3D cryo-printed hierarchical porous scaffolds provide immobilization of surface-functionalized sleep-inspired small extracellular vesicles: synergistic therapeutic strategies for vascularized bone regeneration based on macrophage phenotype modulation and angiogenesis-osteogenesis coupling.

Bone defect healing is a multi-factorial process involving the inflammatory microenvironment, bone regeneration and the formation of blood vessels, and remains a great challenge in clinical practice. Combined use of three-dimensional (3D)-printed scaffolds and bioactive factors is an emerging strategy for the treatment of bone defects. Scaffolds can be printed using 3D cryogenic printing technology to create a microarchitecture similar to trabecular bone.

Bilayer Scaffolds Synergize Immunomodulation and Rejuvenation via Layer-Specific Release of CK2.1 and the "Exercise Hormone" Lac-Phe for Enhanced Osteochondral Regeneration.

Repairing osteochondral defects necessitates the intricate reestablishment of the microenvironment. The cartilage layer consists of a porous gelatin methacryloyl hydrogel (PGelMA) covalently crosslinked with the chondroinductive peptide CK2.1 via a "linker" acrylate-PEG-N-hydroxysuccinimide (AC-PEG-NHS).

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs).

Polymeric coating on β-TCP scaffolds provides immobilization of small extracellular vesicles with surface-functionalization and ZEB1-Loading for bone defect repair in diabetes mellitus.

Repair of critical-size bone defects in patients with diabetes mellitus (DM) has always been a challenge in clinical treatment. The process of bone defect regeneration can be impaired by underlying diseases including DM, but the mechanism remains unclear. In bone tissue engineering, the integration of bionic coatings and bioactive components into basic scaffolds are common function-enhancing strategies.

Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis.

Osteoarthritis (OA), characterized by chondrocyte apoptosis and disturbance of the balance between catabolism and anabolism of the extracellular matrix (ECM), is the most common age-related degenerative joint disease worldwide. As sleep has been found to be beneficial for cartilage repair, and circular RNAs (circRNAs) have been demonstrated to be involved in the pathogenesis of OA, we performed RNA sequencing (RNA-seq), and found circRNA3503 was significantly increased after melatonin (MT)-induced cell sleep. Upregulation of circRNA3503 expression completely rescued the effects of interleukin-1β (IL-1β), which was used to simulate OA, on apoptosis, ECM degradation- and synthesis-related genes.

Small extracellular vesicles with LncRNA H19 "overload": YAP Regulation as a Tendon Repair Therapeutic Tactic.

Functional healing of tendon injuries remains a great challenge. Small extracellular vesicles (sEVs) have received attention as pro-regenerative agents. H19 overexpression could bring tendon regenerative ability, but the mechanism is still not fully elucidated, and reliable method for delivery of long non-coding RNAs (LncRNAs) was demanded.

Role of extracellular vesicles in tumour microenvironment.

In recent years, it has been demonstrated that extracellular vesicles (EVs) can be released by almost all cell types, and detected in most body fluids. In the tumour microenvironment (TME), EVs serve as a transport medium for lipids, proteins, and nucleic acids. EVs participate in various steps involved in the development and progression of malignant tumours by initiating or suppressing various signalling pathways in recipient cells.

EWSAT1 Acts in Concert with Exosomes in Osteosarcoma Progression and Tumor-Induced Angiogenesis: The "Double Stacking Effect".

The prognosis for osteosarcoma (OS) continues to be unsatisfactory due to tumor recurrence as a result of metastasis and drug resistance. Several studies have shown that Ewing sarcoma associated transcript 1 (EWSAT1) plays an important role in the progression of OS. Exosomes (Exos) act as important carriers in intercellular communication and play an important role in the tumor microenvironment, especially in tumor-induced angiogenesis.

A 3D-printed, personalized, biomechanics-specific beta-tricalcium phosphate bioceramic rod system: personalized treatment strategy for patients with femoral shaft non-union based on finite element analysis.

Background: Although double-plate fixation (DP), i.e., fixation with a combination of a main lateral plate (LP) and a support medial plate (MP), is a relatively mature method for treating femoral shaft non-union with bone defect causes complications.

J-bone graft with double locking plate: a symphony of mechanics and biology for atrophic distal femoral non-union with bone defect.

Objective: Atrophic distal femur non-union with bone defect (ADFNBD) has been a worldwide challenge to treat due to the associated biological and mechanical problems. The purpose of this study was to introduce a new solution involving the use of a J-shaped iliac crest bone graft (J-bone) combined with double-plate (DP) in the treatment of femoral non-union.

Methods: Clinically, 18 patients with ADFNBD were included in this retrospective study and were treated with a combination of J-bone graft and DP.

Extracellular vesicles in bone: "dogrobbers" in the "eternal battle field".

Throughout human life, bone is constantly in a delicate dynamic equilibrium of synthesis and resorption, hosting finely-tuned bone mineral metabolic processes for bone homeostasis by collaboration or symphony among several cell types including osteoclasts (OCs), osteoblasts (OBs), osteocytes (OYs), vascular endothelial cells (ECs) and their precursors. Beyond these connections, a substantial level of communication seems to occur between bone and other tissues, and together, they form an organic unit linked to human health and disease. However, the current hypothesis, which includes growth factors, hormones and specific protein secretion, incompletely explains the close connections among bone cells or between bone and other tissues.

[Research progress on the role of extracellular vesicles in bacterial pathogenesis].

Objective: To summarize the bioactive substances contained in bacterial extracellular vesicles (EVs) and their mechanisms in mediating bacterial-bacterial and bacterial-host interactions, as well as their mechanisms for use in implant infection-associated clinical guidance.

Methods: A wide range of publications on bacterial-derived EVs were extensively reviewed, analyzed, and summarized.

Results: Both gram-negative bacteria (G bacteria) and gram-positive bacteria (G bacteria) can secrete EVs which contain a variety of bioactive substances, including proteins, lipids, nucleic acids, and virulence factors, and mediate bacterial-bacterial and bacterial-host interactions.

Extracellular Vesicles: Potential Participants in Circadian Rhythm Synchronization.

The circadian rhythm (CR) is a set of autonomous endogenous oscillators. Exposure to the 24-hour day-night cycle synchronizes our CR system, maintaining homeostasis and human health. Several mechanisms for the CR system have been proposed, including those underlying the function (transcriptional-translational negative-feedback loops, or TTFLs), mechanisms regulating the TTFLs, and the mechanism by which the "server clock" is synchronized to environmental time.

Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles.

Extracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years.

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine.

Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation.

Valproic acid prevents glucocorticoid‑induced osteonecrosis of the femoral head of rats.

Glucocorticoids (GCs) are the most common cause of atraumatic osteonecrosis of the femoral head (ONFH) because their effect compromises the osteogenic capability of bone marrow‑derived mesenchymal stem cells (BMSCs). Valproic acid (VPA) is a widely used anti‑epileptic and anti‑convulsant drug. Previous studies have reported that VPA promotes osteogenic differentiation of MSCs in vitro and osteogenesis in vivo as a histone deacetylase (HDAC) inhibitor.

Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds.

Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest.

Human urine-derived stem cells contribute to the repair of ischemic acute kidney injury in rats.

Acute kidney injury (AKI) is a clinical syndrome associated with high rates of morbidity and mortality. It has previously been reported that stem cells may be considered a potential therapeutic strategy for the treatment of AKI. The present study aimed to determine whether administration of urine‑derived stem cells (USCs) to rats with ischemia/reperfusion (I/R)‑induced AKI could improve renal function.

Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach.

Extracellular vesicles (EVs) are a newly-discovered way by which cells communicate with their neighbors, as well as transporting cargos which once were considered to be limited by membrane barriers, including membrane proteins, cytosolic proteins and RNA. The discovery of platelet-derived EVs (P-EVs), the most abundant EVs in human blood, has been a very tortuous process. At first, P-EVs were identified as nothing but 'platelet dust', and subsequent research did not progress smoothly because of the limited research techniques to study EVs.

Chitosan Wound Dressings Incorporating Exosomes Derived from MicroRNA-126-Overexpressing Synovium Mesenchymal Stem Cells Provide Sustained Release of Exosomes and Heal Full-Thickness Skin Defects in a Diabetic Rat Model.

There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA-126-3p (miR-126-3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis.

Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway.

An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis.

Role of Phosphorylated HDAC4 in Stroke-Induced Angiogenesis.

Acetylation or deacetylation of chromatin proteins and transcription factors is part of a complex signaling system that is involved in the control of neurological disorders. Recent studies have demonstrated that histone deacetylases (HDACs) exert protective effects in attenuating neuronal injury after ischemic insults. Class IIa HDAC4 is highly expressed in the brain, and neuronal activity depends on the nucleocytoplasmic shuttling of HDAC4.

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model.

Objectives: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion.

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model.

Chronic wounds have become an economic, social, and public health burden and need advanced treatment. Platelet-rich plasma (PRP) has been used extensively in treatment of chronic wounds because it contains an abundance of growth factors secreted by platelets. The exosomes derived from PRP (PRP-Exos) have been proven to encapsulate principal growth factors from platelets.