https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/256 2026-07-03T22:01:01Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212297 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 https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212519 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 https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/213351 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 https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/210660 Title: Immunoregulatory protein-hybrid extracellular vesicles via self-loadable backbone cyclization for oral inflammatory bowel disease therapy Authors: Lee, Yeonju; Yoo, Chaerim; Kim, Kyung-Min; Kim, Sumin; Oh, Yu Kyung; Cho, Sookyung; Kim, Gil-Ran; Choi, Je-Min; Yang, Ji Yeong; Jung, Hyo-Il; Park, Sijin; Lee, Dong Yun; Kim, Young-Pil Abstract: Despite the potential of extracellular vesicles (EVs) and therapeutic proteins as carriers and cargos for oral delivery, their precise functional integration remains a persistent challenge, thereby limiting synergistic therapeutic outcomes. Here, we present a protein-hybrid, orally delivered EV strategy that integrates naturally bioactive EVs with self-loadable, backbone-cyclized immunoregulatory proteins for inflammatory bowel disease (IBD) therapy. Through computationally guided design and split intein-mediated backbone cyclization, we generated cyclized variants of key immunoregulatory proteins with improved functionality. Among these, C-R4-tagged cyclization of phosphatase domain of T-cell protein tyrosine phosphatase (ppTCPTP) improved membrane permeability, thermal stability, and anti-inflammatory activity. This backbone cyclization enabled efficient and high-capacity loading of ppTCPTP into native EVs that are not amenable to genetic engineering. Notably, these protein-hybrid EVs exhibited acidic resistance for oral delivery and synergistically enhanced antioxidant and anti-inflammatory effects in murine IBD organoids and in vivo colitis models, markedly reducing intestinal inflammation and restoring epithelial barrier integrity. Our findings highlight the translational potential of this self-loadable protein-EV platform as a safe and potent oral biologic for IBD therapy. 2026-04-01T00:00:00Z