Controlling Microparticle Aspect Ratio via Photolithography for Injectable Granular Hydrogel Formation and Cell Delivery.

IF 5.4 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Biomaterials Science & Engineering Pub Date : 2025-01-09 DOI:10.1021/acsbiomaterials.4c02102

Dean E Stornello, Jun Kim, Zhiyuan Chen, Kyle Heaton, Taimoor H Qazi

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引用次数: 0

Abstract

Granular hydrogels are injectable and inherently porous biomaterials assembled through the packing of microparticles. These particles typically have a symmetric and spherical shape. However, recent studies have shown that asymmetric particles with high aspect ratios, such as fibers and rods, can significantly improve the mechanics, structure, and cell-guidance ability of granular hydrogels. Despite this, it remains unknown how controlled changes in the particle aspect ratio influence the injectability, porosity, and cell-instructive capabilities of granular hydrogels. Part of the challenge lies in obtaining microparticles with precisely tailored dimensions using fabrication methods such as flow-focusing microfluidics or extrusion fragmentation. In this work, we leveraged facile photolithography and photocurable hyaluronic acid to fabricate rod-shaped microparticles with widths and heights of 130 μm and lengths that varied from 260 to 1300 μm to obtain aspect ratios (ARs) of 2, 4, 6, 8, and 10. All AR microparticles formed porous and injectable granular hydrogels after centrifugation jamming. Interestingly, the longest microparticles neither clogged the needle nor fractured after extrusion from a syringe. This was attributed to a relatively low elastic modulus that permitted microparticle pliability and reversible deformation under shear. Cells (NIH/3T3 fibroblasts) mixed with the jammed microparticles and injected into molds remained viable, adhered to the particles' surface, and showed a significant and rapid rate of proliferation over a period of 7 days compared to bulk hydrogels. The proliferation rate and morphology of the cells were significantly influenced by the particle AR, with higher cell numbers observed with intermediate ARs, likely attributable to the surface area available for cell adhesion. These findings showcase the utility of injectable granular hydrogels made with high-aspect-ratio microparticles for biomedical applications.

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来源期刊

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