Biomaterials for cell delivery

Abstract

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.