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Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.

Summary: Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

Background: Hyperuricemia elevates gut permeability; however, the risk of its influence on the compromised intestinal barrier is poorly understood. Aims: This study was carried out, aiming to elucidate the orchestrators and disruptors of intestinal barrier in hyperuricemia. Methods: A mouse model of hyperuricemia was induced by administering adenine and oteracil potassium to mice. Allopurinol was used to decrease uric acid level, and antibiotics were administered to mice to deplete gut microbiota. Intestinal permeability was assessed using FITC-labeled dextran. Changes in gut microbial community were analyzed through 16S rRNA sequencing. IL-1β and TNF-α levels were quantified using ELISA. The expression of tight junction protein genes, TLR4, p65 and IL-1β, was determined with Q-PCR and Western blotting. Results: Allopurinol treatment effectively reduced intestinal permeability and serum TNF-α levels. Antibiotic treatment alleviated but not abolished intestinal permeability. Uric acid alone was insufficient to increase Coca2 monolayer permeability. Allopurinol treatment altered microbial composition and suppressed opportunistic infections. Re-establishing hyperuricemia in a germfree mouse model protected mice from intestinal injury. Allopurinol and antibiotic treatments reduced TLR4 and IL-1β expressions, increased occludin and claudin-1 expressions but suppressed NF-ĸB p65 signaling. However, removing gut microbiota aggravated lipid metabolic dysfunction. Conclusion: Gut microbiota is a direct and specific cause for intestinal barrier dysfunction.

In this study, the properties of controlled low strength material (CLSM) made from waste soil were examined, utilizing 53 different mix proportions, and a dataset was subsequently constructed. Models, such as particle swarm optimization (PSO)-support vector regression (SVR), genetic algorithm (GA)-SVR, and grid search (GS)-SVR, were developed to predict both flowability and unconfined compressive strength (UCS). To assess the models’ performance, comparisons between experimental and predicted values, residual distribution histograms, and evaluation criteria were conducted. Results revealed that all three models effectively predicted the flowability and UCS of CLSM made from waste soil. Predicted values closely aligned with experimental values in both training and testing sets. Notably, GA-SVR exhibited greater accuracy when compared to PSO-SVR and GS-SVR. Evaluation criteria, including correlation coefficient (R2), mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) for GA-SVR in assessing flowability were 0.948, 77.899, 8.826, 7.608, and 3.061 %, respectively. Correspondingly, for UCS, the values were 0.934, 0.032, 0.178, 0.115, and 8.956 %, respectively. Furthermore, the histogram depicting the residual distribution of the GA-SVR model closely resembled a normal distribution, characterized by a small mean and standard deviation. Extending the analysis to 45 compression strength data points obtained from public literature, the three models continued to demonstrate effective predictive capabilities, with the GA-SVR model outperforming the others. The evaluation criteria, including R2, MSE, RMSE, MAE, and MAPE in this context were 0.909, 0.011, 0.105, 0.085, and 15.502 %, respectively. Shapley additive explanation (SHAP) values highlighted water as the most crucial input variable in the flowability model. Additionally, water, superplasticizer (SP), and sand positively impacted flowability, whereas soil, fly ash (FA), and cement exerted negative effects. In the UCS model, curing age (CA) emerged as the most important input variable. CA, cement, FA, sand, and soil positively influenced UCS, while water and SP had negative effects. This study is of considerable importance in the accurate prediction and evaluation of CLSM engineering properties, as well as in optimizing mix proportions.

Traditional hydrogel design and optimization methods usually rely on repeated experiments, which is time-consuming and expensive, resulting in a slow-moving of advanced hydrogel development. With the rapid development of artificial intelligence (AI) technology and increasing material data, AI-energized design and optimization of hydrogels for biomedical applications has emerged as a revolutionary breakthrough in materials science. This review begins by outlining the history of AI and the potential advantages of using AI in the design and optimization of hydrogels, such as prediction and optimization of properties, multi-attribute optimization, high-throughput screening, automated material discovery, optimizing experimental design, and etc. Then, we focus on the various applications of hydrogels supported by AI technology in biomedicine, including drug delivery, bio-inks for advanced manufacturing, tissue repair, and biosensors, so as to provide a clear and comprehensive understanding of researchers in this field. Finally, we discuss the future directions and prospects, and provide a new perspective for the research and development of novel hydrogel materials for biomedical applications.

Introduction: The intricate interplay between gut microbiota and hyperuricemia remains a subject of growing interest. However, existing studies only provided snapshots of the gut microbiome at single time points, the temporal dynamics of gut microbiota alterations during hyperuricemia progression and the intricate interplay between the gut barrier and microbiota remain underexplored. Our investigation revealed compelling insights into the dynamic changes in both gut microbiota and intestinal barrier function throughout the course of hyperuricemia. Methods: The hyperuricemia mice (HY) were given intragastric administration of adenine and potassium oxalate. Gut microbiota was analyzed by 16S rRNA sequencing at 3, 7, 14, and 21 days after the start of the modeling process. Intestinal permeability as well as LPS, TNF-a, and IL-1ß levels were measured at 3, 7, 14, and 21 days. Results: We discovered that shifts in microbial community composition occur prior to the onset of hyperuricemia, key bacterial Bacteroidaceae, Bacteroides, and Blautia exhibited reduced levels, potentially fueling microbial dysbiosis as the disease progresses. During the course of hyperuricemia, the dynamic fluctuations in both uric acid levels and intestinal barrier function was accompanied with the depletion of key beneficial bacteria, including Prevotellaceae, Muribaculum, Parabacteroides, Akkermansia, and Bacteroides, and coincided with an increase in pathogenic bacteria such as Oscillibacter and Ruminiclostridium. This microbial community shift likely contributed to elevated lipopolysaccharide (LPS) and proinflammatory cytokine levels, ultimately promoting metabolic inflammation. The decline of Burkholderiaceae and Parasutterella was inversely related to uric acid levels, Conversely, key families Ruminococcaceae, Family_XIII, genera Anaeroplasma exhibited positive correlations with uric acid levels. Akkermansiaceae and Bacteroidaceae demonstrating negative correlations, while LPS-containing microbiota such as Desulfovibrio and Enterorhabdus exhibited positive correlations with intestinal permeability. Conclusion: In summary, this study offers a dynamic perspective on the complex interplay between gut microbiota, uric acid levels, and intestinal barrier function during hyperuricemia progression. Our study suggested that Ruminiclostridium, Bacteroides, Akkermansiaceae, Bilophila, Burkholderiaceae and Parasutterella were the key bacteria that play vital rols in the progress of hyperuricemia and compromised intestinal barrier, which provide a potential avenue for therapeutic interventions in hyperuricemia. [ABSTRACT FROM AUTHOR]