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Biomater. Res., 2024 May 29:28:0032 | https://doi.org/10.34133/bmr.0032 Multiscale Control of Nanofiber-Composite Hydrogel for Complex 3D Cell Culture by Extracellular Matrix Composition and Nanofiber Alignment

Cholong Choi¹, Eunhye Yun¹, Minju Song¹, Jiyun Kim¹, Jae Sung Son², and Chaenyung Cha^1*

¹Center for Multidimensional Programmable Matter, Department of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

²Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongsangbuk-do 37673, Republic of Korea.

^*Address correspondence to: Chaenyung Cha

Abstract

In order to manipulate the complex behavior of cells in a 3-dimensional (3D) environment, it is important to provide the microenvironment that can accurately portray the complexity of highly anisotropic tissue structures. However, it is technically challenging to generate a complex microenvironment using conventional biomaterials that are mostly isotropic with limited bioactivity. In this study, the gelatin-hyaluronic acid hydrogel incorporated with aqueous-dispersible, short nanofibers capable of in situ alignment is developed to emulate the native heterogeneous extracellular matrix consisting of fibrous and non-fibrous components. The gelatin nanofibers containing magnetic nanoparticles, which could be aligned by external magnetic field, are dispersed and embedded in gelatin-hyaluronic acid hydrogel encapsulated with dermal fibroblasts. The aligned nanofibers via magnetic field could be safely integrated into the hydrogel, and the process could be repeated to generate larger 3D hydrogels with variable nanofiber alignments. The aligned nanofibers in the hydrogel can more effectively guide the anisotropic morphology (e.g., elongation) of dermal fibroblasts than random nanofibers, whereas myofibroblastic differentiation is more prominent in random nanofibers. At a given nanofiber configuration, the hydrogel composition having intermediate hyaluronic acid content induces myofibroblastic differentiation. These results indicate that modulating the degree of nanofiber alignment and the hyaluronic acid content of the hydrogel are crucial factors that critically influence the fibroblast phenotypes. The nanofiber-composite hydrogel capable of directional nanofiber alignment and tunable material composition can effectively induce a wide array of phenotypic plasticity in 3D cell culture.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-31)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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