Image-Guided Injectable Niche for Hepatocyte Transplantation

Abstract 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. Competing Interest Statement S.N.B. reports interests in Ropirio Therapeutics, Earli Inc., Sunbird Bio, Satellite Bio, Catalio Capital, Port Therapeutics, Matrisome Bio, Xilio Therapeutics, Ochre Bio, Impilo Therapeutics, Vertex Pharmaceuticals, Moderna, Johnson & Johnson, and Owlstone, which were not involved in this study. These interests are reviewed and managed under MIT policies for potential conflicts of interest. The authors declare that they have no other competing interests.