In vivo performance of freeze-dried decellularized pulmonary heart valve allo- and xenografts orthotopically implanted into juvenile sheep

Goecke, Tobias; Theodoridis, Karolina; Tudorache, I.; Ciubotaru, Anatol; Cebotari, Serghei; Ramm, Robert; Höffler, Klaus; Sarikouch, Samir; Rivera, Andrés Vásquez; Haverich, Axel; Wolkers, Willem F.; Hilfiker, Andres

doi:10.1016/j.actbio.2017.11.041

Cited by 50 publications

(39 citation statements)

References 24 publications

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“…The performance of all other xenogeneic heart valves was comparable to the allogeneic doPHV previously published ( Figures 2C & 3B). 22 Macroscopically, most xenogeneic explants exhibited thin, pliable, and translucent leaflets and a shiny and smooth PA comparable to allogeneic controls ( Figure 3A). Only TX + SDS-treated valves exhibited slightly reddish, thickened, and opaque cusps ( Figure 3A).…”

Section: Hemodynamic and Clinical Performance Of Decellularized Pormentioning

confidence: 87%

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Ramm

Goecke

Theodoridis

et al. 2019

Xenotransplantation

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Background Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof. Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome. This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N‐glycan and DNA removal. Methods dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content. Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host. Allogenic doPHV implantations (n = 3) from a previous study served as control. Results Among the decellularization procedures, Triton X‐100 & SDS as well as trypsin & Triton X‐100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact. In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls. Removal of N‐linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X‐100 & SDS dpPHV, whereas this treatment of trypsin & Triton X‐100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants. Conclusion Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.

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Section: Hemodynamic and Clinical Performance Of Decellularized Pormentioning

confidence: 87%

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Ramm

Goecke

Theodoridis

et al. 2019

Xenotransplantation

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“…One third of dissected longitudinally native, decellularized, and decellularized and enzymatic treated pulmonary trunk samples (n = 3, each) were fixed in 10% (v/v) formalin, and dehydrated and embedded in paraffin. Histological sections (6 μm) were stained for hematoxylin and eosin (H&E) and Movat pentachrome, as described by Ref.,33,34 to investigate cell removal and ECM morphology.…”

Section: Histologymentioning

confidence: 99%

Toward acellular xenogeneic heart valve prostheses: Histological and biomechanical characterization of decellularized and enzymatically deglycosylated porcine pulmonary heart valve matrices

Findeisen

Morticelli

Goecke

et al. 2020

Xenotransplantation

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“…Sucrose-protected freeze-dried decellularized pulmonary heart valves were recently successfully used for transplantation in sheep in which their clinical performance was tested 23 . The valves were recovered 6 months after transplantation and found to be repopulated with autologous cells, suggesting freeze-drying does not affect the growth potential of decellularized valves.…”

Section: Discussionmentioning

confidence: 99%

“…However, pre-treatment with very high sucrose concentrations was shown to be needed (80% w/v) to avoid pore formation 22 . We have recently demonstrated that, if used for transplantation, sucrose-protected freeze-dried decellularized pulmonary heart valves show excellent clinical performance and cell repopulation potential in juvenile sheep 23 .…”

Section: Introductionmentioning

confidence: 99%

Use of sucrose to diminish pore formation in freeze-dried heart valves

Vásquez-Rivera

Oldenhof

Dipresa

et al. 2018

Sci Rep

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Freeze-dried storage of decellularized heart valves provides easy storage and transport for clinical use. Freeze-drying without protectants, however, results in a disrupted histoarchitecture after rehydration. In this study, heart valves were incubated in solutions of various sucrose concentrations and subsequently freeze-dried. Porosity of rehydrated valves was determined from histological images. In the absence of sucrose, freeze-dried valves were shown to have pores after rehydration in the cusp, artery and muscle sections. Use of sucrose reduced pore formation in a dose-dependent manner, and pretreatment of the valves in a 40% (w/v) sucrose solution prior to freeze-drying was found to be sufficient to completely diminish pore formation. The presence of pores in freeze-dried valves was found to coincide with altered biomechanical characteristics, whereas biomechanical parameters of valves freeze-dried with enough sucrose were not significantly different from those of valves not exposed to freeze-drying. Multiphoton imaging, Fourier transform infrared spectroscopy, and differential scanning calorimetry studies revealed that matrix proteins (i.e. collagen and elastin) were not affected by freeze-drying.

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In vivo performance of freeze-dried decellularized pulmonary heart valve allo- and xenografts orthotopically implanted into juvenile sheep

Cited by 50 publications

References 24 publications

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Decellularization combined with enzymatic removal of N‐linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model

Toward acellular xenogeneic heart valve prostheses: Histological and biomechanical characterization of decellularized and enzymatically deglycosylated porcine pulmonary heart valve matrices

Use of sucrose to diminish pore formation in freeze-dried heart valves

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