Image-Guided Injectable Niche for Hepatocyte Transplantation.

Liver transplantation remains the standard of care for end-stage liver failure, yet it is constrained by donor scarcity, surgical complexity, and restricted access for many patients. Cell-based therapies offer a potential alternative, yet their translation has been hindered by low engraftment, poor localization, and a lack of delivery strategies that are both effective and minimally invasive. To address these challenges, we developed a new approach termed INSITE (Injected Self-assembled Image-guided Tissue Ensembles), an injectable platform composed of primary human hepatocytes and hydrogel microspheres that can be delivered by image-guided injection and assembled in situ into supportive, vascularizable scaffolds. In vivo, ultrasound-guided delivery into an ectopic site enabled precise graft localization, persistent visibility under noninvasive imaging, and vascular integration. Hepatocytes within these niches remained confined to the scaffold and maintained long-term functional activity. Furthermore, tuning material properties allowed control over scaffold remodeling and vascular recruitment, providing a means to enhance graft function. By integrating image-guided delivery with a modular and supportive scaffold, INSITE establishes a clinically compatible strategy for advancing minimally invasive cell therapies.