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Puncturing of lyophilized tissue engineered vascular matrices enhances the efficiency of their recellularization


Ksiazek, Agnieszka A; Frese, Laura; Dijkman, Petra E; Sanders, Bart; Motta, Sarah E; Weber, Benedikt; Hoerstrup, Simon P (2018). Puncturing of lyophilized tissue engineered vascular matrices enhances the efficiency of their recellularization. Acta Biomaterialia, 71:474-485.

Abstract

Data on in vitro engineered "off the shelf" matrices support the concept of endogenous cellular repopulation driving the graft's remodeling via immune-mediated response. This seems important to further accelerate the cell reconstitution and may play a crucial role when mononuclear cells are used. Nevertheless, studies on decellularized xenogeneic grafts showed only limited host cell repopulation post-implantation. This study aims at a systematic comparison of reseeding methods (dripping, injection, bathing in a cell suspension and combined puncturing-dripping method) to define the most efficient technique enhancing recellularization of tissue engineered vascular matrices (patches, vessels, small diameter and standard size valves) prior implantation. The constructs were analyzed histologically, biochemically and biomechanically. Various preconditioning treatments (wet, lyophilized and air-dried) combined with reseeding methods demonstrated the highest cell loading efficiency, despite applied crimping and flow stress, of lyophilization followed by puncturing-dripping technique. This novel seeding method allows for an efficient, time saving graft reseeding that can be used within a one-step cardiovascular clinical intervention.

STATEMENT OF SIGNIFICANCE

The concept of living tissue engineered, self-repairing, autologous cardiovascular replacements, was proposed alternatively to existing synthetic/xenogeneic prostheses. Recent studies in animal models demonstrate faster in vivo recellularization after grafts pre-seeding with cells prior implantation. Pre-seeded cells hold either, the ability to differentiate directionally or attract host cells, crucial for graft integration and remodeling. It is unclear, however, how efficient the pre-loading is and how well cells withstand the flow. The study presents a systematic overview on cell loading techniques of different cardiovascular constructs, tested under static and dynamic conditions. Comparison illustrates a significantly higher efficiency of cells loading in lyophilized tissues punctured before their standard seeding. This technique may beneficially accelerate remodeling of cardiovascular grafts in further in vivo studies.

Abstract

Data on in vitro engineered "off the shelf" matrices support the concept of endogenous cellular repopulation driving the graft's remodeling via immune-mediated response. This seems important to further accelerate the cell reconstitution and may play a crucial role when mononuclear cells are used. Nevertheless, studies on decellularized xenogeneic grafts showed only limited host cell repopulation post-implantation. This study aims at a systematic comparison of reseeding methods (dripping, injection, bathing in a cell suspension and combined puncturing-dripping method) to define the most efficient technique enhancing recellularization of tissue engineered vascular matrices (patches, vessels, small diameter and standard size valves) prior implantation. The constructs were analyzed histologically, biochemically and biomechanically. Various preconditioning treatments (wet, lyophilized and air-dried) combined with reseeding methods demonstrated the highest cell loading efficiency, despite applied crimping and flow stress, of lyophilization followed by puncturing-dripping technique. This novel seeding method allows for an efficient, time saving graft reseeding that can be used within a one-step cardiovascular clinical intervention.

STATEMENT OF SIGNIFICANCE

The concept of living tissue engineered, self-repairing, autologous cardiovascular replacements, was proposed alternatively to existing synthetic/xenogeneic prostheses. Recent studies in animal models demonstrate faster in vivo recellularization after grafts pre-seeding with cells prior implantation. Pre-seeded cells hold either, the ability to differentiate directionally or attract host cells, crucial for graft integration and remodeling. It is unclear, however, how efficient the pre-loading is and how well cells withstand the flow. The study presents a systematic overview on cell loading techniques of different cardiovascular constructs, tested under static and dynamic conditions. Comparison illustrates a significantly higher efficiency of cells loading in lyophilized tissues punctured before their standard seeding. This technique may beneficially accelerate remodeling of cardiovascular grafts in further in vivo studies.

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Additional indexing

Item Type:Journal Article["page:refereed_set_refereed" not defined]["page:subtype_original" not defined]
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2 March 2018
Deposited On:19 Mar 2018 18:44
Last Modified:13 Apr 2018 11:42
Publisher:Elsevier
ISSN:1742-7061
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.actbio.2018.02.029
PubMed ID:29505888
Project Information:
  • : FunderFP7
  • : Grant ID242008
  • : Project TitleLIFEVALVE - Living autologous heart valves for minimally invasive implantable procedures
  • : FunderFP7
  • : Grant ID626976
  • : Project TitleLIVAGRAFT - Improvement of the clinical applicability of tissue-engineered vascular grafts, as new regenerative therapy for children with congenital cardiovascular malformations

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