Clinical-pathological features and muscle imaging findings in 36 Chinese patients with rimmed vacuolar myopathies: case series study and review of literature.

Introduction: Rimmed vacuolar myopathies (RVMs) are a group of genetically heterogeneous diseases that share histopathological characteristics on muscle biopsy, including the aberrant accumulation of autophagic vacuoles. However, the presence of non-coding sequences and structural mutations, some of which remain undetectable, confound the identification of pathogenic mutations responsible for RVMs. Therefore, we assessed the clinical profiles and muscle magnetic resonance imaging (MRI) changes in 36 Chinese patients with RVMs, emphasizing the role of muscle MRI in disease identification and differential diagnosis to propose a comprehensive literature-based imaging pattern to facilitate improved diagnostic workup. Methods: All patients presented with rimmed vacuoles with varying degrees of muscular dystrophic changes and underwent a comprehensive evaluation using clinical, morphological, muscle MRI and molecular genetic analysis. We assessed muscle changes in the Chinese RVMs and provided an overview of the RVMs, focusing on the patterns of muscle involvement on MRI. Results: A total of 36 patients, including 24 with confirmed distal myopathy and 12 with limb-girdle phenotype, had autophagic vacuoles with RVMs. Hierarchical clustering of patients according to the predominant effect of the distal or proximal lower limbs revealed that most patients with RVMs could be distinguished. GNE myopathy was the most prevalent form of RVMs observed in this study. Moreover, MRI helped identify the causative genes in some diseases (e.g., desminopathy and hereditary myopathy with early respiratory failure) and confirmed the pathogenicity of a novel mutation (e.g., adult-onset proximal rimmed vacuolar titinopathy) detected using next-generation sequencing. Discussion: Collectively, our findings expand our knowledge of the genetic spectrum of RVMs in China and suggest that muscle imaging should be an integral part of assisting genetic testing and avoiding misdiagnosis in the diagnostic workup of RVM.

Tissue-mimetic hybrid bioadhesives for intervertebral disc repair.

Intervertebral disc (IVD) degeneration and herniation often necessitate surgical interventions including a discectomy with or without a nucleotomy, which results in a loss of the normal nucleus pulposus (NP) and a defect in the annulus fibrosus (AF). Due to the limited regenerative capacity of the IVD tissue, the annular tear may remain a persistent defect and result in recurrent herniation post-surgery. Bioadhesives are promising alternatives but show limited adhesion performance, low regenerative capacity, and inability to prevent re-herniation. Here, we report hybrid bioadhesives that combine an injectable glue and a tough sealant to simultaneously repair and regenerate IVD post-nucleotomy. The glue fills the NP cavity while the sealant seals the AF defect. Strong adhesion occurs with the IVD tissues and survives extreme disc loading. Furthermore, the glue can match native NP mechanically, and support the viability and matrix deposition of encapsulated cells, serving as a suitable cell delivery vehicle to promote NP regeneration. Besides, biomechanical tests with bovine IVD motion segments demonstrate the capacity of the hybrid bioadhesives to restore the biomechanics of bovine discs under cyclic loading and to prevent permanent herniation under extreme loading. This work highlights the synergy of bioadhesive and tissue-engineering approaches. Future works are expected to further improve the tissue specificity of bioadhesives and prove their efficacy for tissue repair and regeneration.

Multifaceted Design and Emerging Applications of Tissue Adhesives.

Tissue adhesives can form appreciable adhesion with tissues and have found clinical use in a variety of medical settings such as wound closure, surgical sealants, regenerative medicine, and device attachment. The advantages of tissue adhesives include ease of implementation, rapid application, mitigation of tissue damage, and compatibility with minimally invasive procedures. The field of tissue adhesives is rapidly evolving, leading to tissue adhesives with superior mechanical properties and advanced functionality. Such adhesives enable new applications ranging from mobile health to cancer treatment. To provide guidelines for the rational design of tissue adhesives, here, existing strategies for tissue adhesives are synthesized into a multifaceted design, which comprises three design elements: the tissue, the adhesive surface, and the adhesive matrix. The mechanical, chemical, and biological considerations associated with each design element are reviewed. Throughout the report, the limitations of existing tissue adhesives and immediate opportunities for improvement are discussed. The recent progress of tissue adhesives in topical and implantable applications is highlighted, and then future directions toward next-generation tissue adhesives are outlined. The development of tissue adhesives will fuse disciplines and make broad impacts in engineering and medicine.

Triggered micropore-forming bioprinting of porous viscoelastic hydrogels.

Cell-laden scaffolds of architecture and mechanics that mimic those of the host tissues are important for a wide range of biomedical applications but remain challenging to bioprint. To address these challenges, we report a new method called triggered micropore-forming bioprinting. The approach can yield cell-laden scaffolds of defined architecture and interconnected pores over a range of sizes, encompassing that of many cell types. The viscoelasticity of the bioprinted scaffold can match that of biological tissues and be tuned independently of porosity and stiffness. The bioprinted scaffold also exhibits superior mechanical robustness despite high porosity. The bioprinting method and the resulting scaffolds support cell spreading, migration, and proliferation. The potential of the 3D bioprinting system is demonstrated for vocal fold tissue engineering and as an in vitro cancer model. Other possible applications are foreseen for tissue repair, regenerative medicine, organ-on-chip, drug screening, organ transplantation, and disease modeling.

Magnetic microboats for floating, stiffness tunable, air-liquid interface epithelial cultures.

To study respiratory diseases, in vitro airway epithelial models are commonly implemented by culturing airway cells on a porous surface at an air-liquid interface (ALI). However, these surfaces are often supraphysiologically stiff, which is known to affect the organization, maturation, and responses of cells to potential therapies in other biological culture models. While it is possible to culture cells on soft hydrogel substrates at an air-liquid interface, these techniques are challenging to implement particularly in high-throughput applications which require robust and repetitive material handling procedures. To address these two limitations and characterize epithelial cultures on substrates of varying stiffness at the ALI, we developed a novel "lung-on-a-boat", in which stiffness-tuneable hydrogels are integrated into the bottoms of polymeric microstructures, which normally float at the air-liquid interface. An embedded magnetic material can be used to sink the boat on demand when a magnetic field is applied, enabling reliable transition between submerged and ALI culture. In this work, we prototype a functional ALI microboat platform, with integrated stiffness-tunable polyacrylamide hydrogel surfaces, and validate the use of this technology with a model epithelial cell line. We verify sufficient transport through the hydrogel base to maintain cell viability and stimulate cultures, using a model nanoparticle with known toxicity. We then demonstrate significant morphological and functional effects on epithelial barrier formation, suggesting that substrate stiffness is an important parameter to consider in the design of in vitro epithelial ALI models for drug discovery and fundamental research.

Gotta catch 'em all: the microscale quest to understand cancer biology.

Developing an improved understanding of the processes that drive cancer initiation and progression has been the focus of intense research in recent years. Here, we highlight recent advances in the innovative use of microscale engineered technologies to gain new insight into the integrative biophysical mechanisms that drive these processes.