Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo.Statement of Significance•The designed wound dressing combines the advantage of natural polysaccharide and polypeptide.•The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis.•The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.

Copper intrauterine device is one of the most adopted contraceptive methods with high effectiveness (over 99 %), low cost, spontaneous reversibility and long-lasting usage. However, the side effects induced from the initial burst release of copper ions (Cu2+) hinder the continuation of the Cu-IUD made of Coarse-Grained Copper (CG Cu). We proposed to tailor the bio-corrosion behaviors of better control of Cu2+ release via the addition of bioactive Mg into the Ultra-Fine Grained (UFG) Bulk Cu. Thus, UFG bulk Cu with 0.4 wt.% Mg was produced via equal-channel angular pressing. The microstructures of the UFG Cu-0.4Mg was observed using electron backscatter diffraction and transmission electron microscopy techniques. The in vitro long-term corrosion behaviors in simulated uterine fluid, cytotoxicity to four cell lines, in vivo biocompatibility and contraceptive efficacy were all studied on CG Cu, UFG Cu and UFG Cu-0.4Mg materials. The results demonstrate that both the ultrafine grains and the addition of bioactive Mg into Cu contribute to the suppression of the burst release of Cu2+ in the initial stage and the maintenance of high level Cu2+ in long-term release. Moreover, the UFG Cu-0.4Mg also exhibited much improved cell and tissue biocompatibility from both the in vitro and in vivo evaluations. Therefore, the contraceptive efficacy of UFG Cu-0.4Mg is still maintained as high as the CG Cu and UFG Cu while the side effects are significantly eased, suggesting the high potential of the UFG Cu-0.4Mg alloy as a new upgrading or alternative material for Cu-IUD. Statement of significance The side effects from burst release of Cu2+ at the initial implantation stage of Cu-containing intrauterine devices (Cu-IUD) is one of the main drawbacks of these devices. In this work, an ultra-fine-grained Cu (UFG Cu) alloyed with a low amount of bioactive Mg was used for a Cu-IUD. The UFG Cu-0.4Mg alloy exhibited suppressed burst release of Cu2+ at initial implantation, while active Cu2+ release for long-term usage was maintained, comparable to coarse-grained pure Cu. Furthermore, the UFG Cu-0.4Mg alloy displayed significantly improved biocompatibility with human uterus cells and a much decreased inflammatory response within the uterus. Therefore, the side effects from Cu-IUD were eased, while high antifertility efficacy of the UFG Cu-0.4Mg alloy was maintained. The UFG Cu-0.4Mg alloy is promising for Cu-IUD. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Significant advances have been achieved in the research evaluating Zn and its alloys as degradable metallic biomaterials mainly for application in bone and blood vessels. In the present study, the degradation behaviors of Zn-0.1Li and Zn-0.8Mg alloys in simulated uterine fluid (SUF) were systematically investigated for 300 days. In vitro viability assays were conducted in different uterine cells (HUSMCs, HEECs, and HESCs), and histological examination after the in vivo implantation into the uterine cavity was performed using pure Zn as control. The immersion test results indicated that both Zn-0.1Li and Zn-0.8Mg alloys exhibited better corrosion resistance than pure Zn, with Zn3(PO4)2⋅4H2O and CaZn2(PO4)2⋅2H2O being the main corrosion products detected in the SUF in addition to ZnO. The cell cytotoxicity assays revealed that Zn-0.1Li and Zn-0.8Mg exhibited better cytocompatibility than Zn. Moreover, the in vivo experiments demonstrated that the Zn-0.1Li and Zn-0.8Mg alloys induced less inflammation in the uterine tissue than pure Zn, with CaCO3 and Zn(HPO4)⋅3H2O being the major biocorrosion products in addition to ZnO. According to these results, zinc alloys appear to be suitable potential candidate materials for future intrauterine biomedical devices.

目的 研究血管生成素样蛋白8(ANGPTL8)在着床后雌激素缺乏下对胎盘和人脐静脉内皮细胞(HUVECs)功能的影响.方法 在大鼠妊娠6.5 d～8.5 d(GD 6.5～GD 8.5)时按照每只0.16 mg·kg-1·d-1的剂量给实验组(n=20)灌胃来曲唑建立着床后短暂雌激素缺乏模型,对照组(n=20)予以相同剂量的5％ 羧甲基纤维素钠.在GD 8.5和GD 19.5时分别取胚胎着床点组织和胎盘组织.,使用Real-time PCR检测组织中Angptl8 mRNA的表达、Western blot检测组织中ANGPTL8蛋白的表达;HUVECs培养在含不同浓度(0、1、2、4、8 nmol/L)的重组ANGPTL8的培养液中,使用划痕实验检测HUVECs的迁移功能、Transwell实验检测HUVECs的侵袭功能、成管实验检测HUVECs的成管功能.结果(1)在GD 8.5时,实验组着床点Angptl8 mRNA的表达水平显著高于对照组(P<0.05),而在GD 19.5时两组间胎盘组织Angptl8 mRNA的表达无显著差异(P>0.05).在GD 8.5和GD 19.5两个时间点实验组着床点和胎盘组织中ANGPTL8蛋白的表达水平均显著高于对照组(P<0.05).(2)细胞实验发现,ANGPTL8对HUVECs的迁移、侵袭和成管产生了抑制作用,并呈现浓度依赖性(P<0.05).结论 大鼠胚胎着床后短暂雌激素缺乏后胎盘ANGPTL8的上调抑制胎盘血管内皮的正常功能.

目的 探索在胚胎着床后短暂抑制雌激素合成对大鼠孕晚期胎盘和胎盘生长因子的影响.方法 在大鼠妊娠6.5～8.5 d(GD 6.5～8.5)时给予0.16 mg·kg-1·d-1剂量的来曲唑灌胃(实验组,n=5)和溶媒灌胃(对照组,n=5),在GD 19.5取材,观察胎盘组织学形态,并利用实时荧光定量聚合酶链式反应(RT-qPCR)、蛋白质印迹法(Western Blot)和免疫组织化学方法(IHC)检测胎盘生长因子(PlGF)的表达.结果 在GD 19.5时,实验组胎盘重量较对照组显著增加[(0.788±0.101)g v s.(0.462±0.040)g,P<0.01],胎盘连接区滋养层巨细胞增多伴少量纤维素样沉积,迷路区绒毛间隙加大,血窦大小不一.RT-qPCR、Western Blot和IHC结果显示实验组胎盘Plgf mRNA的表达量相较于对照组显著升高(P<0.01),PlGF蛋白表达也显著升高(P<0.01),主要表达在连接区滋养层巨细胞和迷路区滋养层细胞.结论 大鼠胚胎着床后给予来曲唑短暂抑制雌激素合成可导致孕晚期胎盘肥大并促使PlG F表达升高,提示孕早期雌激素水平降低影响孕晚期胎盘功能.

Magnesium and its alloys were widely investigated in many body fluid microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine microenvironment. In this study, the degradation behaviors of HP-Mg, Mg-1Ca, and Mg-2Zn alloys in simulated uterine fluid (SUF) were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the gluteal muscle of rat was used as the implantation position to study the in vivo biocompatibility as a mimic of the intrauterine device (IUD) fixation part. The 120-day immersion test indicated that the Mg-1Ca alloy had a faster degradation rate than the Mg-2Zn alloy and HP-Mg and dissolved entirely in the SUF. Indirect cytotoxicity assay showed that the extracts of HP-Mg, Mg-1Ca, and Mg-2Zn alloys have positive effects on human uterine smooth muscle cells (HUSMC), human endometrial epithelial cells (HEEC), and human endometrial stromal cells (HESC), especially for the Mg-1Ca alloy group. Furthermore, the in vivo experiment showed that HP-Mg, Mg-1Ca, and Mg-2Zn alloy implants cause a light inflammatory response in the initial 3 days, but they were surrounded mainly by connective tissue, and lymphocytes were rarely observed at 4 weeks. Based on the above facts, we believed that it is feasible for using biomedical Mg alloys in obstetrics and gynecology and proposed three kinds of medical device candidates for future R&D. Statement of Significance Magnesium alloys were widely investigated in various body microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine environment. In this work, the degradation behaviors of Mg alloys in simulated uterine fluid were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the tibialis anterior of a rat model was used as the implantation position to study the in vivo biocompatibility. The comprehensive in vitro and in vivo testing results indicated that biomedical Mg alloys are feasible for use in obstetrics and gynecology. Further, three kinds of medical device candidates were proposed. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.