Guiding Oligodendrocyte Progenitor Cell Maturation Using Electrospun Fiber Cues in a 3D Hyaluronic Acid Hydrogel Culture System.

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Rachel A Mazur, Kyle J Lampe
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引用次数: 0

Abstract

The current lack of therapeutic approaches to demyelinating disorders and injuries stems from a lack of knowledge surrounding the underlying mechanisms of myelination. This knowledge gap motivates the development of effective models to study the role of environmental cues in oligodendrocyte progenitor cell (OPC) maturation. Such models should focus on determining, which factors influence OPCs to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Here, we introduce a hyaluronic acid (HA) hydrogel system composed of cross-linked HA containing encapsulated HA fibers with swollen diameters similar to mature axons (2.7 ± 0.2 μm). We tuned hydrogel storage moduli to simulate native brain tissue (200-2000 Pa) and studied the effects of fiber presence on OPC proliferation, metabolic activity, protein deposition, and morphological changes in gels of intermediate storage modulus (800 ± 0.3 Pa). OPCs in fiber-containing gels at culture days 4 and 7 exhibited a significantly greater number of process extensions, a morphological change associated with differentiation. By contrast, OPCs in fiber-free control gels maintained more proliferative phenotypes with 2.2-fold higher proliferation at culture day 7 and 1.8-fold higher metabolic activity at culture days 4 and 7. Fibers were also found to influence extracellular matrix (ECM) deposition and distribution, with more, and more distributed, nascent ECM deposition occurring in the fiber-containing gels. Overall, these data indicate that inclusion of appropriately sized HA fibers provides topographical cues, which guide OPCs toward differentiation. This HA hydrogel/fiber system is a promising in vitro scheme, providing valuable insight into the underlying mechanisms of differentiation and myelination.

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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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