Periodic Reporting for period 1 - UNIINK (Universal 3D printer bioink for Type 1 diabetes cell therapy)
Reporting period: 2024-01-01 to 2025-06-30
Type 1 Diabetes Mellitus (T1DM) is a major global health concern, particularly affecting children, where it represents 5–10% of all diabetes cases. T1DM is characterized by an autoimmune-mediated destruction of pancreatic β-cells, resulting in absolute insulin deficiency. Patients depend on lifelong exogenous insulin therapy and must continually monitor their blood glucose to prevent serious complications such as nephropathy, retinopathy, disability, and premature death. Despite advancements, including novel insulin formulations and automated insulin delivery systems, current treatments cannot truly replicate the physiological insulin secretion of healthy β-cells. As a result, full glycaemic control remains challenging, and patients remain at risk of acute and chronic complications, including life-threatening episodes of hypoglycaemia.
Restoration of endogenous pancreatic function can be achieved in a minority of cases through whole pancreas or islet transplantation. However, these approaches are limited by severe hurdles: scarcity of donor organs, variable post-transplant engraftment, hypoxia-induced cell loss, and significant surgical risks. Furthermore, chronic immunosuppression is required to prevent graft rejection, exposing patients to significant long-term risks, even as anti-inflammatory regimens improve.
Our innovative platform, UNIINK, addresses these unmet needs in cell therapy for T1DM. UNIINK enables rapid, sterile, and operator-independent fabrication of 3D bioprinted micro-spheroids—up to 80 spheroids per minute, each containing up to 3 million B cells, allowing normoglycemia restoration in T1DM patients.
Restoration of endogenous pancreatic function can be achieved in a minority of cases through whole pancreas or islet transplantation. However, these approaches are limited by severe hurdles: scarcity of donor organs, variable post-transplant engraftment, hypoxia-induced cell loss, and significant surgical risks. Furthermore, chronic immunosuppression is required to prevent graft rejection, exposing patients to significant long-term risks, even as anti-inflammatory regimens improve.
Our innovative platform, UNIINK, addresses these unmet needs in cell therapy for T1DM. UNIINK enables rapid, sterile, and operator-independent fabrication of 3D bioprinted micro-spheroids—up to 80 spheroids per minute, each containing up to 3 million B cells, allowing normoglycemia restoration in T1DM patients.
During the project, we successfully produced spheroids composed of collagen-I crosslinked with tannic acid (ColTA) and demonstrated their long-term viability and functionality in vitro, maintaining β-cell survival and insulin secretion capacity for up to two months. These results validate the structural and biochemical suitability of our ColTA matrix to support 3D cell culture and endocrine function over extended periods.
In vivo studies further confirmed the translational potential of our technology. Spheroid transplantation into immunocompetent mice enabled the retrieval of intact spheroids without eliciting inflammatory or fibrotic responses, as demonstrated through cytokine profiling and flow cytometry analyses. These results suggest that the biomaterial composition confers a degree of immune invisibility, supporting its use without systemic immunosuppression.
To assess therapeutic efficacy, we tested the UNIINK-fabricated spheroids in different murine models of diabetes. Notably, transplantation of INS1-E β-cell–laden spheroids into both streptozotocin-induced hyperglycemic mice and spontaneous autoimmune diabetic NOD mice led to substantial and sustained reductions in blood glucose levels. In treated animals, glycaemia decreased from severely hyperglycemic levels (>600 mg/dL) to near-physiological values (200–300 mg/dL), indicating a functional endocrine response and metabolic correction.
These promising results highlight the robustness, biofunctionality, and immunomodulatory properties of our UNIINK platform and support its further development toward clinical translation in T1DM therapy.
On the other hand, to support the future commercialization of our product and the creation of a UNIINK-based spin-off, it was essential to us to find a suitable protocol to preserve our 3D models for storage, transport, and ready-to-use applications. Off-the-shelf availability improves accessibility, scalability, and standardization, enabling clinical translation, collaborative research, and commercial deployment. In this project, we conducted a preliminary evaluation of different cryopreservation strategies for ColTA microspheres encapsulating INS1E cells Our preliminary cryopreservation protocol has demonstrated to maintain both the viability and insulin-secreting function of β-cells encapsulated in ColTA spheroids after freezing and thawing. It was confirmed by live/dead viability assays and robust responses in glucose-stimulated insulin secretion (GSIS) tests.
In vivo studies further confirmed the translational potential of our technology. Spheroid transplantation into immunocompetent mice enabled the retrieval of intact spheroids without eliciting inflammatory or fibrotic responses, as demonstrated through cytokine profiling and flow cytometry analyses. These results suggest that the biomaterial composition confers a degree of immune invisibility, supporting its use without systemic immunosuppression.
To assess therapeutic efficacy, we tested the UNIINK-fabricated spheroids in different murine models of diabetes. Notably, transplantation of INS1-E β-cell–laden spheroids into both streptozotocin-induced hyperglycemic mice and spontaneous autoimmune diabetic NOD mice led to substantial and sustained reductions in blood glucose levels. In treated animals, glycaemia decreased from severely hyperglycemic levels (>600 mg/dL) to near-physiological values (200–300 mg/dL), indicating a functional endocrine response and metabolic correction.
These promising results highlight the robustness, biofunctionality, and immunomodulatory properties of our UNIINK platform and support its further development toward clinical translation in T1DM therapy.
On the other hand, to support the future commercialization of our product and the creation of a UNIINK-based spin-off, it was essential to us to find a suitable protocol to preserve our 3D models for storage, transport, and ready-to-use applications. Off-the-shelf availability improves accessibility, scalability, and standardization, enabling clinical translation, collaborative research, and commercial deployment. In this project, we conducted a preliminary evaluation of different cryopreservation strategies for ColTA microspheres encapsulating INS1E cells Our preliminary cryopreservation protocol has demonstrated to maintain both the viability and insulin-secreting function of β-cells encapsulated in ColTA spheroids after freezing and thawing. It was confirmed by live/dead viability assays and robust responses in glucose-stimulated insulin secretion (GSIS) tests.
With the results obtained in this project we have made significant progress toward our objectives. In parallel, we have established a collaboration between our institution (IBEC) and Vall d’Hebrón Hospital and VHIR (Vall d’Hebrón Institut de Recerca).
For near future we aim on doing future research with UNIINK technology and human pancreatic β-cells (both cell lines and primary cells, commercially available and donor-derived). Once efficacy is demonstrated, we’re going to finish all the preclinical testing required to initiate the clinical trial. In addition, the creation of a future spin off is one of our priorities, improving our business case and the regulatory roadmap.
To this end, a business plan was subcontracted to Catalyze Group a market consultancy company specialized in healthcare ventures. A consolidated business model will be obtained, and a business model canvas will be developed to ensure the product meets the real needs of the patients and that the spin-off will offer this solution in a sustainable market.
The potential of our results will not be limited only to patients but also society in general including the cell therapy industry through pharmaceutical companies expanding their therapeutic portfolios and hospitals that would like to initiate non-industrial fabrication of advanced therapy medicinal products (ATMPs).
Although Spain and Catalonia have active policies regarding cell therapy adoption and integration into the National Health System there still is a need for standardisation of regulatory frameworks with the aim of facilitating patient access to these novel therapies, improving their health outcomes while offering solutions to underserved populations who currently have limited treatment options. ATMPs still remain relatively new and an unexplored territory in many parts of Europe and the rest of the world, with a significant path ahead towards the standardisation of reimbursement models, hospital enabling infrastructures and broader clinical adoption.
For near future we aim on doing future research with UNIINK technology and human pancreatic β-cells (both cell lines and primary cells, commercially available and donor-derived). Once efficacy is demonstrated, we’re going to finish all the preclinical testing required to initiate the clinical trial. In addition, the creation of a future spin off is one of our priorities, improving our business case and the regulatory roadmap.
To this end, a business plan was subcontracted to Catalyze Group a market consultancy company specialized in healthcare ventures. A consolidated business model will be obtained, and a business model canvas will be developed to ensure the product meets the real needs of the patients and that the spin-off will offer this solution in a sustainable market.
The potential of our results will not be limited only to patients but also society in general including the cell therapy industry through pharmaceutical companies expanding their therapeutic portfolios and hospitals that would like to initiate non-industrial fabrication of advanced therapy medicinal products (ATMPs).
Although Spain and Catalonia have active policies regarding cell therapy adoption and integration into the National Health System there still is a need for standardisation of regulatory frameworks with the aim of facilitating patient access to these novel therapies, improving their health outcomes while offering solutions to underserved populations who currently have limited treatment options. ATMPs still remain relatively new and an unexplored territory in many parts of Europe and the rest of the world, with a significant path ahead towards the standardisation of reimbursement models, hospital enabling infrastructures and broader clinical adoption.