The loss and leakage of transplanted cells at the target site represent the most critical bottlenecks hindering the clinical success of cell transplantation therapies. To address these profound challenges, biomaterial-based cell delivery systems have emerged as indispensable tools. This review provides a comprehensive overview of recent advancements in these delivery technologies, focusing primarily on platforms utilizing gelatin and collagen due to their exceptional biocompatibility, natural cell-adhesive motifs, and tunable properties. In particular, the authors have demonstrated a straightforward yet highly effective strategy to enhance cell retention and engraftment by optimizing the physical and rheological properties of crosslinked gelatin particles and hydrolyzed gelatin formulations. By precisely controlling parameters such as viscosity and particle size, these engineered gelatin matrices successfully suppress the physical backflow and leakage of injected cell suspensions immediately after administration. The utility and safety of this approach have been validated in challenging, specialized tissue environments, including the constantly beating myocardium and the extremely delicate subretinal space, offering a practical solution for medical practitioners without relying on complex or toxic in situ chemical crosslinking. Furthermore, this paper highlights cutting-edge clinical and translational applications where collagen-based carriers are precisely customized to match the unique mechanical and physiological environments of diverse target tissues. These examples include the use of temperature-responsive atelocollagen solutions for treating intractable fractures (nonunion), pH- and ion-responsive liquid collagen for severe knee osteoarthritis, and ultra-low-concentration soft hydrogels for spontaneous intracerebral hemorrhage. Each case underscores how tuning the collagen concentration, stiffness, and gelling mechanism is vital to withstand local tissue forces, prevent washout, or protect sensitive host structures. In conclusion, we discuss future perspectives on the critical importance of disease-specific material design. Rather than relying on a single, universal biomaterial, future regenerative therapies must adopt a tailored approach, selecting and engineering carriers based on the anatomical and mechanical demands of the target organ. This review emphasizes that such precise material tuning will be essential for unlocking the full therapeutic potential of next-generation cell-based medicines.

Hepatocyte sheet transplantation has attracted attention as a novel therapeutic strategy for intractable liver diseases. The authors have developed basic fibroblast growth factor (bFGF)-releasing nanoparticles designed to promote vascularization within transplanted tissues and thereby enhance engraftment efficiency. By utilizing these nanoparticles, transplantation of hepatocyte sheets was successfully achieved. This review outlines the design strategy of the bFGF-containing nanoparticles.

This review provides an overview of scaffold-based drug delivery systems (DDSs) designed to simultaneously achieve treatment and regeneration of diseased tissues. Conventional scaffolds for bone tissue engineering have primarily been developed as structural supports for space maintenance and tissue regeneration. While these materials are effective for relatively simple defects, their therapeutic capacity remains limited in complex pathological conditions accompanied by infection, inflammation, impaired blood supply, and abnormal bone metabolism. In contrast, scaffold-based DDSs represent a next-generation therapeutic platform in which the scaffold functions not only as a structural support but also as a localized delivery system for therapeutic agents. By incorporating and sustainably releasing antibodies, proteins, small-molecule drugs, and functional inorganic ions, these systems actively modulate the local pathological microenvironment and promote simultaneous tissue treatment and regeneration. This localized strategy enables high therapeutic concentrations at the target site while minimizing systemic exposure and adverse effects. A critical design concept of scaffold-based DDSs is multiscale structural control ranging from macro- to nano-scale architectures. Macroscale structures, such as interconnected pores and aligned channels, regulate cell infiltration, vascular invasion, and spatial guidance of newly formed tissues. Meanwhile, micro- and nanoscale surface structures strongly influence specific surface area, interfacial reactivity, adsorption capacity, and sustained release behavior of therapeutic agents. These hierarchical structural features also affect cell adhesion, differentiation, osteoclast activity, and tissue maturation, thereby integrating therapeutic and regenerative functions within a single biomaterial platform. Particular emphasis is placed on carbonate apatite-based honeycomb scaffolds developed by the authors as representative examples of scaffold-based DDSs. These include localized antibody DDSs using anti-sclerostin antibodies for osteoporotic bone defects, silver ion-based DDSs for antibacterial therapy, and copper ion-based DDSs for angiogenesis enhancement and the treatment of medication-related osteonecrosis of the jaw. These systems demonstrate the potential of scaffold-based DDSs as advanced therapeutic platforms capable of addressing complex pathological tissue defects in both dental and orthopedic fields. Finally, future perspectives are discussed regarding the design principles, clinical translation, and broader applications of scaffold-based DDSs for pathological tissue regeneration.

Recent advances in regenerative medicine and tissue engineering have accelerated interest in the development of vascularized three-dimensional (3D) tissue constructs that mimic the in vivo microenvironment. In particular, for thick tissues, vascular network formation and perfusion culture are essential to ensure adequate oxygen and nutrient supply. Perfusion culture not only enhances mass transport through continuous medium circulation but also promotes the maturation of vascular endothelial cells via fluid shear stress. In recent years, integration with microfluidic devices, 3D bioprinting, organoid technologies, and induced pluripotent stem cell (iPSC) technologies has enabled the construction of increasingly sophisticated vascularized tissues. Furthermore, the combination of artificial intelligence (AI), computational fluid dynamics (CFD) analysis, and Body-on-a-chip technologies is expected to expand applications in drug discovery and personalized medicine. This review summarizes recent advances in perfusion-based vascularized 3D tissue engineering technologies.

The gap between conventional in vitro 2D cultures and in vivo drug responses remains a major hurdle in drug discovery and clinical translation. To bridge the “missing link,” highly biomimetic 3D tissue models are emerging as promising platforms. These platforms are particularly critical for evaluating DDS, which must overcome significant physical barriers to reach target cells. This review first outlines cell sedimentation techniques, specifically the CAViTs and CMF methods, for simply constructing complex 3D tissues. We introduce their utility in general drug evaluation, including “patient-derived cancer avatar” models. Additionally, we briefly touch upon vascularized hepatic tissue models for assessing drug-induced vascular toxicity, and mature adipose tissue models for metabolic disease drug screening. Subsequently, we focus on how the 3D models are specifically applied to evaluate DDS, highlighting the integration of tissue engineering. The evolution of DDS evaluation models is illustrated through realistic physical barriers provided by highly hierarchical 3D tissue models. These models enable the visualization of differences in tissue penetrability depending on carrier sizes and shapes. Furthermore, we discuss the crucial role of recapitulating the 3D tumor microenvironment (TME) in evaluating next-generation DDS, such as antibody-drug conjugates (ADCs). The 3D cancer-stromal coculture models provide insights into how TME factors significantly influence ADC sensitivities, facilitating the elucidation of their TME-responsive pharmacological mechanisms. Moreover, the biomimetic systems serve as powerful platforms for screening novel combination partner compounds to synergistically enhance ADC efficacy. Finally, we discuss the future perspectives of establishing robust 3D tissue models. The fusion of tissue engineering and DDS evaluation technologies will accelerate drug development and strongly support the realization of functional precision medicine.

Organoid technology has attracted considerable attention as a next-generation alternative to animal models for drug discovery and disease modeling. However, conventional organoids are typically formed through self-organization under spatially uniform culture conditions, resulting in spherical tissues lacking defined polarity, lumen connectivity, and physiological transport pathways. Consequently, they cannot adequately reproduce in vivo pharmacokinetics such as absorption, distribution, metabolism, and excretion (ADME). In contrast, Organ-on-a-Chip (OoC) technologies enable precise fluidic control and tissue–tissue interactions, but most systems rely on two-dimensional cell cultures and fail to reproduce the three-dimensional architecture of native tissues. Therefore, integration of organoids with OoC systems is essential for constructing physiologically relevant in vitro models. Here, we present a modular engineering platform for controlling organoid morphology and integrating tissue modules into microfluidic devices. By spatially regulating cell positioning, extracellular matrix localization, and morphogen gradients, engineered organoids can be connected to fluidic networks for drug transport analysis. As a proof of concept, we constructed a blood–brain barrier (BBB)–brain tumor interconnected model and demonstrated enhanced vincristine transport and anti-tumor effects following P-glycoprotein inhibition. This approach provides a promising platform for evaluating brain-targeting therapeutics and drug delivery systems (DDS).

In the development of therapeutics for central nervous system (CNS) disorders, the blood-brain barrier (BBB) represents a major obstacle due to its stringent regulation of molecular transport into the brain. Therefore, establishing in vitro models that accurately recapitulate the structural integrity and selective permeability of the BBB is essential for advancing drug delivery strategies. In recent years, biomimetic systems known as BBB microphysiological systems (BBB-MPS) have attracted significant attention, as they enable the reconstruction of physiologically relevant BBB features, including cell-cell interactions and mechanical cues. This article provides an overview of current approaches for constructing BBB-MPS, including the selection of cell sources and the design of microfluidic devices. In addition, methods for evaluating model quality are discussed, focusing on key functional factors such as barrier integrity and transporter activity. The utility of BBB-MPS is demonstrated through applications in the study of neurodegenerative diseases, brain tumors, and infectious diseases. Finally, remaining challenges are addressed, particularly in terms of clinical predictivity and scalability for higher-throughput applications.

As a solution to various problems associated with injection needles, such as needle-stick injuries and fear of punctures, there is growing expectation for needle-free jet injectors. Our company has developed Actranza^Ⓡ Lab, a gas-powered jet injector that uses gunpowder for propulsion. This article presents the development history, the characteristics of the injector, and the immune effects through nucleic acid delivery.