Engineered regeneration最新文献

Conditioned medium (CM) derived from human umbilical cord-mesenchymal stem cells (hUC-MSCs) which contains numerous amounts of growth factors, has demonstrated potential in treatment of diabetic wounds. However, for practical application, a biodegradable supporting material is needed to hold the CM and fill in the injury site, where deep cavity wounds are often present in diabetic patients. Poly-l-lactic acid matrix coated with collagen (PLLA/CC) is a suitable carrier due to its biodegradability and biocompatibility. Thus, we present a method to immobilize the hUC-MSCs CM on PLLA/CC through freeze-drying process (PLLA/CC CM FD). When seeded on PLLA/CC CM FD, fibroblasts had an increased cellular function in producing collagen; although no enhancement in cell viability was observed. Moreover, implantation of PLLA/CC CM FD on the wound of diabetic rats showed improvement in wound closure and collagen deposition in the wound area. Altogether, this study exhibits the potential of PLLA/CC CM FD as a therapy for diabetic deep cavity wound.

Nucleus Pulposus (NP) Replacement is a developing surgical methodology for the treatment of pathology related to degeneration of intervertebral discs (IVDs). This article provides necessary context regarding the pathologies treated with this technology, the biomechanical structure and function of the IVD, and the procedures this technology aims to replace. Primarily, it provides an overview and discussion of commercial and experimental preformed and in situ curing prosthesis designs reported in the scientific literature and summarizes the results of biomechanical and clinical studies evaluating their efficacy. Contextual and updated information on the most recent research into NP replacement with novel hydrogel and tissue engineering (TE) strategies is described. Replacement of the NP allows for potential improvement in the treatment of degenerative spinal pathologies through minimally invasive surgical techniques.

Elevated levels of high mobility group protein B1 (HMGB1) play a significant role in the pathogenesis of many diseases, but is particularly important for the formation of malignant tumors. Nonetheless, the function of HMGB1 and the underlying mechanism of laryngeal squamous cell carcinoma (LSCC) remain incompletely understood, causing uncertainty. Here we found immunohistochemistry from 97 LSCC tissues showed HMGB1 was upregulated, which was associated with poor differentiation. HMGB1 knockdown could significantly inhibit wound closure and colony formation. The full-genome gene expression microarray was performed to investigate the mechanism. After knockdown of HMGB1 by siRNA, among the expressed differential genes, 10 genes were randomly selected for validation. Then, shRNA lentivirus targeting these genes were constructed to explore their role in LSCC by cell proliferation assay. LSM6 downregulation was dramatically promoted by HMGB1 knockdown, resulting in higher expression in LSCC tissues. Furthermore, downregulation of LSM6 could significantly suppress cell proliferation, migration and colony formation. This study indicated that HMGB1 promoted LSCC cell malignant phenotypes through regulation of LSM6. We anticipate that HMGB1-LSM6 could be a putative therapeutic target for LSCC.

The gut has been a focal point in the research of digestive system disorders. The internal microbiota generates metabolites that function as signaling molecules and substrates, interacting with the intestinal wall and influencing host physiology and pathology. Besides, the gut microbiota and metabolites owe highly diverse types and quantities, posing challenges for quantitative analysis, and monitoring frequent interactions between digestive tract metabolites and the intestinal wall remains a challenge. However, research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases. By modulating metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides, it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease. Currently, research on gut microbiota is advancing, and more work is required to explore the interactions between host, microbes and underlying mechanisms. In this review, we have revisited the generation of gut microbiota-related metabolites, their impact on diseases, and modes of interaction, emphasizing the significant role of metabolites in digestive system disorders. It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites, providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

Non-healing fractures, a global health concern arising from trauma, osteoporosis, and tumours, can lead to severe disabilities. Adenosine, integral to cellular energy metabolism, gains prominence in bone regeneration via adenosine A₂B receptor activation. This study introduces a controlled-release system for localized adenosine delivery, fostering human mesenchymal stromal cell (hMSC) differentiation into functional bone cells. The study investigates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media. Insights into adenosine-modulated signalling pathways during MSC differentiation, with osteogenic factors, provide a comprehensive understanding of the pathways involved. Analysing gene expression and metabolic profiles unravels adenosine's regulatory mechanisms in MSC differentiation. Sustained adenosine release from microparticles induces mineralization, synergizing with osteogenic media supplements, showcasing the potential of adenosine for treating critical bone defects and metabolic disorders. This study highlights the efficacy of a polymeric microparticle-based delivery system, offering novel strategies for bone repair. Unveiling adenosine's roles and associated signalling pathways advances our comprehension of molecular mechanisms steering bone regeneration, propelling innovative biomaterial, combined with metabolites, approaches for clinical use.

Following myocardial infarction (MI), cardiac tissue undergoes irreversible cellular alterations, with cardiomyocytes being replaced by fibrotic tissue. In order to improve tissue regeneration, a previously characterized chitosan-based cryogel, which was designed by our group, was used. The treatment regimen involved the sequential delivery of the cryogel loaded with specific cytokines and growth factors, followed by a separate injection of pre-differentiated cells. Initially, the cryogel loaded with interleukin-10 and transforming growth factor-β was injected into infarcted tissue immediately after MI induction, targeting the acute inflammatory response. On day four post-MI, a second injection was administered, this time utilizing cryogel loaded with vascular endothelial growth factor and fibroblast growth factor-2, aimed at promoting tissue regeneration and angiogenesis. Subsequently, on day six post-MI, the experimental group received cardiomyocyte-like cells, smooth muscle cells, and endothelial cells. The purpose of these cells, in synergy with cytokines and growth factors, was to repopulate the lost cellular populations, thereby enhancing myocardial repair. The treatment improved myocardial tissue regeneration, increased cardiac output, ejection fraction, and reduced fibrotic regions. Thus, the chitosan-based cryogel, enriched with anti-inflammatory and proangiogenic factors and supplemented with pre-differentiated cells, offers a promising platform for controlled release of therapeutics, promoting substantial tissue repair and regeneration following MI.

Persistent inflammatory responses often occur when bacteria and other microorganisms frequently invade and colonize open wounds and eventually result in the formation of chronic wounds. Therefore, achieving real-time detection of invasive bacteria accurately and promptly is essential for efficient wound management and accelerating the healing process. Recently, flexible wearable sensors have garnered significant attention, especially those designed for monitoring real-time biophysical or biochemical signals in wound sites in a minimally invasive manner. They provide more precise and continuous monitoring data, making them as emerging tools for clinical diagnostics. In this review, we first discuss the species and community distribution of different types of bacteria in chronic wounds. Next, we introduce currently developed techniques for detecting bacteria at wound sites. Following that, we discuss the recent progress and unresolved issues of various flexible wearable sensors in detecting bacteria at wound sites. We believe that this review can provide meaningful guidance for the development of flexible wearable sensors for bacteria detection.

Osteosarcoma (OS) is one of the most common malignant tumors in children and young adults. As chemotherapy and other therapies are limited by low therapeutic efficiency, severe side effects and single therapeutic function, it is of high value to develop innovative therapies for precise and efficient treatment of OS. Herein, natural photosynthetic microalgae (C. vulgaris, CV) were utilized as carriers for the chemotherapeutic agent doxorubicin (DOX) to create a multifunctional therapeutic platform (CV@DOX) for the photo-modulation of the tumor microenvironment (TME) and synergistic chemo-photodynamic therapy of osteosarcoma. CV@DOX exhibited rapid drug release behavior in the acidic TME, improving the efficiency of chemotherapy against tumors and reducing side effects on other normal tissues. Under 650 nm laser irradiation, CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species (ROS), thereby enhancing photodynamic therapy (PDT). CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis, inhibiting tumor proliferation and angiogenesis. Moreover, chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after administration. Finally, CV@DOX did not cause significant hematological and tissue toxicity, and prevented DOX-induced cardiotoxicity, showing good in vivo biocompatibility. Overall, this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosarcoma treatment.

Microfluidic is a technology that allows the precise control of fluid in a micro-channel. With its advantages of high throughput and low cost, microfluidic technology has achieved good performance in various fields in recent years. Arthritis is a general term for a variety of joint diseases, which can be clinically manifested as joint pain and swelling, seriously affecting people's physical and mental health. At present, the causes of arthritis disease are still unknown, and existing disease models and treatment methods are still limited, so more treatments need to be developed. Microfluidic organ chip is a cutting-edge technology to build a bionic human organ model, which can reflect the structure and function characteristics of human organs by simulating the physiological environment of tissues and cells in vitro. This paper reviews the application of microfluidic technology in the modeling and treatment of arthritis, hoping to open up a new vision for the study of arthritis.

Almost every life form, from the tiniest bacterium to humans, is mechanosensitive, implying it can use mechanical stresses to trigger certain physiological responses in the form of electric signals. Mechanotransduction largely relies on ion channels that respond to mechanical forces, such as the epithelial sodium channels/degenerins, transient receptor potential channel, and the two-pore domain potassium channel. Piezo1 and Piezo2 proteins were discovered to be the biggest non-selective mechanosensitive cation channels in the cell membrane. A substantial amount of research has previously been published on the Piezo channel's function in touch sensation, balance, and cardiovascular regression. However, the mechanistic perspective must be refined to fully understand the role of Piezo proteins in tissue engineering. This review centers on the latest insights into the structure of Piezo channels, activation mechanisms, and its interactions with cytoskeletal components, by emphasizing the physiological activities of Piezo channels in different tissues. The study also places focus on the possibilities of targeting this cation channel family as a tissue regeneration aid.