Bose, Suman

ABSTRACT Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the intestine’s integrated vascular, immune, and metabolic complexity. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37°C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

Autoimmune diseases arise from a breakdown of immune tolerance and complex interplay of genetic susceptibility, environmental triggers, tissue-specific immune responses, microbiota, and regulatory pathways. Mouse models remain essential for dissecting these mechanisms, but no single model fully reproduces the heterogeneity, chronicity, and immune complexity of autoimmune disease in humans. This review summarizes classical murine and humanized mouse models used to study inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), and rheumatoid arthritis (RA). We also highlight disease-specific scoring systems, including clinical indices, histopathology, imaging, cytokine profiling, autoantibody assessment, and human immune-cell readouts, as essential tools for standardized interpretation. Conventional murine models provide experimental control and mechanistic clarity, whereas humanized models improve assessment of human immune responses, patient-specific biology, and therapeutic translation. However, humanized systems remain limited by incomplete immune reconstitution, graft-versus-host disease, donor variability, cost, and incomplete tissue architecture. By providing a comparative framework spanning both conventional and humanized models, this review aims to guide informed model selection tailored to specific research questions in autoimmune disease biology and translational therapeutic development.

Abstract Foreign body response is a common yet serious challenge for biomedical implants. It can trigger inflammation and eventually lead to the formation of a fibrotic capsule, which compromises device function. Although significant efforts have been made to develop antifibrotic surface coatings for implantable materials, developing broadly applicable solutions remains challenging due to the diversity of materials used in biomedical implants. Here, we propose a simple and versatile strategy to develop antifibrotic coatings for biomedical implants. Photoreactive benzophenone groups are incorporated into designer polymers to enable covalent attachment to various substrates. The effect of benzophenone group density within polymer chains on surface coating efficiency was investigated, and an optimal BP incorporation ratio was identified. Polymers incorporating varying ratios of an anti-fibrotic small molecule and anti-fouling zwitterionic moieties were synthesized and successfully attached to silicone implants. In vivo evaluation of these implants in C57BL/6 mice identified an optimized polymer composition that reduced fibrotic capsule thickness by around 60%. Coating of commercial medical catheters with this optimized polymer reduced collagen deposition by over 3.5-fold following 4 weeks of implantation in the peritoneal space of C57BL/6 mice. Finally, we demonstrated that the optimized polymer coating can be readily applied to a variety of commonly used biomedical materials using this straightforward method, highlighting the versatility of the approach. This work provides a facile and broadly applicable strategy for developing antifibrotic coatings, which has the potential to expand the design of surface modifications aimed at improving the performance of biomedical implants.

Abstract Immune reactions to medical implants often lead to encapsulation by fibrotic tissue and impaired device function. This process is thought to initiate by protein adsorption, which enables immune cells to attach and mount an inflammatory response. Previously, several antifibrotic materials have been either designed to reduce protein adsorption or discovered via high‐throughput screens (HTS) to favorably regulate inflammation. The present work introduces antifouling immunomodulatory (AIM) copolymer coatings, which combine both strategies to effectively enhance implant protection. AIM copolymers synergistically integrate zwitterionic moieties to resist protein fouling, HTS‐derived antifibrotics for immunomodulation, and silane monomers for grafting to diverse substrates including elastomers, ceramics, and metals. Interestingly, simply combining these monomers into conventional random or block copolymer architectures yielded no significant advantage over homopolymers. By contrast, an unusual polymer chain architecture — a zwitterionic block flanked by a mixed zwitterionic immunomodulatory segment — showed superior fibrosis resistance in both peritoneal and subcutaneous sites over one month in immunocompetent mice. This architecture also improved the performance of two different HTS‐derived antifibrotic monomers, suggesting that tailoring AIM architectures may broadly complement immunomodulatory chemistries and provide a versatile approach to improving implant longevity.

The transplantation of engineered cells that secrete therapeutic proteins presents a promising method for addressing a range of chronic diseases. However, hydrogels used to encase and protect non-autologous cells from immune rejection often suffer from poor mechanical properties, insufficient oxygenation, and fibrotic encapsulation. Here, we introduce a composite encapsulation system comprising an oxygen-permeable silicone cryogel skeleton, a hydrogel matrix, and a fibrosis-resistant polymer coating. Cryogel skeletons enhance the fracture toughness of conventional alginate hydrogels by 23-fold and oxygen diffusion by 2.8-fold, effectively mitigating both implant fracture and hypoxia of encapsulated cells. Composite implants containing xenogeneic cells engineered to secrete erythropoietin significantly outperform unsupported alginate implants in therapeutic delivery over 8 weeks in immunocompetent mice. By improving mechanical resiliency and sustaining denser cell populations, silicone cryogel skeletons enable more durable and miniaturized therapeutic implants.