Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Division of Dermatology, Department of Medicine David Geffen School of Medicine University of California Los Angeles, Los Angeles, CA, 90095, USA.
Adv Healthc Mater. 2024 Oct;13(25):e2302477. doi: 10.1002/adhm.202302477. Epub 2023 Nov 27.
Hydrogels are widely used for tissue engineering applications to support cellular growth, yet the tightly woven structure often restricts cell infiltration and expansion. Consequently, granular hydrogels with microporous architectures have emerged as a new class of biomaterial. Particularly, the development of microporous annealed particle (MAP) hydrogel scaffolds has shown improved stability and integration with host tissue. However, the predominant use of spherically shaped particles limits scaffold porosity, potentially limiting the level of cell infiltration. Here, a novel microporous annealed crescent-shaped particle (MAC) scaffold that is predicted to have improved porosity and pore interconnectivity in silico is presented. With microfluidic fabrication, tunable cavity sizes that optimize interstitial void space features are achieved. In vitro, cells incorporated into MAC scaffolds form extensive 3D multicellular networks. In vivo, the injectable MAC scaffold significantly enhances cell infiltration compared to spherical MAP scaffolds, resulting in increased numbers of myofibroblasts and leukocytes present within the gel without relying on external biomolecular chemoattractants. The results shed light on the critical role of particle shape in cell recruitment, laying the foundation for MAC scaffolds as a next-generation granular hydrogel for diverse tissue engineering applications.
水凝胶广泛应用于组织工程,以支持细胞生长,但紧密编织的结构常常限制细胞的渗透和扩张。因此,具有微孔结构的颗粒水凝胶已成为一类新型生物材料。特别是微孔退火颗粒(MAP)水凝胶支架的发展显示出了更好的稳定性和与宿主组织的整合性。然而,球形颗粒的主要使用限制了支架的孔隙率,可能限制了细胞的渗透水平。在这里,提出了一种新型的微孔退火新月形颗粒(MAC)支架,其在计算机模拟中具有更好的孔隙率和孔连通性。通过微流控制造,可以实现优化的间质空隙特征的可调腔室尺寸。在体外,细胞整合到 MAC 支架中形成广泛的 3D 多细胞网络。在体内,与球形 MAP 支架相比,可注射的 MAC 支架显著增强了细胞的渗透,导致凝胶内存在的肌成纤维细胞和白细胞数量增加,而无需依赖外部生物分子趋化剂。这些结果揭示了颗粒形状在细胞募集中的关键作用,为 MAC 支架作为下一代用于各种组织工程应用的颗粒水凝胶奠定了基础。
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