A Biomimetic Approach Utilizing Pulsatile Perfusion Generates Contractile Vascular Grafts

Surgical implantation of decellularized cadaveric arteries is routinely used to treat right-sided congenital cardiac lesions. These acellular conduits lack the capacity for somatic growth and are prone to stenosis and calcification, necessitating multiple operations throughout childhood. Islet-1+ ca...

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Published in:Tissue engineering. Part A 2023-07, Vol.29 (13-14), p.358-371
Main Authors: Knox, Cole, Garcia, Keren, Tran, Jade, Wilson, Sean M, Blood, Arlin B, Kearns-Jonker, Mary, Martens, Timothy P
Format: Article
Language:English
Subjects:
Bioreactors
Cadavers
Calcification
Calponin
Cell culture
Cell differentiation
Children
Elastin
Endothelium
Extracellular matrix
Grafts
Heart
Immunohistochemistry
Islet-1 protein
Mechanical properties
Muscle contraction
Myosin
Phenotypes
Polymerase chain reaction
Progenitor cells
Pulmonary arteries
Pulmonary artery
Smooth muscle
Stenosis
Transplantation
Veins & arteries
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Summary:Surgical implantation of decellularized cadaveric arteries is routinely used to treat right-sided congenital cardiac lesions. These acellular conduits lack the capacity for somatic growth and are prone to stenosis and calcification, necessitating multiple operations throughout childhood. Islet-1+ cardiovascular progenitor cells (CPCs) have demonstrated the capacity for differentiation into all cell types of the heart and outflow tracts. We hypothesize that CPC seeding of decellularized pulmonary arteries and bioreactor culture under physiologic flow conditions will drive vascular differentiation of CPCs and result in a conduit more suitable for implantation and long-term growth. We began by decellularizing ovine pulmonary arteries and characterizing the composition of the extracellular matrix (ECM). Hemodynamic testing of decellularized vessels in a custom bioreactor was used to define the scaffold mechanical properties over a range of pressures and flow rates. Next, our expanded ovine CPCs were suspended in growth media and injected intramurally into decellularized pulmonary arteries that were subsequently cultured in either static or pulsatile cultures. A combination of immunohistochemistry, real-time polymerase chain reaction (PCR), and tissue bath contraction studies were used to evaluate the bioengineered arteries before transplantation. Pulmonary artery patches from the most favorable culture conditions were then implanted into juvenile sheep to provide proof of concept. Hematoxylin and eosin staining indicated complete removal of cell nuclei (  = 9), whereas double-stranded DNA isolation from tissue homogenates showed 99.1% DNA removal (  
ISSN:1937-3341
1937-335X
DOI:10.1089/ten.tea.2022.0206