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Acta Biomaterialia · 2019 · IF 6.638

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

Xiao Yang,Wen Liu,Yifen Shi,Guanghui Xi,Mingshan Wang,Bin Liang,Yakai Feng,Xiangkui Ren,Changcan Shi

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.

研究领域: 生物材料学 · 医学工程 · 创伤修复
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Advanced Science · 2025 · IF 14.1

An Off-the-Shelf Artificial Blood Clot Hydrogel Neutralizing Multiple Proinflammatory Mediators for Pro-Regenerative Periodontitis Treatment

Yini Huangfu,Zhezhe Zhao,Xiang Liu,Jingrong Wang,Yufeng Zhang,Tingting Lan,Yonglan Wang,Chenxuan Wu,Ju Zhang,Pingsheng Huang,Chuangnian Zhang,Anjie Dong,Zujian Feng,Deling Kong,Weiwei Wang

Periodontitis is a destructive and chronic inflammatory disease initiated and sustained by multiple proinflammatory mediators. Current therapies mainly deal with bacteria elimination, but directly addressing the over-accumulated multiple inflammatory mediators in the periodontal microenvironment still remains a substantial challenge for regenerative periodontitis treatment. Herein, inspired by blood coagulation, an off-the-shelf artificial blood clot hydrogel encapsulated with platelet-rich plasma (PRP) is reported to mitigate the deteriorative inflammatory environment in periodontitis. The hydrogel (CCS-RSF@PRP) with a hierarchical fibers-interwoven network structure, in which the activated platelets are enriched, is structurally similar to the native blood clot. Functionally, in addition to the function of enriching and releasing growth factors, CCS-RSF@PRP can remarkably scavenge reactive oxygen species (ROS), neutralize endotoxin lipopolysaccharide (LPS), and proinflammatory cytokines (TNF-α, IFN-γ and IL-1β), inhibit M1 macrophage polarization and induce M2 macrophage polarization, thus blocking the chronic inflammatory feedback loop in the periodontitis. In rat periodontitis model, CCS-RSF@PRP hydrogel significantly expedits the repair of periodontium by normalizing the periodontal immune-environment. The work highlights the importance of local immunomodulation in the treatment of periodontitis, and the engineered PRP-derived hydrogel can mimic and expand the structure and function of native blood clot, holding great promise in treating chronic inflammatory diseases.

研究领域: 口腔医学 · 生物材料学 · 免疫学
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Brazilian Journal of Pharmaceutical Sciences · 2023 · IF 1.3

Study of the fibrinolytic activity of serrapeptase and its in vitro thrombolytic effects

Mei Jian feng,Cai Shao fen,Yi Yu,Wang Xu dong,Ying Guo qing

Serrapeptase, a proteolytic enzyme, has been used for the adjuvant treatment of many diseases. However, its fibrinolytic activity is still uncertain. Herein, the fibrinolytic activity of serrapeptase and its in vitro thrombolytic effects were investigated. The results showed that the fibrinolytic activity of serrapeptase was 1295 U/mg, and the specific activity was 3867 U/mg of protein when its proteolytic activity toward casein was 2800 U/mg. The optimum temperature and pH for serrapeptase activity were 37-40°C and 9.0, respectively. At 1 mmol/L, Zn2+, Mn2+ and Fe2+ could activate the fibrinolytic activity of serrapeptase, while K+, Cu2+, sodium dodecyl sulfate (SDS) and ethylene diamine tetraacetic acid (EDTA) inhibited it. In vitro tests showed that serrapeptase could completely prevent blood coagulation at 150 U/mL, and the percentage of blood clot lysis reached 96.6% at 37°C after 4 h at 300 U/mL. These results indicate that serrapeptase has excellent fibrinolytic activity, and can be used as a health food or candidate drug for the prevention or treatment of thrombotic diseases.

CAS / MDL: 9039-53-6 26097-80-3
研究领域: 生物化学 · 医学 · 药理学
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Advanced Healthcare Materials · 2024 ·Vol. 13 ·期 23 ·2400993 · IF 10

Janus Amphipathic Dressing With Liquid Self-Pumping and Blood-Clot Anti-Adhesion for Satisfactory Hemostasis

Qiao Yu,Wenjie Wang,Ningyue Deng,Baihai Su,Weifeng Zhao,Changsheng Zhao

Ideal hemostatic materials for the emergency rescue of war and traffic accident sufferers are essential to significantly control hemorrhage, reduce patient discomfort, and improve the survival ratio. However, most hemostats absorb blood quickly in contact with the wound; and then, adhere to blood clots, resulting in breaking scabs and tearing the wound when the materials are removed. Herein, an effective Janus amphipathic hemostatic dressing (Fiber@Gel/Ca 2+ /KL) with a fiber layer (polylactic acid/carboxymethyl chitosan) and a hydrogel layer (polyvinyl alcohol, carboxymethyl chitosan, Ca 2+ , and kaolin) is reported. Such a composite dressing unidirectionally drains the excessive serum from its hydrophobic side (fiber layer) to its hydrophilic side (hydrogel layer), so-called self-pumping, thereby further concentrating coagulated factors (including red blood cells and platelets). Further, Ca 2+ diffused from the hydrogel layer subsequently activates platelets and coagulation cascade. Besides, the Fiber@Gel/Ca 2+ /KL exhibits specific blood-clot anti-adhesion property on the fiber layer, making the dressing easily and safely peel off from the wound. It is believed that this novel hemostatic dressing with good hemostatic performance, easy clots removal, and excellent biocompatibility is expected to be used as a safe and efficient hemostatic dressing in clinical applications.

CAS / MDL: 471-34-1 1332-58-7
研究领域: 医学材料学 · 创伤急救 · 生物医学工程
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Small Structures · 2024 · IF 13.9

Nature Knows Best: Extracellular Matrix-Gelatin Hydrogel Masking Bioauthentic Bone Scaffold Locking Blood Clot to Induce M2 Macrophage-Mediated Bone Regeneration via Activating an Endocytosis-Macroautophagy-Inflammation Axis

Jieyun Xu,Xiaoran Yu,Hongcheng Chen,Junlong Xue,Zhuohong Gong,Zhengjie Shan,Shijie Chen,Yuanlong Guo,Xiaomeng Gao,Linjun Zhang,Yin Xiao,Feilong Deng,Zetao Chen

Individualized biological hydroxyapatite (BHA) scaffolds are essential for repairing critical craniomaxillofacial bone defects. Additive manufacturing relies on synthetic hydroxyapatite and biomimetic structures, making the resulting scaffolds inferior to natural bone. A subtractive manufacturing solution is proposed to cut natural bone blocks and then sinter them into BHA scaffolds. However, BHA scaffolds with fragile mechanical performance, fail to maintain scaffold integrity, due to microcracks generated by loss of organics from extracellular matrix (ECM). To preserve natural structure and enhance mechanical properties, ECM-gelatin hydrogel (ECM-Gel) is utilized as a micron-level coating to smooth surface microcracks like a facial mask. ECM-Gel shows potential in regulating blood clot fibrin network which may induce a favorable macrophage-mediated bone regeneration. Therefore, a gelatin hydrogel-masked BHA (G-BHA) scaffold system is developed using crosslinker genipin (2 and 8 mM). ECM-Gel formed a “hybrid layer”, smoothing the micron-level microcracks and enhancing mechanical properties of BHA; it activated platelets to lock blood clot with dense fibrin network, inducing M2 macrophage via a potential endocytosis-macroautophagy-inflammation axis for bone regeneration. In vivo experiments confirmed G-BHA scaffolds promoted ectopic and in situ bone regeneration. Therefore, ECM-gel-masking demonstrates great potential in developing individualized bioauthentic bone scaffolds with favorable blood clot and macrophage-mediated bone regeneration.

CAS / MDL: 9000-70-8
研究领域: 组织工程 · 生物材料 · 骨再生 · 巨噬细胞生物学 · 医疗器械 · 生物力学
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