Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Triphasic 3D In Vitro Model of Bone-Tendon-Muscle Interfaces to Study Their Regeneration.

The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model to study the regeneration of the bone-tendon-muscle interface. The 3D model was prepared from collagen and agarose, with different concentrations of hydroxyapatite to graduate the tissues from bones to muscles, resulting in a stiffness gradient. This graduated structure was fabricated using indirect 3D printing to provide biologically relevant surface topographies. MG-63, human dermal fibroblasts, and Sket.4U cells were found suitable cell models for bones, tendons, and muscles, respectively. The biphasic and triphasic hydrogels composing the 3D model were shown to be suitable for cell growth. Cells were co-cultured on the 3D model for over 21 days before assessing cell proliferation, metabolic activity, viability, cytotoxicity, tissue-specific markers, and matrix deposition to determine interface formations. The studies were conducted in a newly developed growth chamber that allowed cell communication while the cell culture media was compartmentalised. The 3D model promoted cell viability, tissue-specific marker expression, and new matrix deposition over 21 days, thereby showing promise for the development of new interfaces.

Current Advances on the Regeneration of Musculoskeletal Interfaces.

The regeneration of the musculoskeletal system has been widely investigated. There is now detailed knowledge about the organs composing this system. Research has also investigated the zones between individual tissues where physical, mechanical, and biochemical properties transition. However, the understanding of the regeneration of musculoskeletal interfaces is still lacking behind. Numerous disorders and injuries can degrade or damage tissue interfaces. Their inability to regenerate can delay the tissue repair and regeneration process, leading to graft instability, high morbidity, and pain. Moreover, the knowledge of the mechanism of tissue interface development is not complete. This review presents an overview of the most recent approaches of the regeneration of musculoskeletal interfaces, including the latest in vitro, preclinical, and clinical studies. Impact statement Interfaces between soft and hard tissues are ubiquitous within the body. These transition zones are crucial for joint motion, stabilisation and load transfer between tissues, but do not seem to regenerate well after injury or deterioration. The knowledge about their biology is vast, but little is known about their development. Various musculoskeletal disorders in combination with risk factors including aging and unhealthy lifestyle, can lead to local imbalances, misalignments, inflammation, pain and restricted mobility. Our manuscript reviews the current approaches taken to promote the regeneration of musculoskeletal interfaces through in vitro, pre-clinical and clinical studies.