One of the major obstacles to neural recovery following intracerebral hemorrhage (ICH) is the cavity-like lesion that occurs at the site of the hemorrhage, which impedes axonal regeneration. Here, we aim to address this challenge by investigating the migratory mechanisms of neural stem cells (NSCs) within the cavity in vitro using a hydrogel and endothelial cells. Mouse NSCs (mNSCs) isolated from the subventricular and subgranular zones using the 3D hydrogel culture were evaluated for their neurogenic, extracellular matrix (ECM), and adhesion-related mRNA expression compared to microglia (BV2) and secretory factors of human umbilical vein endothelial cells (HUVECs) in vitro and in vivo conditions. A hydrogel mesh combining mNSCs and HUVECs was developed for its therapeutic potential. mNSCs exhibit high stemness, neurogenesis, and ECM remodeling capabilities. mNSCs demonstrated close interaction with HUVECs and the surrounding vascular structures in in vitro and in vivo studies. Furthermore, mNSCs could degrade high concentrations of fibrin to facilitate migration and adhesion. mNSCs and HUVECs formed mesh networks through cell–cell contacts and maintained the structure through Matrigel support, potentially ensuring sufficient survival and regeneration capabilities. Our proposed hydrogel mesh platform with mNSCs and HUVECs demonstrated successful maintenance of cell survival and provision of structural support for the delivered cells by promoting ECM remodeling and neurogenesis, which may aid in axonal regeneration in the cavity lesions following ICH.

In this study, a multi breast cell-on-a-chip system was developed to recapitulate human-like breast cancer microenvironments by simultaneously co-culturing normal (MCF-10 A) and breast cancer cell lines (MCF-7 and MDA-MB-231) and to confirm the potential of plasma-activated PBS (P-PBS) containing various reactive oxygen species (ROS), as selective breast cancer remedial agent. The developed chip not only provided a 3D microenvironment supporting cell survival and interactions due to the use of gelatin as an extracellular matrix but also facilitated homogeneous growth and interactions between the different breast cell lines. Moreover, selective breast cancer apoptosis was investigated by real-time image analysis after treating cells with P-PBS on the developed chip; IC₅₀ values for MCF-7 and MDA-MB-231 were 390.50 and 600.75 μM, respectively. In addition, the breast cancer cell apoptosis pathway was found to be related to the ROS-activated intrinsic apoptosis pathway. The developed multi breast cells-on-a-chip platform could be used as a bio-platform that complements the limitations of existing in vitro models. The chip accurately reproduces cell-to-cell interactions by providing a tumor microenvironment based on the co-culture of heterogeneous cancer and normal cells and is expected to contribute meaningfully to breast cancer research and customized treatment development.

Irritant contact dermatitis (ICD) is a common inflammatory skin disease caused by direct exposure to exogenous irritants, characterized by skin barrier disruption and persistent inflammation. Here, we developed a 169-well hanging-drop platform for the uniform and scalable generation of human follicle dermal papilla cell (HFDPC)-derived organoids. The honeycomb-shaped microwell array promoted gravity-driven cellular aggregation and controlled organoid formation, while Matrigel provided an extracellular matrix (ECM)-rich three-dimensional (3D) microenvironment supporting tissue-like organization. Compared with conventional Matrigel-based culture, the proposed platform enabled improved control of organoid size and morphology, reproducible formation, and high-throughput production. The platform generated highly uniform organoids with a mean diameter of 116.55 ± 4.36 μm (mean ± SD) and a coefficient of variation of 3.74%, while integration with a standard 6-well plate enabled simultaneous production of up to 1014 organoids. In an ICD mouse model, transplantation of the organoids accelerated skin repair and alleviated inflammation, accompanied by reduced oxidative stress, restored SirT1 expression, attenuated PI3K/AKT phosphorylation, and suppressed Th1/Th17-mediated immune responses. These findings indicate that the combination of a 169-well hanging-drop architecture with a Matrigel-based 3D microenvironment provides a controlled and scalable platform for HFDPC organoid generation, with therapeutic potential demonstrated in an ICD mouse model.