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Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.

ABSTRACT: The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion.

SUBMITTER: Wei Z

PROVIDER: S-EPMC10721650 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.

Wei Zhao Z Lei Meng M Wang Yaohui Y Xie Yizhou Y Xie Xueyong X Lan Dongwei D Jia Yuanbo Y Liu Jingyi J Ma Yufei Y Cheng Bo B Gerecht Sharon S Xu Feng F

Nature communications 20231214 1

The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, ...[more]

PMID: 38097553

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Project description:Anisotropic scaffolds with unidirectionally aligned fibers present an optimal solution for nerve tissue engineering and graft repair. This study investigates the application of filamented light (FLight) biofabrication to create hydrogel matrices featuring highly aligned microfilaments, facilitating neurite guidance and outgrowth from encapsulated chicken dorsal root ganglion (DRG) cells. FLight employs optical modulation instability (OMI) to rapidly and safely (<5 s) fabricate hydrogel constructs with precise microfilament alignment. The tunability of FLight matrices was demonstrated by adjusting four key parameters: stiffness, porosity, growth factor release, and incorporation of biological cues. Matrix stiffness was fine-tuned by varying the projection light dose, yielding matrices with stiffness ranging from 0.6 to 5.7 kPa. Optimal neurite outgrowth occurred at a stiffness of 0.6 kPa, achieving an outgrowth of 2.5 mm over 4 days. Matrix porosity was modified using diffraction gratings in the optical setup. While significant differences in neurite outgrowth and alignment were observed between bulk and FLight gels, further increases in porosity from 40 % to 70 % enhanced cell migration and axon bundling without significantly affecting maximal outgrowth. The incorporation of protein microcrystals containing nerve growth factor (NGF) into the photoresin enabled sustained neurite outgrowth without the need for additional NGF in the media. Finally, laminin was added to the resin to enhance the bioactivity of the biomaterial, resulting in a further increase in maximum neurite outgrowth to 3.5 mm after 4 days of culture in softer matrices. Overall, the varied matrix properties achieved through FLight significantly enhance neurite outgrowth, highlighting the importance of adaptable scaffold characteristics for guiding neurite development. This demonstrates the potential of FLight as a versatile platform for creating ideal matrices for clinical applications in nerve repair and tissue engineering.

Dataset Information

Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.

Publications

Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.

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