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한양대학교

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Bioact. Mater., Available online 18 February 2025 | https://doi.org/10.1016/j.bioactmat.2025.02.024 Biomimetic integration of functionally controlled modular tissue building blocks for engineering 3D vascularized adipose tissue

Sangmin Lee ^a,b,c, Jeongbok Lee^a,d, Hyunseok Kwon ^a,d, Heungsoo Shin^a,d,e

^aDepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
^bDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA
^cDepartment of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA
^dEducation and Research Group for Biopharmaceutical Innovation, Hanyang University, Republic of Korea
^eInstitute of Nano Science and Technology, Hanyang University, Republic of Korea

Corresponding author : Heungsoo Shin

Abstract

Adipose tissue is highly vascularized, which is crucial for homeostasis and energy storage. Current efforts to engineer 3D vascularized adipose tissue in vitro typically involve co-culturing adipocytes and endothelial cells, but adipogenic differentiation often suppresses endothelial function. In this study, we propose a novel approach to reconstruct vascularized adipose tissues in vitro by effectively coupling adipogenesis and vasculogenesis. First, we developed adipo-inductive nanofibers (ID/F@INS) that contain indomethacin and insulin. The in vitro adipogenesis of human adipose-derived stem cells (hADSCs) in general medium was significantly enhanced in adipogenic spheroids (AS) prepared with hADSCs and ID/F@INS, which were encapsulated in a gelatin methacryloyl (GelMA) hydrogel. To further replicate clustering during de novo adipogenesis, we generated AS of varying sizes and found that larger spheroids exhibited markedly greater adipogenesis than smaller ones. At the same time, we used hADSCs and human umbilical vein endothelial cells to generate vascular spheroids (VS). The biomimetic integration of AS and VS within GelMA hydrogels enabled us to investigate the interactions between de novo adipogenesis and vascularization. The integration of the two types of spheroids (VS:AS ratio of 2:1) significantly improved vascular network formation, indicating the concurrent stimulation of adipogenesis and vasculogenesis. This system was then applied to develop an in vitro obesity-like white adipose dysfunction model characterized by reduced vascularization and the elevated expression of pro-inflammatory cytokines. In addition, we found both vascularization and adipogenesis in vivo when we implanted the engineered tissue into mice, demonstrating the potential of our tissue for therapeutic applications in tissue reconstruction.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-03-07)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생물공학

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