Engineered regeneration最新文献

The extrusion-based bioprinting (EBBP) applications in the medical field tremendously increase due to its versatility in fabricating intricate geometry components with reasonable accuracy and precision. The bioink and its properties for an EBBP process are crucial in manufacturing parts with significant biocompatibility and functionality. The EBBP demands optimized parameters for obtaining good printability and cell viability. A better understanding of the various process parameters is essential for the researcher to optimize the mechanical and biological properties of the printed constructs. The biological, mechanical, and rheological parameters all together need to be evaluated to enhance the printability of tissue. This article concisely delineates the effect of the rheological and physiochemical parameters on the biological and mechanical properties of the printed tissues. The printing parameters and nozzle geometry, which considerably influence the printability, and shape fidelity of the bioprinted scaffolds are exemplified in detail. Additionally, the challenges and future aspects of enhancing printability are discussed succinctly.

Micro-robots (MRs) are miniature machines with dimensions smaller than 1 mm and have semi- or fully-autonomous capabilities, including sensing, decision-making, and performing operations. These MRs have garnered significant attention in the precision medicine and personalized treatment field due to their ability to navigate narrow areas of the human body with non-desirable fluid flow. Specifically, MRs are actuated by a mechanism that generates propulsive force through the interaction between MRs' actuation modules and external energy sources in a specific direction. This driving mechanism enables the precise execution of medical treatment such as targeted drug delivery and minimally invasive surgeries. Nonetheless, MRs currently encounter certain challenges in clinical practice, including reliance on external energy sources, short lifespan, and difficulties in degradation or recovery within the human body. This article aims to review the common components and characteristics of driving mechanism for MRs' actuation modules, propose possible solutions to address current clinical challenges, and ultimately, explore the desirable structural and functional composition for the future development of MRs. Through these efforts, this review hopes to provide guidance for the future development of MRs in the field of precision medicine.

Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.

Exosomes are nanoscale membrane-enclosed extracellular vesicles secreted by various cells, which have enormous potential as disease biomarkers for clinical application. However, the isolation and detection of exosomes remain enormous challenges, which limits their further application. Herein, inspired by immunomagnetic beads, a magnetic nanoparticle conjugated aptamer was repurposed for the effective capture and detection of exosomes. The magnetic nanoparticles, composed of Fe₃O₄ synthesized by the hydrothermal method as the core and coupled with gold nanoparticles (Fe₃O₄@Au), provide a large specific surface area, making the resulting composite material an effective platform for exosome capture. Furthermore, the elution of captured exosomes with 1.0 M NaCl made downstream analysis of exosomes possible. The preliminary clinical application value of the composite in exosome analyses of serum from healthy individuals and patients with Alzheimer's disease (AD) has also been verified, which could provide a promising platform for biomedical and clinical diagnosis.

Extracellular vesicles (EVs) are nanoscale substances produced by most cells, which were not fully understood in the early years. However, with the development of advanced techniques, researchers have discovered that EVs play an essential role in information exchange and signal transduction between cells. Nowadays, EVs are being used, modified, and developed as a natural drug carrier in various medical fields because of their high biocompatibility and natural affinity with the source body. Many studies have shown that multiple sources of EVs have been modified and utilized in cancer therapy to improve patients' treatment windows and effectively prolong patient survival. In this paper, we review the advances in the treatment of cancer based on EVs. We summarize the types of EVs loading therapy, the modes of drug loading and the latest therapeutic applications of multiple modes combined with EVs in cancer treatment. We conclude with a discussion of the current status, challenges, and prospects of EVs as a tool for tumor therapy.

Inflammatory bowel disease (IBD) is a systemic disorder affecting intestinal tract and other organs outside the gut, known as extraintestinal manifestations (EIMs). These EIMs are complex and diverse, and early treatment may reduce teratogenic rates and improve quality of life. However, our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight. Fortunately, advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs. The gut microbiota can drive aberrant immune activation and intestinal inflammation. Intriguingly, chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis. Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function. Furthermore, gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites, leading to systemic inflammatory responses. The microbiome is showing its potential in treating IBD and EIMs, and microbial engineering approaches, such as probiotic engineering and engineered fecal microbiota transplantation, are exhibiting great promise for IBD therapeutics.

The skin is an important organ of the human body that resists external threats but lacks sufficient self-regeneration ability when severe damage occurs. However, most of the available skin substitutes cannot achieve ideal restoration of complex structures and multiple functions of native skin tissues. Fortunately, the advent of decellularized extracellular matrix (dECM) offers a promising approach to overcome these obstacles. The dECM, derived from the natural extracellular matrix (ECM), possesses a similar structure and composition, which constructs an environment favorable for cell performance in regeneration. Moreover, dECM retains good bioactivity, low immunogenicity, and high availability, making it a suitable biomaterial for skin repair and regeneration. In this review, various decellularization methods and subsequent evaluations of dECM are introduced first, and the main sources of dECM are then presented. Furthermore, the recent progress of dECM-based biomaterials applied in skin regeneration and future perspectives are summarized.

Cells, wrapped among their neighbors and surrounding extracellular matrix (ECM), form cell-cell adhesions and cell-ECM adhesions. Extracellular biophysical cues exert a far-reaching influence on a sweeping of cell behaviors, including signal transduction, gene expression, and fate determination. Cell-cell adhesions mediated by intercellular adhesion molecules bridge the membranes of adjacent cells through either heterophilic or homophilic adhesive interactions, playing a critical part in multicellular structural maintenance and, therefore, a foundation for multicellular organisms. Cell-ECM adhesions are derived from the interaction between cell adhesion receptors and multi-adhesive matrix proteins to ensure cell and tissue cohesion. Whereas cells not only unilaterally respond to certain cues from extracellular environment but can also alter the physicochemical profiles of the externalities and hence hold important implications for clinical applications. The essential function of cell adhesions has created tremendous interests in developing methods for measuring and studying cell adhesion properties, namely, cellular force. Here, we describe the collection of cell adhesive inputs on cellular signaling cascades and the “crosstalk” between cell-cell adhesions and cell-ECM adhesions. Furthermore, we provide the summary of the current methods to measure such cell adhesive forces.

Sensory hair cells are responsible for detecting and transmitting sound in the inner ear, and damage to HCs leads to hearing loss. HCs do not regenerate spontaneously in adult mammals, which makes the hearing loss permanent. However, hair cells and supporting cells have the same precursors in the inner ear, and in newborn mice, the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells. Here, we demonstrate the role of the Ras association domain family member 2 (Rassf2) in supporting cell to hair cell trans-differentiation in the inner ear. Using the AAV vector (AAV-ie) to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids. Also, AAV-Rassf2 enhanced the regenerative ability of Lgr5⁺ SCs in the postnatal cochlea without impairing hearing, and this might due to the modulation of the Wnt, Hedgehog and Notch signaling pathways. Furthermore, AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model. In summary, our results suggest that Rassf2 is a key component in HC regenerative repair, and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.