Elisa Balboni, Jocelyn Nikita Campa-Carranza, Tommaso Bo, Gabrielle E. Rome, Henry Seaborne, Arya Venugopalan, Rim Ouni, Jesus Paez-Mayorga, Corrine Ying Xuan Chua, Alessandro Grattoni
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Abstract
Pancreatic islet transplantation represents a promising therapeutic strategy for type 1 diabetes (T1D). In this context, the subcutaneous space offers a safer and more accessible alternative to the clinically established intraportal delivery route. However, a major unmet need remains the development of a site capable of supporting rapid vascularization and sustained islet function. In its current configuration, this approach is limited by poor vascularization, hypoxia-driven islet loss, loss of spatial control during graft delivery, and tissue disruption associated with delivery strategies. To address these challenges, the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device provides a prevascularized subcutaneous platform that supports islet viability and enables localized immunosuppressant delivery. In this study, we describe the incorporation of a 3D-printed removable placeholder into the NICHE platform to preserve a defined cavity within the device during prevascularization and enable subsequent islet delivery. The placeholder shapes the spatial organization of vascularized tissue, promoting uniform three-dimensional islet distribution upon transplantation. Surface characterization showed that polyamide and BioMed Clear resin exhibit distinct cell adhesion properties, enabling controlled tissue integration and atraumatic placeholder removal. Collectively, these results are consistent with preservation of vascularization, improved islet dispersion within the cell reservoir, reduced inflammatory cell infiltration, and support of metabolic function compared to injection-based delivery. These findings establish spatially controlled cell delivery within a prevascularized niche as a key design principle for enhancing engraftment efficiency and advancing the translational potential of subcutaneous islet transplantation for T1D and related cell-based therapies.
Graphical abstract
The alternative text for this image may have been generated using AI.
期刊介绍：
Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology.
General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules.
Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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