Revisiting matrix hydrogel composed of gelatin and hyaluronic acid and its application in cartilage regeneration.

With the increasing incidence of knee osteoarthritis (KOA), the reparation of cartilage defects is gaining more attention. Given that tissue integration plays a critical role in repairing cartilage defects, tissue adhesive hydrogels are highly needed in clinics. We constructed a biomacromolecule-based bioadhesive matrix hydrogel and applied it to promote cartilage regeneration. The hydrogel was composed of methacrylate gelatin and N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitroso) butyl amide modified hyaluronic acid (HANB). The methacrylate gelatin provided a stable hydrogel network as a scaffold, and the HANB served as a tissue-adhesive agent and could be favorable for the chondrogenesis of stem cells. Additionally, the chemically modified HA increased the swelling ratio and compressive modulus of the hydrogels. The results of our in vitro study revealed that the hydrogel was compatible with bone marrow stromal cells. In vivo, the hyaluronic-acid-containing hydrogels were found to promote articular cartilage regeneration in the defect site. Therefore, this biomaterial provides promising potential for cartilage repair.

Chondroitin Sulfate Improves Mechanical Properties of Gelatin Hydrogel for Cartilage Regeneration in Rats.

Cartilage injury is a common disease in daily life. Especially in aging populations, the incidence of osteoarthritis is increasing. However, due to the poor regeneration ability of cartilage, most cartilage injuries cannot be effectively repaired. Even cartilage tissue engineering still faces many problems such as complex composition and poor integration of scaffolds and host tissues. In this study, chondroitin sulfate, one of the main components of extracellular matrix (ECM), is chosen as the main natural component of the material, which can protect cartilage in a variety of ways. Moreover, the results show that the addition of chondroitin sulfate improves the mechanical properties of gelatin methacrylate (GelMA) hydrogel, making it able to effectively bear mechanical loads in vivo. Further, chondroitin sulfate is modified to obtain the oxidized chondroitin sulfate (OCS) containing aldehyde groups via sodium periodate. This special group improves the interface integration and adhesion ability of the hydrogel to host cartilage tissue through schiff base reactions. In summary, GelMA/OCS hydrogel is a promising candidate for cartilage regeneration with good biocompatibility, mechanical properties, tissue integration ability, and excellent cartilage repair ability.

[Effect and Persistent Effect of Thiolated Montmorillonite on Safe Production in Cadmium-contaminated Cropland].

To explore the effect and persistent effect of thiolated montmorillonite (TM) on safe production in cadmium (Cd) contaminated cropland, a two-year field experiment was conducted with different application amounts of TM. By adding to highly contaminated soils containing 2.46-3.81 mg·kg-1 Cd with no replenishment, the impacts of TM on concentrations of Cd in different parts of rice and available Cd in soils were investigated. The results showed that TM could significantly reduce the contents of Cd in brown rice as well as the contents and proportions of available Cd in soils, and its persistent effects on the passivation of Cd were obvious. After applying 0.5% or 1% TM to soils, the contents of Cd in different parts of the rice decreased significantly in the first season compared with that in the control. The contents of Cd in brown rice in the first season decreased to 0.16 mg·kg-1 and 0.08 mg·kg-1, respectively, by 84.0% and 91.9% compared with that of the control (0.98 mg·kg-1). Contents of Cd in brown rice were significantly lower than the maximum allowable amount (0.2 mg·kg-1) set by China (GB 2762-2017). Under the 0.5% and 1% treatments, the contents of Cd in brown rice of the subsequent three seasons under successive planting decreased by 50.2%-67.8% and 56.0%-81.6%, respectively, which were within the allowable amount. The proportions of available Cd in soils in the first season decreased from 48.4% under the control to 27.9% and 18.4%, respectively, which decreased by 20.5% and 29.9% under the 0.5% and 1% treatments. Compared with that in the control, proportions of available Cd in soils of the following three seasons decreased by 10.0%-17.1% and 12.4%-20.8%. There was a significant positive correlation between available Cd contents in soils and Cd contents in various parts of the rice. TM mainly reduced available Cd contents in soils, then reduced the absorption and accumulation of Cd in rice. The results of the two-year field experiment showed significant and continuous effects of TM on inhibiting Cd uptake by rice, which could be applied to the safe production in heavily Cd contaminated cropland.

Enhancing autophagy and energy metabolism in the meniscus can delay the occurrence of PTOA in ACLT rat.

Osteoarthritis (OA) is a progressive degenerative joint disease characterized by the destruction of the articular cartilage, meniscus and the like. Autophagy and cellular energy metabolism are the mechanisms by which cells maintain homeostasis. However, little is known about the effects of autophagy and cellular energy metabolism on meniscus degeneration, and the pathogenesis of posttraumatic osteoarthritis (PTOA) after the meniscal injury is rarely reported. Therefore, this study aimed to investigate the relationship between changes in autophagy and cellular energy metabolism in the meniscus following anterior cruciate ligament transection (ACLT) and PTOA induced by subsequent articular cartilage injury. In this study, we use a combination of cell experiments in vitro and animal experiments in vivo. On the one hand, cell experiment results show that inhibiting the mTORC1 signaling pathway by inhibiting the phosphorylation of S6K and AKT proteins in meniscal cells will lead to the increase of Beclin1, LC-3B, ATG12, ULK1, P62, and activate autophagy-related signaling pathways, which in turn protects the extracellular matrix component COL1 of meniscal cells from degradation by catabolic factor MMP13. In addition, it increased the generation of mitochondrial membrane potential in meniscal cells, increased the expression of anti-apoptotic factor BCL-XL, decreased the expression of pro-apoptotic factors BAD and BAX, and reduced the apoptosis of meniscal cells. More importantly, under the stimulation of inflammatory factor IL-1ß, the secretion of meniscus cells can reduce the elevated levels of MMP13 and Adamts5 caused by chondrocytes affected by IL-1ß. On the other hand, the results of animal experiments in vivo further proved the validity of the results of the cell experiments, and also proved that the meniscus injury did prior to the articular cartilage degeneration after ACLT. In conclusion, this study suggests that the meniscus prior to articular cartilage damage during the development of PTOA after ACLT, and that promoting autophagy and energy metabolism of meniscal cells may be a potential therapeutic target for delaying PTOA.

Mesenchymal Stem Cells-Hydrogel Microspheres System for Bone Regeneration in Calvarial Defects.

The repair of large bone defects in clinic is a challenge and urgently needs to be solved. Tissue engineering is a promising therapeutic strategy for bone defect repair. In this study, hydrogel microspheres (HMs) were fabricated to act as carriers for bone marrow mesenchymal stem cells (BMSCs) to adhere and proliferate. The HMs were produced by a microfluidic system based on light-induced gelatin of gelatin methacrylate (GelMA). The HMs were demonstrated to be biocompatible and non-cytotoxic to stem cells. More importantly, the HMs promoted the osteogenic differentiation of stem cells. In vivo, the ability of bone regeneration was studied by way of implanting a BMSC/HM system in the cranial defect of rats for 8 weeks. The results confirmed that the BMSC/HM system can induce superior bone regeneration compared with both the HMs alone group and the untreated control group. This study provides a simple and effective research idea for bone defect repair, and the subsequent optimization study of HMs will provide a carrier material with application prospects for tissue engineering in the future.

The application of platelet-rich plasma in the treatment of knee osteoarthritis: A literature review.

BACKGROUND: Primary knee osteoarthritis remains a difficult-to-control degenerative disease. With the rise in average life expectancy and the incidence of obesity, osteoarthritis has brought an increasing economic and physical burden on people. This article summarizes the latest understanding of platelet-rich plasma in the treatment of knee osteoarthritis, and reviews the economic issues of PRP. METHODS: The literatures in Pubmed, Embase, Cochrane library, Web-science and other databases were searched, and literature inclusion and exclusion criteria were formulated. According to the Cochrane systematic reviewer's manual, the included literatures were grouped, and qualitative descriptions and quantitative meta-analysis were performed. Continuous statistical methods were used to compare the effects and adverse effects of PRP before and after treatment, as well as between PRP and other conservative treatments. RESULTS: A total of 12 randomized controlled trials were included in this study. A total of 959 KOA patients (1070 knees) were enrolled and followed for 3-12 months. PRP total knee scores were significantly better than baseline at 1, 2, 3, 6 and 12 months after treatment (1 month: SMD = 0.60, P < 0.01; 2 months: SMD = 0.98, P < 0.01; 3 months: SMD = 1.16, P < 0.01; 6 months: SMD = 1.49, P < 0.01; 12 months: SMD = 1.47, P < 0.01). In terms of adverse reactions, PRP did not increase the risk of adverse events compared with HA (OR = 0.96, P = 0.85). CONCLUSIONS: Compared with many other treatment methods, intra-articular injection of PRP has been proven to be safe and effective to improve the quality of life of patients with KOA.

TCP/PLGA composite scaffold loaded rapamycin in situ enhances lumbar fusion by regulating osteoblast and osteoclast activity.

The purpose of this study was to develop a novel ß-tricalcium phosphate (TCP)/poly (D,L-lactic-co-glycolic acid) (PLGA) composite scaffold loaded with rapamycin that can regulate the activity of osteoblasts and osteoclasts for lumbar fusion. The TCP/PLGA composite scaffold was fabricated by cryogenic three-dimensional printing techniques and then loaded with rapamycin in situ. The structural surface morphology of the composite scaffold was tested with scanning electron microscope. To evaluate the biocompatibility of the composite scaffold in vitro, bone marrow mesenchymal stem cells (BMSCs) were cultured on the TCP/PLGA composite scaffold slide and tested with Live/Dead Viability Kit. The effect of rapamycin on osteoclast and osteoblast was studied with staining and Western blotting. The in vitro results showed that the rapamycin-loaded TCP/PLGA composite scaffold showed good biocompatibility with BMSC and released rapamycin obviously promoted the osteoblast differentiation and mineralization. In vivo study, the TCP/PLGA composite scaffold loaded with rapamycin were implanted in lumbar fusion model and study with micro-computed tomography scanning, hematoxylin-eosin, Masson, and immune-histological staining, to evaluate the effect of rapamycin on bone fusion. The in vivo results demonstrated that rapamycin-loaded TCP/PLGA composite scaffold could enhance bone formation by regulating osteoblast and osteoclast activity, respectively. In this study, the TCP/PLGA composite scaffold loaded with rapamycin was confirmed to provide great compatibility and improved performance in lumbar fusion by regulating osteoblastic and osteoclastic activity and would be a promising composite biomaterial for bone tissue engineering.

Cryogenic 3D printing of porous scaffolds for in situ delivery of 2D black phosphorus nanosheets, doxorubicin hydrochloride and osteogenic peptide for treating tumor resection-induced bone defects.

Tumor resection is widely used to prevent tumor growth. However, the defected tissue at the original tumor site also causes tissue or organ dysfunction which lowers the patient's life quality. Therefore, regenerating the tissue and preventing tumor recurrence are highly important. Herein, according to the concept of 'first kill and then regenerate', a versatile scaffold-based tissue engineering strategy based on cryogenic 3D printing of water-in-oil polyester emulsion inks, containing multiple functional agents, was developed, in order to realize the elimination of tumor cells with recurrence suppression and improved tissue regeneration sequentially. To illustrate our strategy, water/poly(lactic-co-glycolic acid)/dichloromethane emulsions containing ß-tricalcium phosphate (ß-TCP), 2D black phosphorus (BP) nanosheets, low-dose doxorubicin hydrochloride (DOX) and high-dose osteogenic peptide were cryogenically 3D printed into hierarchically porous and mechanically strong nanocomposite scaffolds, with multiple functions to treat bone tumor, resection-induced tissue defects. Prompt tumor ablation and long-term suppression of tumor recurrence could be achieved due to the synergistic effects of photothermotherapy and chemotherapy, and improved bone regeneration was obtained eventually due to the presence of bony environment and sustained peptide release. Notably, BP nanosheets in scaffolds significantly reduced the long-term toxicity phenomenon of released DOX during in vivo bone regeneration. Our study also provides insights for the design of multi-functional tissue engineering scaffolds for treating other tumor resection-induced tissue defects.