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JOURNAL OF SURGICAL RESEARCH · 2009 · IF 1.875

Determination of Microcirculatory Changes and Angiogenesis in a Model of Frostbite Injury In Vivo

Ole Goertz,Stefan Baerreiter,Andrej Ring,Birger Jettkant,Tobias Hirsch,Adrien Daigeler,Hans U. Steinau,Stefan Langer

Background The breakdown of skin microcirculation and the leukocyte–endothelium interaction are assumed to play a key role in the pathophysiology of frostbite injuries. However, little is known as yet. The aim was to develop an in vivo frostbite model to monitor microcirculatory changes and angiogenesis after frostbite injury. Materials and Methods Deep partial thickness frostbite injuries were inflicted with a no-touch-technique to the ears of hairless mice ( n   =   9). To this end, a gas jet of nitrogen vapor (T   =   –195,8   ±   2.7°C) was delivered onto an area of 1.9   mm 2 for 1,5 s. Intravital fluorescent microscopy in combination with FITC-dextran and Rhodamin 6   G as fluorescent dyes was used to assess microcirculatory changes, leukocyte behavior, and angiogenesis during the 14 d of wound healing. Results The area of no perfusion decreased significantly over the observed period, and perfusion was almost completely restored due to angiogenesis by d 14 (day 1: 1.89 [mm 2 ]   ±   0.44SEM, d 14: 0.02   ±   0.01). No post-traumatic extension of the trauma could be observed. Edema formation increased significantly up to d 7. The number of adherent leukocytes showed a significant increase during the first 7 d. Functional vessel density showed a significant post-frostbite decrease to 60% of the baseline value. Conclusions This novel frostbite model provides a simple and nonetheless highly effective technique of creating locally limited reproducible frostbite injuries using a no touch technique. Tissue damage can be fully attributed to the thermal trauma, and the model allows repetitive intravital fluorescent microscopy of the microcirculation, leukocyte–endothelium interaction, and angiogenesis.

研究领域: 医学 · 生物学
✓ 已验证 DOI 高影响因子
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ACS Biomaterials Science & Engineering · 2025 · IF 5.5

Polydopamine Nanoparticle-Loaded Antifreezing and Photothermal Organohydrogel Based on Pullulan for Frostbite Therapy

Wenzhuang Cui,Ying Yue,Yujie Liu,Jun Wang,Zhizhou Yang,Yin Qiang,Chu Gong,Jun-Li Yang

Rapid rewarming is the standard and most common strategy for treating frostbite. Due to freezing susceptibility and lack of thermal effects, traditional therapeutic hydrogels are not suitable for being directly applied to frostbite therapy in cold conditions. Contrastively, antifreezing and photothermal hydrogels that are not apt to freeze and capable of rewarming frostbite wounds are deemed to hold great application potential in such therapy. Nevertheless, these hydrogels have rarely been researched. Herein, using glycerol as the cryoprotectant and polydopamine nanoparticles (PDA NPs) as the photothermal agent, a novel pullulan-based antifreezing and photothermal organohydrogel (CPG-PDA organohydrogel) was successfully developed to treat frostbite for the first time. The CPG-PDA organohydrogel formed through 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDC·HCl)-mediated esterification reactions was found to possess certain mechanical stability, shear-thinning behaviors (injectability), excellent antifreezing properties, superb in vitro and in vivo photothermal performances, and outstanding cytocompatibility and hemocompatibility. Most noticeably, the photothermal rewarming and coating therapy using the CPG-PDA organohydrogel was observed to significantly accelerate the frostbite healing of rats. The CPG-PDA organohydrogel was opined to be a promising platform for the direct treatment of frostbite in a cold environment and would open a new avenue for the design of therapeutic strategies for frostbite.

研究领域: 材料科学 · 生物医学工程 · 药剂学
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Design and Development of Fiber Patch to Prevent Reperfusion Injury and Provide Thermal Stimulation for Treating Severe Frostbite

Xilin Li,Junjiang Pan,Mingjie Liu,Enning Zhang,Yan Li,Yang He,Guang Yang,Shaobing Zhou

Frostbite is a prevalent form of acute cold injury that can cause extensive tissue damage, often requiring amputation. However, most clinical interventions face the challenge of preventing or mitigating reperfusion injury while restoring the blood supply. In this study, a fiber patch is developed with reperfusion injury prevention and thermal stimulation capabilities for frostbite treatment. Encapsulating itaconic acid (ITA) within the surface knots of the fabricated necklace-like polymer fibers optimizes its release kinetics, effectively inhibiting the generation of reactive oxygen species (ROS) through metabolic pathways. Localized thermal stimulation from the fiber matrix modulates cytokine secretion and promotes microcirculation remodeling in frostbitten tissues. In a study involving a third-degree frostbite model, the fiber patch demonstrates superior therapeutic efficacy in accelerating tissue repair, outperforming conventional pharmaceutical treatments. Hence, this study provides a portable, effective, and preventive solution for frostbite management.

研究领域: 生物医学工程 · 材料科学 · 急诊医学 · 热疗 · 药理学
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Regenerative Therapy · 2024 · IF 3.4

In situ forming Hydrogel with adding ZnO Nano-particle for effectively methicillin-resistant Staphylococcus aureus infected frostbite injury

Xun Xu,Jun Wang,Tian-Ci Sun,Qing Li,Ren-De Ning

Hydrogel has emerged as a promising wound dressing material, and in situ forming hydrogel has emerged as a promising wound dressing recently. But most in situ forming hydrogel are normally unstable. Herein, we report an in-situ forming hydrogel synthesized from poly(Nisopropylacrylamide166- co - n -butyl acrylate9)-poly(ethyleneglycol)-poly(N-isopropylacrylamide166- co - n -butyl acrylate9) copolymer (P(NIPAM166- co -nBA9)-PEG-P(NIPAM166-conBA9), denoted as PEP) and zinc oxide nano-particle(ZnO nano-particle) in response to skin temperature. This thermoresponsive hydrogel exhibits sol-gel reversibility at high temperatures, which is closed to the temperature of human skin. To investigate its healing effects, we used the Hydrogel dressing® in an SD rat model. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA) of this PEP-ZnO hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected frostbitten skin Injury. Materials and methods Thirty rats were randomly divided into two groups. The treatment group received hydrogel and transparent film dressing 30 min to 1 h post-burn, while the control group received only cotton dressing. The wound area was measured, and the wound closure rate was calculated on days 3, 7, and 14 post-surgery. Tissue samples were collected from each rat on these days and stored at −80 °C for histological analysis using H&E, Masson and immunohistochemical staining. This analysis assessed factors such as granulation tissue length, re-epithelialization, re-angiogenesis, collagen deposition, inflammatory cell infiltration, and collagen production. Clinical and histological assessments at 14 days showed more rapid healing in the hydrogel dressing group compared to the control group. Conclusion Our results indicate that the design of our hydrogel for cooling injury wounds effectively improves healing and mitigates the damage from low temperatures.

研究领域: 生物材料学 · 微生物学 · 医学工程 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Advanced Materials Interfaces · 2024 · IF 4.3

Preparation and Properties of Antifreeze Rewarming Hydrogel Dressings

Meng Yan,Xiaorong Dong,Jingjing Sun,Yijun Liu,Shengchao Yang,Xing Tian,Shuang Zheng,Lisha Yin,Yanan Fu,Dongmei Li,Lin Cui,Gang Li,Zhongpeng Qiu,Zhiyong Liu

The Hydrogel wound dressing with good rewarming property, anti-freezing property, and adhesion property has important practical significance in medical care for the first and second grade frostbite. The ears, hands, mouth, and nose of field workers on duty and training high cold region are prone to frostbite due to long-term exposure to in severe cold. Therefore, rapid rewarming of wound surface is the key to the treatment of frostbite. In this paper, antifreeze and rewarming are achieved by photothermal conversion materials and quaternary ammonium salts. Herein, the PAM/CS/MXene30/Betaine5/AgNPs200(PCM30B5A200) hydrogel based on chitosan (CS) and acrylamide (AM) is designed and fabricated by thermally initiated free radical polymerization. The dressing has excellent rewarming properties, anti-freezing properties, tensile properties, repeatable self-adhesion and antibacterial properties. In this system, hydrogels are mainly cross-linked by hydrogen bonds between CS and AM. Betaine is added to the material to make the hydrogel have good freeze-resistance and flexibility at −24 °C, and can be combined with AgNPs and MXene, to achieve a triple antibacterial. The PCM30B5A200 hydrogel reached the rewarming temperature of 40.5 °C at 9 min. PCM30B5A200 multifunctional hydrogels have good application value in the first and second grade frostbite wounds.

CAS / MDL: 107-43-7
研究领域: 材料科学 · 生物医学工程 · 伤口护理
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Topical frankincense treatment for frostbite based on microcirculation improvements

Zhao Zhang,Si-Yuan Ma,Xin Yin,Yu-Sang Li,He-Bin Tang

Ethnopharmacological relevance The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. Aim of the study To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. Materials and methods The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. Results FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and β-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. Conclusions FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.

CAS / MDL: 78-70-6
研究领域: 药理学 · 中医 · 伤口愈合 · 微循环
✓ 已验证 产品关联 DOI PubMed 高影响因子
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