Current Opinion in Biomedical Engineering最新文献

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.

3D bioprinting has recently emerged as a successful biofabrication strategy for replicating the complex in vivo hepatic milieu. Significant research advances in this field have allowed for the fabrication of biomimetic hepatic tissues with potential applications in the healthcare (regeneration, transplantation, drug discovery) and diagnostic sectors (in vitro disease models). This article initially delves into describing the hepatic tissue architecture and function, followed by a rational exposition of how 3D bioprinting potentiates the better development of functional liver tissue compared to traditional tissue engineering approaches and 3D cell culture platforms. This review then highlights the recent breakthroughs and reliable strategies for replicating liver structure and function through bioprinting approaches. In this context, we have systematically described the current landscape of hepatic bioprinting, initially focusing on the cell sources used, followed by the biomaterials and strategies implemented to prolong their in vitro viability. Proceeding forward, we have critically highlighted essential aspects of hepatic bioprinting, such as developing tissue-specific bioinks, strategies to induce vascularization within bioprinted liver constructs, and replication of native liver tissue heterogeneity through spatial distribution of multiple cell types in predetermined patterns. In our concluding remarks, we discuss the existing bottlenecks that prevail in this field and provide our viewpoint regarding possible future directions to overcome them.

Duchenne muscular dystrophy (DMD) is a hereditary disease characterized by severe muscle weakness resulting from DYSTROPHIN deficiency-associated damage. Muscle regeneration therapy using skeletal muscle stem cell (MuSC) transplantation has demonstrated great promise. Optimized differentiation methods yield efficient induced pluripotent stem cell-derived MuSCs (iMuSCs); transplanted iMuSCs have high regenerative potential in DMD mouse models. However, achieving complete pathophysiological recovery of DMD motor function through cell therapy alone is challenging. According to recent studies, exercise can significantly improve DMD pathophysiology. Current research aims to enhance therapeutic efficacy by combining cell transplantation with exercise interventions, addressing the limitations of cell-transplantation therapy for DMD.

The nuclear envelope (NE) has a dual role of serving as a protective shell for the genome and a critical communication interface that compartmentalizes cells into cytoplasmic and nuclear domains. The NE is reinforced by the integrated scaffold of nuclear lamins, heterochromatin, nuclear pores, and other NE proteins with critical roles in regulating the three-dimensional architecture of the genome. Importantly, this interface is in the direct path of force transduction, emanating from the cell-extrinsic environment and generated by the cells themselves, leading to deformation of the nucleus. Alterations in the mechanical properties of NE components have profound implications for cellular dysfunction, aging, and disease. Here we discuss some of the recent findings on the biophysical properties of the nuclear periphery and how NE-derived signaling and nuclear remodeling serve as gatekeepers of genome integrity, normal ploidy, and cellular function.

Recent innovations in the field of gene therapy have paved the way for advances towards developing genome editing medicines. Despite these steps forward, challenges with viral delivery of genome editing tools persist. Efforts currently underway include developing next-generation genome editors, overcoming adeno-associated virus (AAV) packaging restrictions, improving AAV genome integrity, engineering novel AAV capsids, and minimizing the immune response. This review discusses current challenges in delivering CRISPR-Cas nuclease-based genome editing therapies using AAV and highlights emerging methods to overcome these obstacles. This includes developing smaller payloads and regulatory elements, advancing novel sequencing methods for vector characterization, engineering capsids with enhanced potency, tissue-selectivity, and ability to evade pre-existing antibodies, controlling transgene expression, and minimizing the immune response to Cas proteins.

Peripheral nerve injury (PNI) causes long-term dysfunction and significantly affect patients' quality of life. However, regenerative rehabilitation, which combines rehabilitation and regenerative medicine approaches, has shown promising progress in promoting nerve regeneration after PNI. This article reviews rehabilitation methods and therapeutic electrophysical agents (EPAs) for promoting nerve regeneration, their possible mechanisms, and the progress achieved to date in the treatment of PNI using regenerative rehabilitation with EPAs. We also discuss several factors that have the potential to optimize treatment outcomes, including the intervention target, timing, and duration. This review provides a comprehensive overview of advancements in the treatment of PNI, possible strategies to maximize treatment efficacy, and the challenges that need to be addressed.