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Decellularized extracellular matrix materials for treatment of ischemic cardiomyopathy.

ABSTRACT: Ischemic cardiomyopathy (ICM) affect millions of patients globally. Decellularized extracellular matrix materials (dECM) have components, microstructure and mechanical properties similar to healthy cardiac tissues, and can be manufactured into various forms of implantable biomaterials including injectable hydrogels or epicardial patches, which have been extensively reported to attenuate pathological left ventricular remodeling and maintain heart function. Recently, dECM medical devices for ICM treatment have been approved for clinical use or studied in clinical trials, exhibiting considerable translation potential. Cells, growth factors and other bioactive agents have been incorporated with different dECM materials to improve the therapeutic outcomes. In addition, more detailed aspects of the biological effects and mechanisms of dECM treatment are being revealed. This review summarized recent advances in dECM materials from variable sources for cardiac repair, including extraction of extracellular matrix, cell integration, smart manufacturing of injectable hydrogels and cardiac patch materials, and their therapeutic applications. Besides, this review provides an outlook on the cutting-edge development directions in the field.

SUBMITTER: Liu W

PROVIDER: S-EPMC10697850 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Decellularized extracellular matrix materials for treatment of ischemic cardiomyopathy.

Liu Wei W Zhang Xiangmei X Jiang Xiaokai X Dai Binyao B Zhang Liwen L Zhu Yang Y

Bioactive materials 20231129

Ischemic cardiomyopathy (ICM) affect millions of patients globally. Decellularized extracellular matrix materials (dECM) have components, microstructure and mechanical properties similar to healthy cardiac tissues, and can be manufactured into various forms of implantable biomaterials including injectable hydrogels or epicardial patches, which have been extensively reported to attenuate pathological left ventricular remodeling and maintain heart function. Recently, dECM medical devices for ICM t ...[more]

PMID: 38076651

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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.

Project description:Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in decellularized lungs, is poorly understood. Using a commonly utilized detergent-based decellularization approach in human autopsy lungs resulted in disproportionate losses of GAGs with depletion of chondroitin sulfate/dermatan sulfate (CS/DS) > heparan sulfate (HS) > hyaluronic acid (HA). Specific changes in disaccharide composition of remaining GAGs were observed with disproportionate loss of NS and NS2S for HS groups and of 4S for CS/DS groups. No significant influence of smoking history, sex, time to autopsy, or age was observed in native vs. decellularized lungs. Notably, surface plasmon resonance demonstrated that GAGs remaining in decellularized lungs were unable to bind key matrix-associated growth factors FGF2, HGF, and TGFβ1. Growth of lung epithelial, pulmonary vascular, and stromal cells cultured on the surface of or embedded within gels derived from decellularized human lungs was differentially and combinatorially enhanced by replenishing specific GAGs and FGF2, HGF, and TGFβ1. In summary, lung decellularization results in loss and/or dysfunction of specific GAGs or side chains significantly affecting matrix-associated growth factor binding and lung cell metabolism. GAG and matrix-associated growth factor replenishment thus needs to be incorporated into schemes for investigations utilizing gels and other materials produced from decellularized human lungs. STATEMENT OF SIGNIFICANCE: Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in decellularized lungs, is poorly understood. In the current studies, we demonstrate that glycosaminoglycans (GAGs) are significantly depleted during decellularization and those that remain are dysfunctional and unable to bind matrix-associated growth factors critical for cell growth and differentiation. Systematically repleting GAGs and matrix-associated growth factors to gels derived from decellularized human lung significantly and differentially affects cell growth. These studies highlight the importance of considering GAGs in decellularized lungs and their derivatives.

Dataset Information

Decellularized extracellular matrix materials for treatment of ischemic cardiomyopathy.

Publications

Decellularized extracellular matrix materials for treatment of ischemic cardiomyopathy.

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