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Biodegradable nanofibrous temperature-responsive gelling microspheres for heart regeneration.

ABSTRACT: Myocardial infarction (heart attack) is the number one killer of heart patients. Existing treatments for heart attack do not address the underlying problem of cardiomyocyte (CM) loss and cannot regenerate the myocardium. Introducing exogenous cardiac cells is required for heart regeneration due to the lack of resident progenitor cells and very limited proliferative potential of adult CMs. Poor retention of transplanted cells is the critical bottleneck of heart regeneration. Here, we report the invention of a poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(N-Isopropylacrylamide) copolymer and its self-assembly into nanofibrous gelling microspheres (NF-GMS). The NF-GMS undergo thermally responsive transition to form not only a 3D hydrogel after injection in vivo, but also exhibit architectural and structural characteristics mimicking the native extracellular matrix (ECM) of nanofibrous proteins and gelling proteoglycans or polysaccharides. By integrating the ECM-mimicking features, injectable form, and the capability of maintaining 3D geometry after injection, the transplantation of hESC-derived CMs carried by NF-GMS led to a striking 10-fold graft size increase over direct CM injection in an infarcted rat model, which is the highest reported engraftment to date. Furthermore, NF-GMS carried CM transplantation dramatically reduced infarct size, enhanced integration of transplanted CMs, stimulated vascularization in the infarct zone, and led to a substantial recovery of cardiac function. The NF-GMS may also serve as advanced injectable and integrative biomaterials for cell/biomolecule delivery in a variety of biomedical applications.

SUBMITTER: Zhao C

PROVIDER: S-EPMC7567402 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:UnlabelledThe aim of this study was to investigate the effects of PLLA nanofibrous microspheres (NF-MS) as a cell delivery carrier in combination with controlled release of BMP-2 from PLGA microspheres on the induction of odontogenic differentiation of human stem cells of apical papilla (SCAP). Injectable NF-MS, which mimic the physical architecture of collagen fibers on the nano scale, were fabricated by combining thermally-induced phase separation techniques with an emulsification process. SCAP cultured in a monolayer or cultured on NF-MS in spinner flasks were treated with 100ng/ml BMP-2 in vitro. Odontogenic differentiation was characterized by measuring alkaline phosphatase activity, odontogenic gene expression levels, calcium content, and dentin sialophosphoprotein accumulation. The results demonstrated that BMP-2 enhanced human SCAP odontogenic differentiation both in monolayer culture and on 3D NF-MS in spinner flask culture in vitro. We also developed and tested a system combining NF-MS with controlled BMP-2 release for dentin regeneration in vivo. The results indicate that controlled release of BMP-2 promoted more mineralization and osteodentin formation compared to a BSA-releasing control in a dose-dependent and time-dependent manner. In summary, the NF-MS combined with controlled release of BMP-2 provides an excellent microenvironment for SCAP to regenerate dentin tissue.Statement of significanceTooth lesion and loss affect masticatory efficiency, speaking function, facial aesthetics and even psychological health. Current treatments depend on "inert" restorative materials, which do not have the healing capacity and may lead to the failure of the restorations over a long term. The aim of this study was to develop an injectable biomaterial and desired growth factor delivery system to support stem cells for mineralized dental tissue regeneration. The study showed that novel injectable and biodegradable nanofibrous microspheres and controlled release of BMP-2 synergistically induce the odontogenic differentiation of human stem cells from the apical papilla and mineralized tissue regeneration, demonstrating the potential of living dental tissue repair.

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Biodegradable nanofibrous temperature-responsive gelling microspheres for heart regeneration.

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