Dataset Information

Colloidal Gels with Tunable Mechanomorphology Regulate Endothelial Morphogenesis.

ABSTRACT: Endothelial morphogenesis into capillary networks is dependent on the matrix morphology and mechanical properties. In current 3D gels, these two matrix features are interdependent and their distinct roles in endothelial organization are not known. Thus, it is important to decouple these parameters in the matrix design. Colloidal gels can be engineered to regulate the microstructural morphology and mechanics in an independent manner because colloidal gels are formed by the aggregation of particles into a self-similar 3D network. In this work, gelatin based colloidal gels with distinct mechanomorphology were developed by engineering the electrostatic interaction mediated aggregation of particles. By altering the mode of aggregation, colloidal gels showed either compact dense microstructure or tenuous strand-like networks, and the matrix stiffness was controlled independently by varying the particle fraction. Endothelial Cell (EC) networks were favored in tenuous strand-like microstructure through increased cell-matrix and cell-cell interactions, while compact dense microstructure inhibited the networks. For a given microstructure, as the gel stiffness was increased, the extent of EC network was reduced. This result demonstrates that 3D matrix morphology and mechanics provide distinct signals in a bidirectional manner during EC network formation. Colloidal gels can be used to interrogate the angiogenic responses of ECs and can be developed as a biomaterial for vascularization.

SUBMITTER: Nair SK

PROVIDER: S-EPMC6355882 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Colloidal Gels with Tunable Mechanomorphology Regulate Endothelial Morphogenesis.

Nair Smruti K SK Basu Sukanya S Sen Ballari B Lin Meng-Hsuan MH Kumar Arati N AN Yuan Yuan Y Cullen Paul J PJ Sarkar Debanjan D

Scientific reports 20190131 1

Endothelial morphogenesis into capillary networks is dependent on the matrix morphology and mechanical properties. In current 3D gels, these two matrix features are interdependent and their distinct roles in endothelial organization are not known. Thus, it is important to decouple these parameters in the matrix design. Colloidal gels can be engineered to regulate the microstructural morphology and mechanics in an independent manner because colloidal gels are formed by the aggregation of particle ...[more]

PMID: 30705322

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Project description:One of the fundamental challenges in vascular morphogenesis is to understand how the microstructural morphology of a 3D matrix can provide the spatial cues to organize the endothelial cells (ECs) into specific vascular structures. Colloidal gels can provide well-controlled distinct morphological matrices because these gels are formed by the aggregation of particles. By altering the aggregation mode, the spatial organization of the particles can be controlled to yield different microstructural morphology. To demonstrate this, colloidal aggregates and gels were developed by electrostatic interaction-mediated aggregation of cationic polyurethane (PU) colloidal particles by using low molecular weight electrolyte and polyelectrolyte to develop microstructurally different colloidal gels without altering their bulk elasticity. Compact dense colloidal aggregates with constricted voids were developed via electrolyte-mediated aggregation, whereas stranded branched networks with interconnected voids were formed via polyelectrolyte-mediated bridging interactions. Results show that the microstructure of aggregated colloids and gels can regulate EC organizations. Within endothelial matrices, ECs track the microstructure of particulate phase to interconnect with stranded colloidal network but cluster around compact colloidal aggregate. Similarly, in colloidal gels, ECs formed capillary-like structures by interconnecting along the stranded networks with enhanced cell-matrix interactions and increased cell extension but aggregated within the constricted voids of compact dense gel with enhanced cell-cell interaction. Both morphometric analysis and expression of EC markers corroborated the cell organizations in these gels. Using these colloidal gels, we demonstrated the role of 3D microstructural morphology as an important regulator for spatial guidance of ECs and simultaneously established the significance of colloidal gels as 3D matrix to regulate cellular morphogenesis.

Project description:Unlike conventional monolithic hydrogels with covalent cross-linkage that are typically elastic, colloidal gels assembled by reversibly assembled particles as building blocks have shown fascinating viscoelastic properties. They follow a gel-sol transition upon yielding and recover to the initial state upon the release of the shear force (so-called shear-thinning and self-healing behavior); this makes them an ideal candidate as injectable and moldable biomaterials for tissue regeneration. The immune response provoked by the implantation of the colloidal gels with special viscoelastic and structural features is critical for the successful integration of the implants with the host tissues, which, however, remains little explored. Since macrophages are known as the primary immune cells in determining the inflammatory response against the implants, we herein investigated in vitro macrophage polarization and in vivo inflammatory response induced by gelatin-based colloidal gels as compared to monolithic gels. Specifically, self-healing colloidal gels composed of pure gelatin nanoparticles, or methacrylate gelatin (GelMA) nanoparticles to allow secondary covalent cross-linkage were compared with GelMA bulk hydrogels. We demonstrated that hydrogel's elasticity plays a more dominant role rather than the structural feature in determining in vitro macrophage polarization evidenced by the stiffer gels inducing pro-inflammation M2 macrophage phenotype as compared to soft gels. However, subcutaneous implantation revealed a significantly alleviated immune response characterized by less fibrous capsule formation for the colloidal gels as compared to bulk gels of similar matrix elasticity. We speculated this can be related to the improved permeability of the colloidal gels for cell penetration, thereby leading to less fibrosis. In general, this study provided in-depth insight into the biophysical regulator of hydrogel materials on macrophage behavior and related inflammatory response, which can further direct future implant design and predict biomaterial-host interactions for immunotherapy and regenerative medicine. Impact statement Macrophages response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Nowadays, the viscoelastic properties of colloidal versus monolithic hydrogels on macrophage phenotype in vitro and the host inflammatory response are not known. Our study found that colloidal hydrogels composed of nanoparticles of gelatin and methacrylate gelatin (GelMA) led to more anti-inflammatory polarization especially on soft colloidal gel (5.9 KPa) compared to bulk GelMA hydrogels. It suggested that macrophage response can be mechanically regulated by the viscoelastic signals of the hydrogels, which could be a promising strategy for the future design and application of novel biomaterials.

Dataset Information

Colloidal Gels with Tunable Mechanomorphology Regulate Endothelial Morphogenesis.

Publications

Colloidal Gels with Tunable Mechanomorphology Regulate Endothelial Morphogenesis.

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