Pluronic F127 hydrogel-loaded extracellular vesicles from adipose-derived mesenchymal stem cells promote tracheal cartilage regeneration via SCNN1B delivery.

Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (AMSC-EVs) have been highlighted as a cell-free therapy due to their regenerative capability to enhance tissue and organ regeneration. Herein, we aimed to examine the mechanism of PF127-hydrogel@AMSC-EVs in promoting tracheal cartilage defect repair. Based on bioinformatics methods, SCNN1B was identified as a key gene for the osteogenic differentiation of AMSCs induced by AMSC-EVs. EVs were isolated from rat AMSCs and then loaded onto thermo-sensitive PF-127 hydrogel to develop PF127-hydrogel@AMSC-EVs. It was established that PF127-hydrogel@AMSC-EVs could effectively deliver SCNN1B into AMSCs, where SCNN1B promoted AMSC osteogenic differentiation. The promotive effect was evidenced by enhanced ALP activity, extracellular matrix mineralization, and expression of s-glycosaminoglycan, RUNX2, OCN, collagen II, PERK, and ATF4. Furthermore, the in vivo experiments revealed that PF127-hydrogel@AMSC-SCNN1B-EVs stimulated tracheal cartilage regeneration in rats through PERK/ATF4 signaling axis activation. Therefore, PF127-hydrogel@AMSC-SCNN1B-EVs may be a novel cell-free biomaterial to facilitate tracheal cartilage regeneration and cartilage injury repair.

Application of smart hydrogel materials in cartilage injury repair: A systematic review and meta-analysis.

OBJECTIVE: Cartilage injury is a common clinical condition, and treatment approaches have evolved over time from traditional conservative and surgical methods to regenerative repair. In this context, hydrogels, as widely used biomaterials in the field of cartilage repair, have garnered significant attention. Particularly, responsive hydrogels (also known as "smart hydrogels") have shown immense potential due to their ability to respond to various physicochemical properties and environmental changes. This paper aims to review the latest research developments of hydrogels in cartilage repair, utilizing a more systematic and comprehensive meta-analysis approach to evaluate the research status and application value of responsive hydrogels. The goal is to determine whether these materials demonstrate favorable therapeutic effects for subsequent clinical applications, thereby offering improved treatment methods for patients with cartilage injuries. METHOD: This study employed a systematic literature search method to summarize the research progress of responsive hydrogels by retrieving literature on the subject and review studies. The search terms included "hydrogel" and "cartilage," covering data from database inception up to October 2023. The quality of the literature was independently evaluated using Review Manager v5.4 software. Quantifiable data was statistically analyzed using the R language. RESULTS: A total of 7 articles were retrieved for further meta-analysis. In the quality assessment, the studies demonstrated reliability and accuracy. The results of the meta-analysis indicated that responsive hydrogels exhibit unique advantages and effective therapeutic outcomes in the field of cartilage repair. Subgroup analysis revealed potential influences of factors such as different types of hydrogels and animal models on treatment effects. CONCLUSION: Responsive hydrogels show significant therapeutic effects and substantial application potential in the field of cartilage repair. This study provides strong scientific evidence for their further clinical applications and research, with the hope of promoting advancements in the treatment of cartilage injuries.

Nanoplastic pollution changes the intestinal microbiome but not the morphology or behavior of a freshwater turtle.

Humans produce 350 million metric tons of plastic waste per year, leading to microplastic pollution and widespread environmental contamination, particularly in aquatic environments. This subsequently impacts aquatic organisms in myriad ways, yet the vast majority of research is conducted in marine, rather than freshwater systems. In this study, we exposed eggs and hatchlings of the Chinese soft-shelled turtle (Pelodiscus sinensis) to 80-nm polystyrene nanoplastics (PS-NPs) and monitored the impacts on development, behavior and the gut microbiome. We demonstrate that 80-nm PS-NPs can penetrate the eggshell and move into developing embryos. This led to metabolic impairments, as evidenced by bradycardia (a decreased heart rate), which persisted until hatching. We found no evidence that nanoplastic exposure affected hatchling morphology, growth rates, or levels of boldness and exploration, yet we discuss some potential caveats here. Exposure to nanoplastics reduced the diversity and homogeneity of gut microbiota in P. sinensis, with the level of disruption correlating to the length of environmental exposure (during incubation only or post-hatching also). Thirteen core genera (with an initial abundance >1 %) shifted after nanoplastic treatment: pathogenic bacteria increased, beneficial probiotic bacteria decreased, and there was an increase in the proportion of negative correlations between bacterial genera. These changes could have profound impacts on the viability of turtles throughout their lives. Our study highlights the toxicity of environmental NPs to the embryonic development and survival of freshwater turtles. We provide insights about population trends of P. sinensis in the wild, and future directions for research.

Health status of children's first permanent molars in Henan province from 2015 to 2020.

OBJECTIVES: To investigate the eruption, caries, and pit and fissure sealing of the first permanent molars in children aged 6-9 years in Henan province. METHODS: The data of oral health examination in Henan province from 2015 to 2020 were analyzed in the information management system of China Children Oral Disease Comprehensive Intervention Project. RESULTS: Among 486 865 children in Henan province, the total eruption rate of the four first permanent molars was 73.44%, The prevalence rate of dental caries was 30.35%, DMFT was 0.67±1.18, the ratio of caries fil-ling was 4.45%, and the rate of pit and fissure sealing was 2.36%. From 2015 to 2020, the total eruption rates of the four first permanent molars in children aged 6, 7, and 8 showed a decreasing trend (χ2trend was 385.793, 964.142, and 71.964, respectively, all P<0.05). The prevalence rates of dental caries, DMFT caries filling ratio, and pit and fissure sealing rate in children aged 6-9 increased (χ2trend/Ftrend was 1 115.87, 1 270.53, 1 215.02, 763.48, respectively, all P<0.05). The total eruption rates of the four first permanent molars in suburban counties (75.41%) were higher than those in urban areas (71.90%) (χ2=756.44, P<0.05). The prevalence rates of dental caries, DMFT, filling ratio, and pit and fissure sealing rate in urban areas (34.23%, 0.76±1.24, 4.99%, and 3.75%, respectively) were higher than those in suburban areas (25.39%, 0.55±1.09, 3.50%, and 0.58%, respectively) (χ2 was 4 435.30, 3 922.56, 390.89, and 5 262.76, respectively, P<0.05). The first permanent molar eruption completely rate maxillary (84.96%) was higher than mandible (82.88%) (χ2=1 565.70, P<0.05), and the dental caries risk of the mandible (26.07%) was higher than that of the upper (13.88%) (χ2=38 112.53, P<0.05). CONCLUSIONS: The health status of the first permanent molars of children aged 6-9 years in Henan province is not optimistic. The eruption rate decreased, the incidence of caries increased, and the rates of caries filling and pit and fissure sealing were low. We should pay attention to children's eating habits and oral health, strengthen oral health education, and improve oral health awareness.

Effects of different chemical groups on behaviors of bladder cancer cells.

Chemical groups of microenvironment play an important role in the adhesion, proliferation, and apoptosis of tumor cells. The different chemical groups (CH3 , OH, COOH) were grafted on the surfaces with the same density by self-assembly monolayer (SAM) technique to introduce the influence of different microenvironments of the human bladder cancer (5637) cells. The results indicated that the 5637 cells on COOH surface exhibited the lowest proliferation rate and the highest apoptosis rate on the first and fifth day because of negative charge and polarity of the COOH group, which might help optimize biomedicine materials and find new methods to treat bladder cancer.

Tissue-Adhesive Paint of Silk Microparticles for Articular Surface Cartilage Regeneration.

Current biomaterials and tissue engineering techniques have shown a promising efficacy on full-thickness articular cartilage defect repair in clinical practice. However, due to the difficulty of implanting biomaterials or tissue engineering constructs into a partial-thickness cartilage defect, it remains a challenge to provide a satisfactory cure in joint surface regeneration in the early and middle stages of osteoarthritis. In this study, we focused on a ready-to-use tissue-adhesive joint surface paint (JS-Paint) capable of promoting and enhancing articular surface cartilage regeneration. The JS-Paint is mainly composed of N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide (NB)-coated silk fibroin microparticles and possess optimal cell adhesion, migration, and proliferation properties. NB-modified silk fibroin microparticles can directly adhere to the cartilage and form a smooth layer on the surface via the photogenerated aldehyde group of NB reacting with the -NH2 groups of the cartilage tissue. JS-Paint treatment showed a significant promotion of cartilage regeneration and restored the smooth joint surface at 6 weeks postsurgery in a rabbit model of a partial-thickness cartilage defect. These findings revealed that silk fibroin can be utilized to bring about a tissue-adhesive paint. Thus, the JS-Paint strategy has some great potential to enhance joint surface regeneration and revolutionize future therapeutics of early and middle stages of osteoarthritis joint ailments.

Intelligent Detection Platform for Simultaneous Detection of Multiple MiRNAs Based on Smartphone.

As a marker of malignant tumors, miRNA is closely related to the occurrence and metastasis of tumors. How to achieve rapid and sensitive real-time detection is important for clinical prevention and treatment of cancer. In this study, an intelligent detection platform based on smartphone image processing technology made point-of-care testing a reality. This new smart approach could detect multiple targets simultaneously and sensitively. Hydrogel microparticles of different coding modes (shapes, numbers) were prepared by flow lithography to detect different miRNAs. After sandwich immunoassays, different shapes of hydrogels showed different fluorescence intensities depending on their targets. Images were captured by a smartphone and then analyzed by image recognition processing software installed on the smartphone. The concentration of miRNA was obtained within 10 s. The entire reaction process did not exceed 2 h. This intelligent and portable detection platform for miRNAs was reliable and the limit of detection reached the femtomole level. This work provided a demonstration of intelligent, portable, real-time detection of tumor markers.

A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds.

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

Microfabricated silicon nitride membranes for hepatocyte sandwich culture.

We have developed a hepatocyte sandwich culture with improved mass transport properties based on ultra-thin microfabricated porous silicon nitride (Si(3)N(4)) membranes. The dimensions and uniformity of the membrane pores can be configurable, which confers more control over the mass transport. Instead of collagen gels used in conventional sandwich culture, we utilized galactose ligands immobilized on the Si(3)N(4) membranes to support hepatocyte attachment and function in the sandwich culture. Diffusion studies using FITC-dextrans confirmed that mass transport of the microfabricated Si(3)N(4) membrane based sandwich was significantly better than conventional collagen gel sandwich and can be configured by varying the porosity of the Si(3)N(4) membrane. Hepatocytes cultured in the microfabricated Si(3)N(4) membrane based sandwich culture exhibited earlier apical repolarization and biliary excretion, improved differentiated functions and enhanced drug sensitivity compared to hepatocytes cultured in a collagen gel sandwich. The Si(3)N(4) membrane based sandwich culture allows for a systematic optimization of the mass transport properties of hepatocyte culture by changing the pore size and inter-pore distance. This will enable more effective drug testing applications where optimal mass transport is required for hepatocyte function maintenance and drug accessibility.

A Gelatin-sulfonated Silk Composite Scaffold based on 3D Printing Technology Enhances Skin Regeneration by Stimulating Epidermal Growth and Dermal Neovascularization.

One of the key problems hindering skin repair is the deficiency of dermal vascularization and difficulty of epidermis regeneration, which makes it challenging to fabricate scaffolds that can biologically fulfill the requirements for skin regeneration. To overcome this problem, three-dimensional printing was used to fabricate a gelatin-sulfonated silk composite scaffold that was incorporated with basic fibroblast growth factor 2 (FGF-2) through binding with a sulfonic acid group (SO3) (3DG-SF-SO3-FGF). The efficacy and mechanism by which the 3DG-SF-SO3-FGF scaffolds promote skin regeneration were investigated both within in vitro cell culture and in vivo with a full-thickness skin defect model. The histological results showed that the gelatin-sulfonated silk composite scaffolds promoted granulation, and that incorporation of FGF-2 significantly enhanced the regeneration of skin-like tissues after implantation in rat skin defects for 14 and 28 days. Further investigations demonstrated that 3DG-SF-SO3-FGF scaffolds might stimulate dermal vascularization. These findings thus suggest that incorporation of FGF-2 into the 3D printed scaffolds is a viable strategy for enhancing skin regeneration.

Bi-layer collagen/microporous electrospun nanofiber scaffold improves the osteochondral regeneration.

An optimal scaffold is crucial for osteochondral regeneration. Collagen and electrospun nanofibers have been demonstrated to facilitate cartilage and bone regeneration, respectively. However, the effect of combining collagen and electrospun nanofibers on osteochondral regeneration has yet to be evaluated. Here, we report that the combination of collagen and electrospun poly-l-lactic acid nanofibers synergistically promotes osteochondral regeneration. We first fabricated bi-layer microporous scaffold with collagen and electrospun poly-l-lactic acid nanofibers (COL-nanofiber). Mesenchymal stem cells were cultured on the bi-layer scaffold and their adhesion, proliferation and differentiation were examined. Moreover, osteochondral defects were created in rabbits and implanted with COL-nanofiber scaffold. Cartilage and subchondral bone regeneration were evaluated at 6 and 12weeks after surgery. Compared with COL scaffold, cells on COL-nanofiber scaffold exhibited more robust osteogenic differentiation, indicated by higher expression levels of OCN and runx2 genes as well as the accumulation of calcium nodules. Furthermore, implantation of COL-nanofiber scaffold seeded with cells induced more rapid subchondral bone emergence, and better cartilage formation, which led to better functional repair of osteochondral defects as manifested by histological staining, biomechanical test and micro-computed tomography data. Our study underscores the potential of using the bi-layer microporous COL-nanofiber scaffold for the treatment of deep osteochondral defects.

Incorporation of bioactive polyvinylpyrrolidone-iodine within bilayered collagen scaffolds enhances the differentiation and subchondral osteogenesis of mesenchymal stem cells.

Polyvinylpyrrolidone-iodine (Povidone-iodine, PVP-I) is widely used as an antiseptic agent for lavation during joint surgery; however, the biological effects of PVP-I on cells from joint tissue are unknown. This study examined the biocompatibility and biological effects of PVP-I on cells from joint tissue, with the aim of optimizing cell-scaffold based joint repair. Cells from joint tissue, including cartilage derived progenitor cells (CPC), subchondral bone derived osteoblast and bone marrow derived mesenchymal stem cells (BM-MSC) were isolated. The concentration-dependent effects of PVP-I on cell proliferation, migration and differentiation were evaluated. Additionally, the efficacy and mechanism of a PVP-I loaded bilayer collagen scaffold for osteochondral defect repair was investigated in a rabbit model. A micromolar concentration of PVP-I was found not to affect cell proliferation, CPC migration or extracellular matrix production. Interestingly, micromolar concentrations of PVP-I promote osteogenic differentiation of BM-MSC, as evidenced by up-regulation of RUNX2 and Osteocalcin gene expression, as well as increased mineralization on the three-dimensional scaffold. PVP-I treatment of collagen scaffolds significantly increased fibronectin binding onto the scaffold surface and collagen type I protein synthesis of cultured BM-MSC. Implantation of PVP-I treated collagen scaffolds into rabbit osteochondral defect significantly enhanced subchondral bone regeneration at 6 weeks post-surgery compared with the scaffold alone (subchondral bone histological score of 8.80±1.64 vs. 3.8±2.19, p<0.05). The biocompatibility and pro-osteogenic activity of PVP-I on the cells from joint tissue and the enhanced subchondral bone formation in PVP-I treated scaffolds would thus indicate the potential of PVP-I for osteochondral defect repair.

[Biomechanical study of vertebroplasty with geneX(®) cement augmentation in a calf osteoporotic vertebral compression fracture model].

OBJECTIVE: To evaluate the biomechanical properties of geneX cements for use in vertebroplasty in a calf osteoporotic vertebral compression fracture model. METHODS: Thirty vertebral bodies (T(9)-L(4)) were harvested from 4 fresh calf spines. The bone mineral density was measured with dual-energy radiographic absorption. Osteoporotic vertebral model was induced in each vertebra using decalcifying chemical agents, and was then compressed to determine their initial strength and stiffness before injecting the cement. Thirty vertebral bodies were divided randomly into geneX(®) cement group, CSC group, and PMMA group. The fractures were repaired using a transpedicular injection of cements and re-compressed to measure posttreatment strength and stiffness. RESULTS: The normal mean BMD of the calf vertebra was 1.425∓0.072 g/cm(2), which was reduced significantly to 1.074∓0.065 g/cm(2) after decalcification. The mean injected volume was similar between geneX(®) (4.5∓0.7 ml), CSC (4.3∓0.8 ml) and PMMA (3.8∓0.4 ml) groups. The vertebral strength was restored after the treatment to 1198∓529 N in geneX(®) group, 1212∓430 N in CSC group and 1672∓704 N in PMMA group. All the cements produced significantly greater strength than the initial strength (P<0.05). The augmented strength in geneX(®) and CSC groups were similar (P>0.05), but both were significantly less than that in PMMA group (P<0.05). The stiffness in geneX(®), CSC, and PMMA groups was 233∓130, 242∓191, and 323∓145 N/mm, respectively, showing no significant difference between them (P>0.05). No significant difference was found in the augmented stiffness among the 3 cements (P>0.05). CONCLUSION: geneX(®) cement is a useful alternative to PMMA in vertebroplasty for osteoporotic vertebral compression fractures, but further study is needed to evaluate its biosorption in vivo.