Pushing the envelope in tissue engineering: Ex vivo production of thick vascularized cardiac extracellular matrix constructs

Udi Sarig, Evelyne Bao Vi Nguyen, Yao Wang, Sherwin Ting, Tomer Bronshtein, Hadar Sarig, Nitsan Dahan, Maskit Gvirtz, Shaul Reuveny, Steve K.W. Oh, Thomas Scheper, Yin Chiang Freddy Boey, Subbu S. Venkatraman, Marcelle Machluf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Functional vascularization is a prerequisite for cardiac tissue engineering of constructs with physiological thicknesses. We previously reported the successful preservation of main vascular conduits in isolated thick acellular porcine cardiac ventricular ECM (pcECM). We now unveil this scaffold's potential in supporting human cardiomyocytes and promoting new blood vessel development ex vivo, providing long-term cell support in the construct bulk. A custom-designed perfusion bioreactor was developed to remodel such vascularization ex vivo, demonstrating, for the first time, functional angiogenesis in vitro with various stages of vessel maturation supporting up to 1.7? mm thick constructs. A robust methodology was developed to assess the pcECM maximal cell capacity, which resembled the human heart cell density. Taken together these results demonstrate feasibility of producing physiological-like constructs such as the thick pcECM suggested here as a prospective treatment for end-stage heart failure. Methodologies reported herein may also benefit other tissues, offering a valuable in vitro setting for "thick-tissue" engineering strategies toward large animal in vivo studies.

Original languageEnglish
Pages (from-to)1507-1519
Number of pages13
JournalTissue Engineering - Part A.
Volume21
Issue number9-10
DOIs
StatePublished - 1 May 2015

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