Expression of concern: Poly(lactide-co-glycolide) grafted hyaluronic acid-based electrospun fibrous hemostatic fragments as a sustainable anti-infection and immunoregulation material.

Expression of concern for 'Poly(lactide-co-glycolide) grafted hyaluronic acid-based electrospun fibrous hemostatic fragments as a sustainable anti-infection and immunoregulation material' by Wen Liu et al., J. Mater. Chem. B, 2019, 7, 4997-5010, https://doi.org/10.1039/C9TB00659A.

Controlled release of KGF-2 for regulation of wound healing by KGF-2 complexed with "lotus seedpod surface-like" porous microspheres.

Keratinocyte growth factor-2 (KGF-2) can regulate the proliferation and differentiation of keratinocyte, which plays a remarkable role in maintaining normal tissue structure and promoting wound healing. As an effective strategy, KGF-2 solution is widely used in the treatment of wounds in clinical applications. However, KGF-2 in solution cannot achieve sustained release, which results in drug loss and unnecessary waste. Polysaccharide hemostasis microspheres (PHMs) are an ideal drug loading platform due to their special "lotus seedpod surface-like" morphology and structure. Herein, to realize the controllable release of KGF-2, PHMs loaded with KGF-2 (KGF-2@PHMs) were prepared. It was found that the bioavailability of KGF-2 was improved greatly. Most importantly, KGF-2@PHMs can reduce inflammation and accelerate the wound healing process due to the controlled release of KGF-2. KGF-2@PHMs might be a potential alternative strategy for wound healing in future clinical applications.

lncRNA SNHG10 Promotes the Proliferation and Invasion of Osteosarcoma via Wnt/ß-Catenin Signaling.

Uncontrolled growth and an enforced epithelial-mesenchymal transition (EMT) process contribute to the poor survival rate of patients with osteosarcoma (OS). Long noncoding RNAs (lncRNAs) have been reported to be involved in the development of OS. However, the significant role of lncRNA SNHG1O on regulating proliferation and the EMT process of OS cells remains unclear. In this study, quantitative real-time PCR and fluorescence in situ hybridization (FISH) results suggested that SNHG10 levels were significantly increased in OS compared with healthy tissues. In vitro experiments (including colony formation, CCK-8, wound healing, and transwell assays) and in vivo experiments indicated that downregulation of SNHG10 significantly suppressed the proliferation and invasion of OS cells. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay confirmed that SNHG10 could regulate FZD3 levels through sponging microRNA 182-5p (miR-182-5p). In addition, the SNHG10/miR-182-5p/FZD3 axis could further promote the ß-catenin transfer into nuclear accumulation to maintain the activation of the Wnt singling pathway. Together, our results established that SNHG10 has an important role in promoting OS growth and invasion. By sponging miR-182-5p, SNHG10 can increase FZD3 expression and further maintain the activation of Wnt/ß-catenin singling pathway in OS cells.

Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1.

The epithelial-mesenchymal transition (EMT) is a vital step in osteosarcoma (OS) progression toward metastasis, but the specific molecular events governing this process are incompletely characterized, with miRNAs having increasingly been found to regulate the EMT. In this study, We assessed levels of miR-22 and its target, Twist1, via real-time PCR (qRT-PCR). We further used functional proliferation assays, measures of cell morphology, and western blotting to assess the functional relevance of miR-22 in OS and confirmed Twist1 as a miR-22 target via luciferase reporter assay. We observed a significant decrease in miR-22 levels in OS tumor samples relative to normal tissue, with such downregulating being significantly associated with tumor histological grade. When overexpressed, miR-22 impaired OS cell proliferation and EMT progression. We found Twist1 to be a direct miR-22 target, with levels of miR-22 and Twist1 mRNA being inversely correlated in patient samples. When overexpressed, miR-22 suppressed Twist1 translation and thereby attenuated the EMT in OS cells. These results clearly demonstrate that miR-22 can regulate the EMT in OS cells via targeting Twist1, thus highlighting a potentially novel pathway that can be therapeutically targeted in order to treat OS.

Polysaccharide Based Hemostatic Strategy for Ultrarapid Hemostasis.

Bleeding complications usually cause significant morbidity and mortality in civilian and military populations. In clinical application, hemostatic sponges, gauzes, hydrogel, and bandages are widely used as the traditional effective hemostatic products for hemorrhage. However, the traditional hemostatic devices or agents cannot meet the requirement for treatment of massive bleeding. Therefore, the excellent hemostatic performance of hemostatic products are of great significance for saving lives. Natural polysaccharides, as the main chemical component, have been widely used in the preparation of hemostasis due to their perfect biocompatibility and biodegradability. Polysaccharide based hemostatic products are available in variety of forms, such as, hydrogel, sponges, gauze and microspheres. The purpose of the present review is to report the research progress on polysaccharide hemostatic products and technology.

Polysaccharide-Based Lotus Seedpod Surface-Like Porous Microsphere with Precise and Controllable Micromorphology for Ultrarapid Hemostasis.

Rapid water absorption rate has become a bottleneck that limits ultrarapid hemostatic performance of hemostatic microspheres. Herein, we reported a "lotus seedpod surface-like" polysaccharide hemostatic microsphere (PHM) with "macropits on surface" morphology and "micropores in macropits" structure. Unique macropits on surface can promote the water absorption rate because they are advantageous to quickly guide blood into the micropores. Special micropores are internally connected with each other, which endows PHM4 with high water absorption ratio. During the process of blood entering the micropores from micropits, the pore size decreases gradually. In this way, blood clotting factors could be rapidly concentrated. PHM4 showed the highest water absorption rate (40.7 mL/s/cm2) and rapid hemostatic property in vivo (hemostatic time shortened from 210 to 45 s). Lotus seedpod surface-like PHMs are believed to have further clinical application as an effective hemostasis.

Peptide-immobilized starch/PEG sponge with rapid shape recovery and dual-function for both uncontrolled and noncompressible hemorrhage.

It is challenging for traditional hemostatic sponges to meet the clinic demand for both uncontrolled and noncompressible hemorrhage. With the aim to develop a rapid shape recovery material with both active and passive hemostatic performance, a dual-functional hemostatic sponge (TRAP-Sp) with a macroporous structure and good mechanical properties for controlling massive and noncompressible hemorrhage was prepared by chemically immobilizing thrombin-receptor-agonist-peptide (TRAP) onto a starch/polyethylene glycol (PEG) sponge. The TRAP2-Sp1 showed the best hemostatic performance among all samples in both rat artery uncontrollable hemorrhage and liver defect noncompressible hemorrhage models. When analyzing the hemostatic mechanism of TRAP-Sp, the high water absorption capacity of the sponge contributed to absorbing plasma, concentrating blood cells, and enhancing blood coagulation. After absorbing water, the shape-fixed TRAP-Sp with sufficient mechanical strength and high resilience can rapidly expand and apply pressure to the wound. TRAP immobilized on the sponge could activate the adhered platelets in an active pathway. Additionally, evaluation of cytotoxicity, hemolysis, and histology further highlighted the adequate biocompatibility of TRAP-Sp. With excellent hemostatic performance and biosafety, this sponge could be a potential candidate as a topical hemostatic agent for uncontrolled and noncompressible hemorrhage. STATEMENT OF SIGNIFICANCE: There is a need for innovative hemostatic materials for both uncontrolled and noncompressible hemorrhage. This manuscript describes a rapid shape recovery hemostatic sponge with both active and passive hemostatic performances synthesized by foaming technique, cross-linking reaction, and chemical immobilization of thrombin-receptor-agonist-peptide (TRAP). On contact with blood, the shape-fixed sponge can not only rapidly recover its original shape and concentrate platelets and RBCs but also activate the adhered platelets efficiently. The dual-functional sponge has excellent hemostatic efficacy in rat femoral artery hemorrhage and can control noncompressible hemorrhage in penetrating liver wound. Thus, we believe that this sponge could be a potential candidate as a topical hemostatic agent for uncontrolled and noncompressible hemorrhage.

Poly(lactide-co-glycolide) grafted hyaluronic acid-based electrospun fibrous hemostatic fragments as a sustainable anti-infection and immunoregulation material.

Poly(lactide-co-glycolide) (PLGA) copolymers are promising synthetic materials in the biomedical field. However, in wound management, their hydrophobic properties limit their further application because of their poor adhesion to the surface of moist wounds. Furthermore, the lack of hemostatic materials with sustainable anti-infection and immunoregulation functions remains a highly significant clinical problem, as commercially available hemostatic products, such as Arista™, Celox™ and QuikClot™, do not have sufficient infection prevention and immunoregulation properties. Herein, we employ electrospinning, ammonia dissociation and surface grafting techniques to develop a series of PLGA-based hemostatic materials, including a PLGA electrospun fibrous membrane, PLGA-NH2 fibrous particles and PLGA-hyaluronic acid fibrous fragments (PLGA-HA FFs). Notably, we load azithromycin on the PLGA-HA FFs to endow them with anti-infection and immunoregulation properties. The hemostatic mechanism analysis demonstrates that the PLGA-HA FFs show superior hemostasis performance compared to traditional gauzes. The results show that the PLGA-HA FFs can act as a versatile platform with high encapsulation of azithromycin (83.03% ± 2.81%) and rapid hemostasis (28 ± 2 s) as well as prominent cytocompatibility towards L929 cells, RAW 264.7 cells and red blood cells. We believe that the current research proposes a possible strategy to synthesize materials that achieve not only safe and effective hemostasis, but also have anti-infection and immunoregulation properties for the development of further hemostatic products.

Fabricating antimicrobial peptide-immobilized starch sponges for hemorrhage control and antibacterial treatment.

It is important to control immediate hemorrhage and prevent infection simultaneously in the wound management. However, most of hemostatic materials are associated with low efficiency of hemostasis, poor biocompatibility and lack of antimicrobial properties. A kind of starch-based macroporous sponges (KR-Sps) immobilized covalently with antimicrobial peptide KR12 using highly efficient thiol-ene photo click reaction were developed. The physical properties of these sponges could be fine-tuned by varying the ratio of modified starch/HS-PEG-SH and the polymer concentration. The in vitro and vivo results demonstrated that KR-Sps induced thrombosis, shortened clotting time and reduced the blood loss at bleeding site. Besides, KR12 immobilized sponge exhibited inherent antimicrobial properties against Gram (+) and (-) bacteria and methicillin-resistant Staphylococcus aureus (MRSA), which could maintain at least 5 days. Therefore, KR-Sps were believed to be an excellent candidate as hemostatic and antimicrobial product for the intraoperative wound management.

Tannic Acid Cross-linked Polysaccharide-Based Multifunctional Hemostatic Microparticles for the Regulation of Rapid Wound Healing.

Hemostatic microparticles (HMs) have been widely used in surgery. To improve the comprehensive performance of HMs, multifunctional HMs named HM15 and HM15 ' are prepared from starch, carboxymethyl chitosan, hyaluronic acid, and tannic acid. Herein, tannic acid is used as an effective cross-linker. A 3D network structure for cell growth and wound repair can be formed by secondary cross-linking. Through synergistic effect of these natural materials, the process of wound healing can be regulated controllably. HM15 and HM15 ' have the ability of rapid hemostasis. Moreover, HM15 ' shows excellent properties in antibacteria and wound healing acceleration. Blood clotting time treated with different HMs is shortened obviously from 436.8 s to 126 s. Compared with Celox, HM15 and HM15 ' exhibited better broad spectrum antibacterial activity against both Escherichia coli and Staphylococcus aureus. Notably, the wound can be repaired rapidly by HM15 ' in 14 days. These multifunctional HMs might have an important prospect in clinical application.

Scalable lithography from Natural DNA Patterns via polyacrylamide gel.

A facile strategy for fabricating scalable stamps has been developed using cross-linked polyacrylamide gel (PAMG) that controllably and precisely shrinks and swells with water content. Aligned patterns of natural DNA molecules were prepared by evaporative self-assembly on a PMMA substrate, and were transferred to unsaturated polyester resin (UPR) to form a negative replica. The negative was used to pattern the linear structures onto the surface of water-swollen PAMG, and the pattern sizes on the PAMG stamp were customized by adjusting the water content of the PAMG. As a result, consistent reproduction of DNA patterns could be achieved with feature sizes that can be controlled over the range of 40%-200% of the original pattern dimensions. This methodology is novel and may pave a new avenue for manufacturing stamp-based functional nanostructures in a simple and cost-effective manner on a large scale.