Current Opinion in Biomedical Engineering最新文献

Age related macular degeneration and other retinal degenerative disorders are characterized by disruption of the outer blood retinal barrier (oBRB) with subsequent ischemia, neovascularization, and atrophy. Despite the treatment advances, there remains no curative therapy, and no treatment targeted at regenerating native-like tissue for patients with late stages of the disease. Here we present advances in tissue engineering, focusing on bioprinting methods of generating tissue allowing for safe and reliable production of oBRB as well as tissue reprogramming with induced pluripotent stem cells for transplantation. We compare these approaches to organ-on-a-chip models for studying the dynamic nature of physiologic conditions. Highlighted within this review are studies that employ good manufacturing practices and use clinical grade methods that minimize potential risk to patients. Lastly, we illustrate recent clinical applications demonstrating both safety and efficacy for direct patient use. These advances provide an avenue for drug discovery and ultimately transplantation.

Regenerative rehabilitation is a promising field aimed at harnessing the regenerative potential of stem-cell therapeutics to maximize functional recovery. Here, we outline recent advancements in the field of regenerative rehabilitation for treating knee osteoarthritis (KOA) and we highlight sex-specific considerations to promote knowledge translation to the clinic. A systematic review suggests that sexual dimorphism in the efficacy of regenerative rehabilitation approaches for the treatment of KOA may be partly attributed to the functional decline of female mesenchymal stem cells (MSCs) over the lifespan, particularly after menopause. These declines are likely to be accompanied by poor clinical outcomes. While evidence is far from adequate, physical therapeutics have emerged as a means to promote estrogen signaling in MSCs, potentially reversing menopause-related MSC dysfunction. This study calls for actions to dissect the effects of menopause, together with physical therapeutics, on stem-cell therapeutics toward the development of effective regenerative rehabilitation approaches.

The myotendinous junction (MTJ) acts as a bridge between muscle and tendon; yet its high stiffness relative to muscle fibers renders the tissue susceptible to injuries due to eccentric loading disparities. The limited regenerative capacity of MTJ tissue and potential for postsurgical scarring and reinjury necessitates complementary therapeutics that can enhance cellular interactions, restore mechanical properties, and support tissue rehabilitation.

This review explores various approaches to engineer the MTJ utilizing biomaterial scaffolds and cellularized materials that mimic structure and function. While biomimetic materials show promise, challenges remain due to the interface's complexity and differing patient- and location-specific structure–function characteristics, necessitating further research to address these gaps. This review also highlights the importance of studying MTJ injuries in women's health and craniofacial reconstruction. Furthermore, engineered MTJ models provide versatile platforms for investigating trauma and degeneration, thus offering potential for advancing research across multiple fields, shedding light on interactions at tissue interfaces, and shaping the future of MTJ rehabilitation.

Organ on a chip, or in the context of liver, liver-on-a-chip or LoC, are recently in the lookout for being bioengineered tools preserving the in vivo cell features and recapitulating the complexity of liver physiology in a controlled microfluidic environment. In the recent years, LoC have been tailored at several levels including biological input, matrix and mechanobiological cues or additional design features such as patterned cultures, multi-organ chips or sensor integration. Latest research in LoC designs include the integration of mechanobiological cues and recapitulation of the most common liver disease etiologies (alcohol associated liver disease, MAFLD or viral infection), enhancing LoC value for hepatotoxicity testing, drug discovery and research. Liver regeneration is a common physiological response to diverse injuries to the liver. In this review, we summarize the latest findings learned from LoC to understand liver regeneration, focusing on the role of transcription growth factor beta (TGFβ), hepatocyte growth factor (HGF) and hypoxia inducible factor 1 alpha (HIF-1α) as key players in the regenerative response by regulating fibrosis, EMT, proliferation and inflammation among others.

Recent years have seen considerable rise in the cases of non-alcoholic and alcohol-associated/related liver disease. Though largely a reversible condition in early stages, if left untreated, it leads to permanent damage in the form of fibrosis to cirrhosis to liver cancer. Early identification of the stage of progression can arrest chronic liver disease (CLD). Development of in vitro systems that mimic the patient's liver allows research on liver regeneration and CLD. At cellular and tissue level, the omics expression profiles provide a valid tool to analyze and compare between the in vitro developed and in vivo liver. Here, in a systematic way, we review the recent publications on single to multiple gene expression profiling of metabolic dysfunction-associated steatotic liver disease (MASLD) (previously included conditions of Non-Alcoholic Fatty Liver Disease, NAFLD) to identify the potential pharmacologically important biomarker.

Bioprinted liver organoids (LOs) have emerged as a crucial tool for investigating patient-specific models and enhancing disease comprehension as well as overall patient care. These systems are comprised of liver-specific cell types along with suitable biomaterials to facilitate the printing process and provide a microenvironment for cell accommodation. Various printing technologies, such as jetting, extrusion, and stereolithography, each present distinct advantages and disadvantages concerning printing resolution, rheological properties, and biomaterial selection. Leveraging patient-derived cells, these models facilitate the development of personalized in vitro liver models, enabling the exploration of disease progression and drug efficacy. Advancing research on liver tissue-specific printable biomaterials and exploring designs that can effectively mimic the diverse functions of liver tissue will greatly expedite clinically relevant model development and augment patient care.

Liver cell therapy presents a promising alternative to liver transplantation for patients with liver failure and hereditary liver diseases. However, its clinical implementation is limited largely due to the scarcity of human hepatocytes. Here, we review strategies to generate functional human hepatocytes with a mature phenotype and liver repopulation capability and highlight their potential clinical applications in hepatocyte transplantation and bioartificial liver transplantation. We summarize new delivery methods to improve hepatocyte engraftment, such as patch grafting and ectopic transplantation, and discuss potential future directions.

Environmental exposure of arsenic impairs the cardiometabolic profile, skeletal muscle health, and neurological function. Such declining tissue health is observed as early as in one's childhood, where the exposure is prevalent, thereby accelerating the effect of time's arrow. Despite the known deleterious effects of arsenic exposure, there is a paucity of specific treatment plans for restoring tissue function in exposed individuals. In this review, we propose to harness the untapped potential of existing regenerative rehabilitation programs, such as stem cell therapeutics with rehabilitation, acellular therapeutics, and artificial intelligence/robotics technologies, to address this critical gap in environmental toxicology. With regenerative rehabilitation techniques showing promise in other injury paradigms, fostering collaboration between these scientific realms offers an effective means of mitigating the detrimental effects of arsenic on tissue function.

The mechanical environment plays an important role in influencing cell identity. The nucleus's organization and mechanical state are essential regulators of cellular function. However, open questions remain about the mechanisms underlying how the physical microenvironment influences nuclear mechanics and organization to drive specific transcriptional and epigenetic shifts. Understanding how biophysical cues change cell behavior provides groundwork to improve medical technologies such as tissue engineering, stem cell therapy, and mitigation of aberrant cell behavior. Microscopy is an indispensable tool that noninvasively explores the cell's nuclear state, providing valuable measurements on features including nuclear morphology, nuclear mechanical properties, protein localization, and genomic organization. In this review, we discuss notable imaging techniques, such as super-resolution microscopy, examples of how they have recently advanced the field, and how they can further our knowledge of the interplay between nuclear mechanoregulation and cell function.