Background/Objectives: Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by the destruction of pancreatic β-cells, leading to insulin deficiency. Current therapies, such as islet transplantation, face significant challenges, including limited donor availability and the need for lifelong immunosuppression. Encapsulation technologies offer a promising alternative, providing immune protection and maintaining β-cell viability. In this study, we propose an encapsulation device featuring a spiral tubular semipermeable polyethersulfone (PES) membrane reinforced with a rigid biocompatible resin scaffold. Methods: The PES membrane was engineered with a tailored porosity of 0.5 µm, enabling efficient nutrient and oxygen exchange while preventing immune cell infiltration. Using INS-1E insulin-secreting cells aggregated into size-controlled islet-like spheroids (ILSs), we evaluated the device’s performance. Results: The device achieved high ILS viability and insulin secretion over 48 h at therapeutic densities, maintaining functionality comparable to free-floating ILSs (control). The PES membrane, with its mechanical stability and biocompatibility, ensured durability without compromising diffusion dynamics, overcoming a critical limitation of other encapsulation approaches. Importantly, the device geometry allowed for the encapsulation of up to 356,000 islet equivalents (IEQs) in a single capillary fiber, reaching therapeutic thresholds for T1D patients. Conclusions: this device, with its innovative design, enables high-density encapsulation while preserving ILS functionality and scalability, making it a potential platform for clinical application. This work highlights the potential of PES-based encapsulation devices to overcome key barriers in T1D treatment, paving the way for personalized, long-term solutions to restore insulin independence.

Cardiovascular diseases remain the leading cause of mortality in developed countries. Among these conditions, acute myocardial infarction (AMI) is associated with particularly high rates of cardiac morbidity and mortality. Cardiac development in mammals is primarily dependent on cardiomyocyte (CM) proliferation during embryonic and early postnatal stages. However, following birth, the proliferative capacity of CMs declines markedly, with only limited cellular renewal occurring during adult life in response to pathological injury. Consequently, the irreversible loss of functional cardiomyocytes and the subsequent formation of fibrotic scar tissue frequently lead to persistent cardiac dysfunction and progressive impairment of cardiac physiology. Cardiomyocyte self-renewal is a tightly regulated process involving multiple molecular pathways. Among factors implicated in this regulation, microRNAs (miRNAs) have emerged as key modulators coordinating both cardiac development and tissue repair mechanisms. In this context, extracellular vesicles (EVs) have attracted considerable interest as potential modulators of these regenerative processes. In particular, mesenchymal stromal cells (MSCs) represent a promising therapeutic platform due to their immunomodulatory and anti-fibrotic properties demonstrated across multiple in vitro and in vivo models. Furthermore, the therapeutic potential of MSC-derived EVs can be enhanced through bioengineering approaches aimed at improving targeted molecular delivery. In this review, we summarize recent advances in the development and application of EV-based therapeutic strategies, with particular emphasis on their potential use as advanced therapy medicinal products (ATMPs) for cardiovascular regeneration and repair.

Hepatic ischemia-reperfusion injury (IRI) is one of the main clinical challenges in liver surgery and transplantation, contributing to postoperative complications and graft dys-function. The pathogenesis of hepatic IRI is complex and multifactorial, involving meta-bolic consequences induced by ischemia, oxidative stress, inflammatory responses, endo-thelial dysfunction, and the activation of immune pathways upon reperfusion. Despite extensive research efforts, the translation of preclinical findings into effective clinical in-terventions has been limited. This review provides a critical overview of the most im-portant models employed to investigate hepatic IRI. Conventional two-dimensional (2D) in vitro systems, including monocultures and co-culture models, offer controlled envi-ronments for mechanistic studies and high-throughput screening but fail to fully repro-duce the structural and cellular complexity of the liver microenvironment. Animal mod-els, particularly those based on mice, rats, and pigs, remain essential for studying the sys-temic and multicellular aspects of hepatic IRI. However, species-specific physiological differences, ethical concerns, high costs, and limited translational predictability represent significant limitations. In this context, three-dimensional (3D) liver models have emerged as promising alternatives able to bridge the gap between in vitro systems and animal ex-perimentation. By better recapitulating tissue architecture, cell-cell interactions, and func-tional heterogeneity, 3D platforms offer improved physiological relevance and transla-tional potential. In detail, we discuss the strengths and limitations of each experimental approach and highlight the role of advanced 3D models as complementary tools that may facilitate more accurate investigations of hepatic IRI and accelerate the development of therapeutic strategies.

Hepatic ischemia–reperfusion injury (IRI) is a major clinical challenge in liver surgery and transplantation, contributing to postoperative complications and graft dysfunction. The pathogenesis of hepatic IRI is complex and multifactorial, involving ischemia-induced metabolic consequences, oxidative stress, inflammatory responses, endothelial dysfunction, and the activation of immune pathways upon reperfusion. Despite extensive research efforts, the translation of preclinical findings into effective clinical interventions remains limited. This review provides a critical overview of the principal models used to investigate hepatic IRI. Conventional two-dimensional in vitro systems, including monoculture and co-culture models, offer controlled environments for mechanistic studies and high-throughput screening, but fail to fully reproduce the structural and cellular complexity of the liver microenvironment. Animal models, particularly those based on mice, rats, and pigs, remain essential for studying the systemic and multicellular aspects of hepatic IRI. Nevertheless, species-specific physiological differences, ethical concerns, high costs, and limited translational predictability represent significant limitations. In this context, three-dimensional liver models have emerged as promising alternatives capable of bridging the gap between in vitro systems and animal experimentation. By more accurately recapitulating tissue architecture, cell–cell interactions, and functional heterogeneity, 3D platforms offer enhanced physiological relevance and translational potential. We discuss the strengths and limitations of each experimental approach and highlight the role of advanced 3D models as complementary tools that may enable more accurate investigations of hepatic IRI and accelerate the development of effective therapeutic strategies.