Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway.

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1-34), we previously designed a novel PTH analog, PTH(3-34)(29-34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA-MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.

Corrosion Resistance and Mechanical Properties of Cr-Rich 316 Stainless Steel Coatings Fabricated by the TIG Process Using Flux-Cored Wires.

Arc welded 316 stainless steel coatings with flux-cored wires are very promising for marine service environments due to their low cost, high efficiency, and satisfactory performance, while they suffers from Cr dilution during the preparation process. Herein, based on the consideration of increasing the Cr content and ensuring the same value of the Cr/Ni equivalence ratio (Creq/Nieq), 316-modified flux-cored wires, 316F (19Cr-12Ni-3Mo) and 316G (22Cr-14Ni-3Mo), were designed under the guidance of a Schaeffler diagram for the improvement of the electrochemical and mechanical properties of 316 stainless steel coatings. The designed flux-cored wires were welded into a three-layer cladding by the tungsten inert gas welding (TIG) process, and the microstructure, corrosion resistance, and mechanical properties of the claddings were investigated. The results showed that 316F and 316G consist of γ-Fe (austenite) and a small portion of δ-Fe (ferrite) as the Creq/Nieq is approximately 1.5. However, due to the higher value of the equivalent Cr content (ECC), 316G has an additional intermetallic phase (σ), which precipitates as a strengthening phase at grain boundaries, significantly increasing the tensile and yield strength of 316G but reducing its plasticity. In addition, the corrosion current density (icorr) and pitting potential (Eb) for 316G are 0.20447 µA·cm-2 and 0.634 V, respectively, while the values for 316F are 0.32117 µA·cm-2 and 0.603 V, respectively, indicating that 316G has better anti-corrosion performance.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Human Parathyroid Hormone Analog (3-34/29-34) promotes wound re-epithelialization through inducing keratinocyte migration and epithelial-mesenchymal transition via PTHR1-PI3K/AKT activation.

BACKGROUND: Re-epithelialization is important in the process of wound healing. Various methods have been identified to expedite the process, but their clinical application remains limited. While parathyroid hormone (PTH) has shown promising results in wound healing due to its role in promoting collagen deposition and cell migration, application is limited by its potentially inhibitive effects when being continuously and locally administrated. Herein, we developed a novel PTH analog, Human parathyroid hormone (hPTH) (3-34/29-34) (henceforth MY-1), by partially replacing and repeating the amino acid sequences of hPTH (1-34), and evaluated its effect on skin wound re-epithelialization. METHODS: CCK-8, colony formation unit assay, and Ki67 immunofluorescent staining were performed to evaluate the effect of MY-1 on HaCaT cell proliferation. Then, wound scratch assay, Transwell assay and lamellipodia staining were carried out to evaluate the effect of MY-1 on cell migration. Moreover, the epithelial-mesenchymal transition (EMT) markers were measured using qPCR and western blot analysis. For in-vivo drug delivery, gelatin methacryloyl (GelMA) hydrogel was employed to load the MY-1, with the physicochemical characteristics evaluated prior to its application in wound models. Then, MY-1's role in wound healing was determined via acute skin wound models. Finally, the mechanism that MY-1 activated was also detected on HaCaT cells and in-vivo wound models. RESULTS: In-vitro, MY-1 accelerated the migration and EMT of HaCaT cells, while having little effect on cell proliferation. GelMA and MY-1-incorporated GelMA hydrogels showed similar physicochemical characteristics and were used in the in-vivo studies, where the results revealed that MY-1 led to a stronger re-epithelialization by inducing basal keratinocyte migration and EMT. Further studies on in-vivo wound models and in-vitro HaCaT cells revealed that MY-1 regulated cell migration and EMT through activating PI3K/AKT signaling. The parathyroid hormone type 1 receptor (PTHR1), the main receptor of PTH, was found to be the upstream of PI3K/AKT signaling, through interfering PTHR1 expression with a small interference RNA following detection of the PI3K/AKT activation. CONCLUSION: Collectively, our study demonstrated that MY-1 accelerates skin wound re-epithelialization by inducing keratinocyte migration and EMT via PTHR1-PI3K/AKT axis activation. Video Abstract.

Research on Underwater Wet Laser Self-Fusion Welding Process and Analysis of Microstructure and Properties of TC4 Titanium Alloy Weld.

In order to explore the feasibility of underwater wet laser welding of the TC4 titanium alloy, research on the underwater laser self-fusion welding process was carried out. The weld structure and mechanical properties in both the air environment and the underwater environment were compared and analyzed. The results show that increasing the laser power and reducing the welding speed are beneficial to obtain a larger water depth threshold. Off-focus amount has little effect on water depth threshold; when the laser power is 3000 W and the welding speed is 5 mm/s, and the water depth exceeds 7 mm, a continuous weld cannot be formed. Compared with welding in the air, underwater welding has narrower weld width, smaller heat affected zone and finer crystal grains. The weld structure is mainly composed of α' martensite and secondary acicular α' phase, it is distributed in a net basket shape and the grain size at the top of the weld is finer. The hardness of the weld center is above 600 HV0.1, and the residual stress of the underwater welding weld is approximately symmetrically distributed. There is a large tensile stress along the welding direction at the weld, reaching 458 MPa. The larger residual tensile stress leads to the decrease of weld tensile strength, the tensile strength and elongation of the middle sample are only 52% and 77% of the base metal. Furthermore, the fracture mode is typical brittle fracture.

Investigation on Microstructure and Properties of Duplex Stainless Steel Welds by Underwater Laser Welding with Different Shielding Gas.

Taking S32101 duplex stainless steel as the research object, underwater laser wire filling welding technology was used for U-groove filling welding. The influence of different shielding gas compositions on the ferrite content, microstructure, mechanical properties and pitting corrosion resistance was studied by simulating a water depth of 15 m in the hyperbaric chamber. The results show that, under the same process parameters, the size and proportion of austenite in the weld when using pure nitrogen as the shielding gas are larger than those protected by other shielding gases. In a mixed shielding gas, the increase in nitrogen content has little effect on the strength and toughness of the weld. Regardless of the shielding gas used, the base metal was the weakest part of the weld. At the same time, intermetallic inclusions have an adverse effect on the impact toughness of the weld. The pitting corrosion resistance of the welds depends on the Cr2N content in the heat-affected zone. The precipitation and enrichment of Cr2N causes local chromium deficiency, which is the main factor for the weak pitting corrosion ability of the heat-affected zone. Pure nitrogen protection has a better corrosion resistance than other gas protection.

Microstructure and Corrosion Resistance of Underwater Laser Cladded Duplex Stainless Steel Coating after Underwater Laser Remelting Processing.

Combined with the technologies of underwater local dry laser cladding (ULDLC) and underwater local dry laser remelting (ULDLR), a duplex stainless steel (DSS) coating has been made in an underwater environment. The phase composition, microstructure, chemical components and electrochemical corrosion resistance was studied. The results show that after underwater laser remelting, the phase composition of DSS coating remains unchanged and the phase transformation from Widmanstätten austenite + intragranular austenite + (211) ferrite to (110) ferrite occurred. The ULDLR process can improve the corrosion resistance of the underwater local dry laser cladded coating. The corrosion resistance of remelted coating at 3 kW is the best, the corrosion resistance of remelted coating at 1kW and 5kW is similar and the corrosion resistance of (110) ferrite phase is better than grain boundary austenite phase. The ULDLC + ULDLR process can meet the requirements of efficient underwater maintenance, forming quality control and corrosion resistance. It can also be used to repair the surface of S32101 duplex stainless steel in underwater environment.

Microstructure and Mechanical Properties of Wire Arc Additively Manufactured MoNbTaWTi High Entropy Alloys.

High-temperature resistant high-entropy alloys (HEAs) have attracted extensive attention due to their excellent thermodynamic stability and mechanical properties, especially at high temperatures. However, a highly effective method for large-size HEAs is still desirable but challengeable. This research reported a facile yet effective strategy for MoNbTaWTi HEAs via in-situ wire arc additive manufacturing (WAAM). The wire was MoNbTaWTi cable-type welding wire (CTWW) consisting of one center wire and seven twisted peripheral wires. Then, additive manufacturing of MoNbTaWTi high entropy alloys (HEAs) was accomplished, and various analytical techniques studied the microstructures and mechanical properties of the overlaying formed layers. X-ray diffraction showed the overlaying formed layers to contain a single disordered BCC solid solution phase with high-temperature structural stability. In addition, the single-phase BCC structure was maintained from 0 to 1400 °C. The bottom of the overlaying formed layers was made of columnar cellular structure, and the upper part resembled "cauliflower-like" fine dendrite and equiaxed crystal structure. The hardness of the overlaying formed layers averaged 533 HV0.2 at room temperature. At 1000 °C, the hardness was around 110 HV1, close to the value of Inconel 718 alloy (125 HV1). The compressive strength of the overlaying formed alloy layers displayed no sensitivity towards change in temperature from 500 to 1000 °C. As the temperature rose from 500 to 1000 °C, the compressive strength changed from 629 to 602 MPa, equivalent to only a 27 MPa decrease. The latter was much higher than the strength of Inconel 718 alloy at the same temperature (200 MPa).

Elasto-Plastic Fracture Mechanics Analysis of the Effect of Shot Peening on 300M Steel.

A modified J-integral calculation method is adopted to fix the problem of the quantitative evaluation of the crack propagation of shot-peened structures. Considering the residual stress, residual strain, and residual strain energy, the effect of shot peening on the J-integral parameters of semi-elliptic surface crack fronts is quantitatively calculated and a method is provided for the performance evaluation of the shot peening layer. First, the shot peening process is simulated, then the fatigue crack is generated by changing the constraint condition and a far-field load is applied to calculate the J-integral parameters, crack propagation rate, and crack kinking angle. The effects of different crack depths and shot velocities on the fracture parameters are analyzed. The results show that the reduction in the J-integral value after shot peening decreases with the increase in the crack depth when the shot velocity is a certain value, which indicates that shot peening is more beneficial for suppressing the fatigue crack propagation. When the crack depth is greater than the depth of the compressive stress layer, shot peening accelerates the crack propagation. The reduction in the J-integral value decreases with the increase in shot velocity when the crack depth is a certain value; therefore, increasing shot velocity is more beneficial for retarding fatigue crack propagation.