clinical studies have shown that Wharton’s jelly (WJ) of the human umbilical cord promotes wound closure and reduces wound-related infections. In this scope, we herein investigated whether decellularized (DC)-WJ could be used as an engineered biomaterial. In comparison with devitalized (DV)-WJ, our results showed an inherent effect of DC-WJ on Gram positive (S. aureus and S. epidermidis) and Gram negative (E. coli and P. aeruginosa) growth and adhesion. Although DC-WJ activated the neutrophils and monocytes in a comparable magnitude to DV-WJ, macrophages modulated their phenotypes and polarization states from the resting M0 phenotype to the hybrid M1/M2 phenotype in the presence of DC-WJ. M1 phenotype was predominant in the presence of DV-WJ. Finally, the subcutaneous implantation of DC-WJ showed total resorption after three weeks of implantation without any sign of foreign body reaction. These significant data shed light on the potential regenerative application of DC-WJ in providing a suitable biomaterial for tissue regenerative medicine and an ideal strategy to prevent wound-associated infections.

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“…In situ tissue engineering or endogenous tissue restoration might be the solution, as in this method a degradable biomaterial is implanted in the patient to temporarily function as both, graft and scaffold for endogenous cells, directing regeneration directly at the intended site in the body ( 3 ). Biomaterials applied in in situ tissue engineering range from polymer scaffolds to in vitro generated matrices and decellularized xeno- or allografts ( 4 – 6 ). Over time the biomaterial will degrade, while matrix is produced by the cells that infiltrate and populate the scaffold.…”

Section: Introductionmentioning

confidence: 99%

Marker-Independent Monitoring of in vitro and in vivo Degradation of Supramolecular Polymers Applied in Cardiovascular in situ Tissue Engineering

Marzi

Schmidt

Brauchle

et al. 2022

Front. Cardiovasc. Med.

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The equilibrium between scaffold degradation and neotissue formation, is highly essential for in situ tissue engineering. Herein, biodegradable grafts function as temporal roadmap to guide regeneration. The ability to monitor and understand the dynamics of degradation and tissue deposition in in situ cardiovascular graft materials is therefore of great value to accelerate the implementation of safe and sustainable tissue-engineered vascular grafts (TEVGs) as a substitute for conventional prosthetic grafts. In this study, we investigated the potential of Raman microspectroscopy and Raman imaging to monitor degradation kinetics of supramolecular polymers, which are employed as degradable scaffolds in in situ tissue engineering. Raman imaging was applied on in vitro degraded polymers, investigating two different polymer materials, subjected to oxidative and enzymatically-induced degradation. Furthermore, the method was transferred to analyze in vivo degradation of tissue-engineered carotid grafts after 6 and 12 months in a sheep model. Multivariate data analysis allowed to trace degradation and to compare the data from in vitro and in vivo degradation, indicating similar molecular observations in spectral signatures between implants and oxidative in vitro degradation. In vivo degradation appeared to be dominated by oxidative pathways. Furthermore, information on collagen deposition and composition could simultaneously be obtained from the same image scans. Our results demonstrate the sensitivity of Raman microspectroscopy to determine degradation stages and the assigned molecular changes non-destructively, encouraging future exploration of this techniques for time-resolved quality assessment of in situ tissue engineering processes.

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Improved long-term durability of allogeneic heart valves in the orthotopic sheep model

Abstract: IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.

Cited by 20 publications

References 24 publications

Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications

Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications

Antibacterial and Immunomodulatory Properties of Acellular Wharton’s Jelly Matrix

Marker-Independent Monitoring of in vitro and in vivo Degradation of Supramolecular Polymers Applied in Cardiovascular in situ Tissue Engineering

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