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Composite scaffold provides a cell delivery platform for cardiovascular repair.

ABSTRACT: Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-? promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.

SUBMITTER: Godier-Furnemont AF

PROVIDER: S-EPMC3093484 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other

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Composite scaffold provides a cell delivery platform for cardiovascular repair.

Godier-Furnémont Amandine F G AF Martens Timothy P TP Koeckert Michael S MS Wan Leo L Parks Jonathan J Arai Kotaro K Zhang Geping G Hudson Barry B Homma Shunichi S Vunjak-Novakovic Gordana G

Proceedings of the National Academy of Sciences of the United States of America 20110420 19

Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin ...[more]

PMID: 21508321

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Project description:Controlled delivery of hydrophilic proteins is an important therapeutic strategy. However, widely used methods for protein delivery suffer from low incorporation efficiency and loss of bioactivity. The versatile interfacial polyelectrolyte complexation (IPC) fibers have the capacity for precise spatiotemporal release and protection of protein, growth factor, and cell bioactivity. Yet its weak mechanical properties limit its application and translation into a viable clinical solution. To overcome this limitation, IPC fibers can be incorporated into polymeric scaffolds such as the biocompatible poly(vinyl alcohol) hydrogel (PVA). Therefore, we explored the use of a composite scaffold of PVA and IPC fibers for controlled biomolecule release. We first observed that the permeability of biomolecules through PVA films were dependent on molecular weight. Next, IPC fibers were incorporated in between layers of PVA to produce PVA-IPC composite scaffolds with different IPC fiber orientation. The composite scaffold demonstrated excellent mechanical properties and efficient biomolecule incorporation. The rate of biomolecule release from PVA-IPC composite grafts exhibited dependence on molecular weight, with lysozyme showing near-linear release for 1 month. Angiogenic factors were also incorporated into the PVA-IPC grafts, as a potential biomedical application of the composite graft. While vascular endothelial growth factor only showed a maximum cumulative release of 3%, the smaller PEGylated-QK peptide showed maximum release of 33%. Notably, the released angiogenic biomolecules induced endothelial cell activity thus indicating retention of bioactivity. We also observed lack of significant macrophage response against PVA-IPC grafts in a rabbit model. Showing permeability, mechanical strength, precise temporal growth factor release, and bioinertness, PVA-IPC fibers composite scaffolds are excellent scaffolds for controlled biomolecule delivery in soft tissue engineering.

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Composite scaffold provides a cell delivery platform for cardiovascular repair.

Publications

Composite scaffold provides a cell delivery platform for cardiovascular repair.

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