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Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture.

ABSTRACT: Hepatocellular carcinoma (HCC), as the fifth most common malignant cancer, develops and progresses mostly in a cirrhotic liver where stiff nodules are separated by fibrous bands. Scaffolds that can provide a 3D cirrhotic mechanical environment with complex native composition and biomimetic architecture are necessary for the development of better predictive tissue models. Here, we developed photocrosslinkable liver decellularized extracellular matrix (dECM) and a rapid light-based 3D bioprinting process to pattern liver dECM with tailorable mechanical properties to serve as a platform for HCC progression study. 3D bioprinted liver dECM scaffolds were able to stably recapitulate the clinically relevant mechanical properties of cirrhotic liver tissue. When encapsulated in dECM scaffolds with cirrhotic stiffness, HepG2 cells demonstrated reduced growth along with an upregulation of invasion markers compared to healthy controls. Moreover, an engineered cancer tissue platform possessing tissue-scale organization and distinct regional stiffness enabled the visualization of HepG2 stromal invasion from the nodule with cirrhotic stiffness. This work demonstrates a significant advancement in rapid 3D patterning of complex ECM biomaterials with biomimetic architecture and tunable mechanical properties for in vitro disease modeling.

SUBMITTER: Ma X

PROVIDER: S-EPMC6186504 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture.

Ma Xuanyi X Yu Claire C Wang Pengrui P Xu Weizhe W Wan Xueyi X Lai Cheuk Sun Edwin CSE Liu Justin J Koroleva-Maharajh Anna A Chen Shaochen S

Biomaterials 20180918

Hepatocellular carcinoma (HCC), as the fifth most common malignant cancer, develops and progresses mostly in a cirrhotic liver where stiff nodules are separated by fibrous bands. Scaffolds that can provide a 3D cirrhotic mechanical environment with complex native composition and biomimetic architecture are necessary for the development of better predictive tissue models. Here, we developed photocrosslinkable liver decellularized extracellular matrix (dECM) and a rapid light-based 3D bioprinting ...[more]

PMID: 30265900

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Project description:RationalePerfusion decellularization of cadaveric hearts removes cells and generates a cell-free extracellular matrix scaffold containing acellular vascular conduits, which are theoretically sufficient to perfuse and support tissue-engineered heart constructs. However, after transplantation, these acellular vascular conduits clot, even with anti-coagulation. Here, our objective was to create a less thrombogenic scaffold and improve recellularized-left ventricular contractility by re-lining vascular conduits of a decellularized rat heart with rat aortic endothelial cells (RAECs).Methods and resultsWe used three strategies to recellularize perfusion-decellularized rat heart vasculature with RAECs: retrograde aortic infusion, brachiocephalic artery (BA) infusion, or a combination of inferior vena cava (IVC) plus BA infusion. The re-endothelialized scaffolds were maintained under vascular flow in vitro for 7 days, and then cell morphology, location, and viability were examined. Thrombogenicity of the scaffold was assessed in vitro and in vivo. Both BA and IVC+BA cell delivery resulted in a whole heart distribution of RAECs that proliferated, retained an endothelial phenotype, and expressed endothelial nitric oxide synthase and von Willebrand factor. Infusing RAECs via the combination IVC+BA method increased scaffold cellularity and the number of vessels that were lined with endothelial cells; re-endothelialization by using BA or IVC+BA cell delivery significantly reduced in vitro thrombogenicity. In vivo, both acellular and re-endothelialized scaffolds recruited non-immune host cells into the organ parenchyma and vasculature. Finally, re-endothelialization before recellularization of the left ventricular wall with neonatal cardiac cells enhanced construct contractility.ConclusionsThis is the first study to re-endothelialize whole decellularized hearts throughout both arterial and venous beds and cavities by using arterial and venous delivery. The combination (IVC+BA) delivery strategy results in enhanced scaffold vessel re-endothelialization compared to single-route strategies. Re-endothelialization reduced scaffold thrombogencity and improved contractility of left ventricular-recellularized constructs. Thus, vessel and cavity re-endothelialization creates superior vascularized scaffolds for use in whole-organ recellularization applications.

Dataset Information

Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture.

Publications

Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture.

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