https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/257 2026-07-24T03:24:55Z 2026-07-24T03:24:55Z Kim, Eun Mi Ahn, Yujin Wang, Jason Hwang, Joanne Park, Junggeon Huang, Kai-Yu Kim, Seulgi Kim, Sujeong Dar, Roy D. Kim, Young Jun Shin, Heungsoo Lee, Chi Hwan Kong, Hyunjoon https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212297 2026-04-22T01:00:11Z 2026-08-01T00:00:00Z

Title: Matrix-guided embryo-like invasion enables 3D heart organoids with atrioventricular synchrony-like contraction Authors: Kim, Eun Mi; Ahn, Yujin; Wang, Jason; Hwang, Joanne; Park, Junggeon; Huang, Kai-Yu; Kim, Seulgi; Kim, Sujeong; Dar, Roy D.; Kim, Young Jun; Shin, Heungsoo; Lee, Chi Hwan; Kong, Hyunjoon Abstract: Engineering heart-like organoids in vitro holds significant promise for advancing cardiovascular research. While current approaches, such as suspended cell clusters in media or encapsulating them in gels, have shown potential, they are often challenged in generating organoids with defined chambers and synchronized contractions due to variations in outcomes linked to cell density. In this study, we present a strategy to modulate cell-cell interactions at a fixed cell density by mimicking bioprocesses underlying embryo implantation and invasion. Specifically, an embryoid body cultured on a collagen-poly(ethylene glycol) gel with greater porosity and hydrophilicity and lower stiffness than a pure collagen gel undergoes enhanced invasion and self-organization, resulting in functional, embryo-like cardiac organoids. These organoids exhibit distinct chamber structures surrounded by cardiac muscle, pacemaker cell innervation, atrioventricular synchrony-like contractions, recurring calcium flux, and electrocardiogram-like signals. Organoid development is associated with upregulated expression of mesodermal, ectodermal, and N-cadherin genes. This simple yet effective approach will enable robust modeling of heart physiology and drug response in vitro, offering valuable insights for translational cardiovascular research.

2026-08-01T00:00:00Z Lee, Sangmin Bae, SeongHeon Kwon, Hyunseok Seok, Ji Min Park, Su A Shin, Heungsoo https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/218687 2026-07-09T03:00:10Z 2026-08-01T00:00:00Z

Title: Harnessing inter-spheroid spacing and structural connectivity to direct collective cell migration and host vessel integration in 3D engineered tissue Authors: Lee, Sangmin; Bae, SeongHeon; Kwon, Hyunseok; Seok, Ji Min; Park, Su A; Shin, Heungsoo Abstract: Engineering functional vascular networks within three-dimensional (3D) tissues remains a major challenge in regenerative medicine. Here, we introduce a hybrid platform that integrates spheroids with gelatin methacryloyl (GelMA) hydrogels and 3D-printed poly(ε-caprolactone) (PCL) scaffolds to generate pre-vascularized 3D constructs. The scaffold architecture was designed with spatially defined chambers and interconnected pores incorporating catching strands that anchor spheroid positioning and direct cell migration from embedded spheroids. Additionally, the GelMA matrix establishes a permissive microenvironment conducive to cell adhesion and matrix remodeling, and the PCL framework preserves macroscopic structural integrity. Co-culture spheroids composed of human umbilical vein endothelial cells (HUVEC) and human adipose-derived stem cells (hADSC) enhanced sprouting and collective migration compared with suspended single cells, and also provided significant upregulation of extracellular matrix (ECM) remodeling genes and pro-angiogenic markers. Spatially distributed spheroids with 3D structure strongly modulated vascular network morphogenesis, whereby the inter-spheroid distance finely tuned cell migration dynamics and ECM remodeling. Scaffold microarchitecture further governed host tissue integration in vivo, with higher pore interconnectivity facilitating superior vascular infiltration and increased co-localization between host and engineered vessels. Notably, host vessels aligned preferentially along the inferior catching strands, suggesting geometry-associated vascular integration. Collectively, these findings demonstrate that precise spatial organization of spheroids combined with tailored 3D-printed scaffold architecture supports robust pre-vascularization of engineered tissues, offering a promising strategy for a variety of biomedical applications

2026-08-01T00:00:00Z Park, Eunji Lee, Eunjin Huh, Seung Jae Lee, Jinkyu Shin, Heungsoo https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212519 2026-05-09T05:01:17Z 2026-06-01T00:00:00Z

Title: Engineering cartilaginous constructs by integrating umbilical cord–derived mesenchymal stem cell spheroids and localized mineral ion delivery in 3D hydrogel Authors: Park, Eunji; Lee, Eunjin; Huh, Seung Jae; Lee, Jinkyu; Shin, Heungsoo Abstract: The engineering three-dimensional (3D) cartilage tissue from mesenchymal stem cells is often obstructed by diffusion limitations, uncontrolled signal delivery, and hypertrophic differentiation following chondrogenesis. We herein report a 3D cartilaginous construct by encapsulation of spheroids of human umbilical cord–derived MSCs (hUCSCs) within in Gelatin methacryloyl hydrogels where the mineral–coated fibers (MFs) were integrated within the spheroid for localized ion delivery, thereby alleviating diffusion limitations. Through the intrinsic properties of hUCSCs, this system achieved robust chondrogenesis while minimizing hypertrophic progression. MFs led to a greater than threefold upregulation in chondrogenic gene expression and enhanced deposition of chondrogenic extracellular matrix in hUCSC spheroids, without concomitant increases in hypertrophic markers or matrix components. Comparative analysis revealed that hUCSCs exhibited superior chondrogenic potential and reduced hypertrophic gene expression relative to human bone marrow–derived MSCs. These findings highlight the potential of the MFs–incorporated composite spheroids–laden hydrogels as a novel biomimetic strategy for stable cartilage biofabrication, as they selectively promote hUCSC chondrogenic differentiation while mitigating hypertrophic maturation in a controlled 3D microenvironment.

2026-06-01T00:00:00Z Li, Xiaohui Duan, Shanzhou Yang, Jiandong Piao, Chunxian Zhou, Yang Ge, Chenglong Liang, Qiujun Lee, Minhyung Yin, Lichen Chen, Yongbing https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/213351 2026-06-18T01:30:27Z 2026-06-01T00:00:00Z

Title: Inflammation-responsive hierarchical delivery of anti-inflammatory siRNA and peptide alleviates cytokine storm in pneumonia Authors: Li, Xiaohui; Duan, Shanzhou; Yang, Jiandong; Piao, Chunxian; Zhou, Yang; Ge, Chenglong; Liang, Qiujun; Lee, Minhyung; Yin, Lichen; Chen, Yongbing Abstract: Pulmonary delivery of anti-inflammatory siRNA holds great potential for the management of severe pneumonia. However, conventional siRNA carriers, primarily cationic polymers, struggle to penetrate the mucus barrier, resulting in limited transfection efficiency. Herein, nanocomplexes (NCs) capable of penetrating both the mucus and cytomembrane barriers were developed to deliver TNF-alpha siRNA (siTNF-alpha) for effective pneumonia management. To construct the NCs, membrane-penetrating polypeptide (DPP) first condensed siTNF-alpha and formed a cationic inner core, which was further coated with a charge-reversal polymer (PD) followed by the adsorption of a RAGE-binding peptide (RBP) via electrostatic interactions. The resulting RDDsT NCs exhibited negatively charged surfaces and thus enabled efficient mucus layer penetration after intratracheal administration in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice. In the slightly acidic microenvironment of inflamed alveolar space, PD underwent charge reversal from negatively charged to positively charged, shedding off to facilitate the intracellular delivery of the DPP/siTNF-alpha core into alveolar macrophages. Meanwhile, the liberated RBP blocked RAGE-ligand interactions, further down-regulating pro-inflammatory factors. Consequently, the cooperative action of siTNF-alpha and RBP alleviated inflammation and propelled the recovery of pulmonary functions. This study renders an enlightened strategy to overcome the mucus/cytomembrane barrier against pulmonary siRNA delivery, and holds profound potential for gene/peptide co-therapy against pneumonia.

2026-06-01T00:00:00Z