Journal of Leather Science and Engineering最新文献

Amphiphilic block and random copolymers: aggregation and hydrophobic modification on metal-free tanned collagen fibers 两亲嵌段共聚物和无规共聚物：无金属鞣革胶原纤维上的聚集和疏水改性

Journal of Leather Science and Engineering

Pub Date : 2024-07-03 DOI: 10.1186/s42825-024-00163-9

Yudan Yi, Xinxin Fan, Qijun Li, Ya-nan Wang

Hydrophobicity enhancement of metal-free leather, which is crucial for improving its comprehensive performance, can be achieved by using amphiphilic copolymer retanning agents. However, the relationship between the sequential structure and the hydrophobic modification effect of amphiphilic copolymers remains unclear. Herein, an amphiphilic block copolymer was synthesized using stearyl methacrylate and 2-(dimethylamino)ethyl methacrylate via atom transfer radical polymerization, and the corresponding random copolymer with similar monomer compositions and molecular weights was prepared for comparison. The aggregation behavior of block and random copolymers was investigated. DLS and TEM results indicate that the block copolymer exhibits a larger aggregate size than the corresponding random copolymer. Molecular dynamics simulations suggest that the block copolymer aggregate exhibit a thicker hydrophilic shell and more concentrated distribution of cationic DMA block than the random copolymer aggregate. Subsequently, the block and random copolymers were used for the hydrophobic modification of metal-free tanned collagen fibers (CFs). The block copolymer shows superior binding capacity to CFs than the random one because of its larger size and more concentrated charge distribution. Hence, the block copolymer can form a dense and uniform hydrophobic film on the surface of collagen fibrils and endow CFs with higher hydrophobicity than the random one. This work provides theoretical guidance for modulating the hydrophobicity of CFs by tailoring the sequential structure of amphiphilic copolymers, which is expected to inspire the manufacturing of high-performance metal-free leather.

Graphical Abstract

使用两亲共聚物复鞣剂可以增强无金属皮革的疏水性，这对提高其综合性能至关重要。然而，两亲共聚物的序列结构与疏水改性效果之间的关系仍不清楚。本文利用甲基丙烯酸硬脂酯和甲基丙烯酸 2-（二甲基氨基）乙酯通过原子转移自由基聚合合成了一种两亲性嵌段共聚物，并制备了单体组成和分子量相似的相应无规共聚物进行比较。研究了嵌段共聚物和无规共聚物的聚集行为。DLS 和 TEM 结果表明，嵌段共聚物的聚集尺寸大于相应的无规共聚物。分子动力学模拟表明，与无规共聚物相比，嵌段共聚物聚集体的亲水外壳更厚，阳离子 DMA 嵌段分布更集中。随后，将嵌段共聚物和无规共聚物用于无金属鞣制胶原纤维（CF）的疏水改性。与无规共聚物相比，嵌段共聚物的尺寸更大，电荷分布更集中，因此与胶原纤维的结合能力更强。因此，嵌段共聚物能在胶原纤维表面形成致密、均匀的疏水膜，并赋予胶原纤维比无规共聚物更高的疏水性。这项工作为通过定制两亲共聚物的序列结构来调节 CF 的疏水性提供了理论指导，有望为高性能无金属皮革的制造带来启发。

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引用次数: 0

On-demand engineered double-network gelatin/silicate composited hydrogels with enhanced wet adhesion and stable release of bioactive ion for promoting wound healing 按需设计的明胶/硅酸盐双网复合水凝胶具有更强的湿粘附性和生物活性离子的稳定释放，可促进伤口愈合

Journal of Leather Science and Engineering

Pub Date : 2024-07-02 DOI: 10.1186/s42825-024-00161-x

Xiaomin Luo, Lufeng Ji, Fen Ao, Chen Yang, Jiang Chang, Changyu Yin, Huijun Ren, Ming Teng, Liuying Li, Xinhua Liu

Silicate bioceramics have demonstrated great potential in hydrogel dressings for wound healing due to their special origins of promoting endothelial cell angiogenesis and inhibiting apoptosis of cardiomyocyte. However, there are still some deficiencies, such as insufficient biological activity, instability of silicate ion release, and lower wet adhesion on wounds with tissue exudate, limiting their further clinical applications. Herein, inspired by mussels, a multifunctional double-network hydrogel (FS/PAM-Gel-PDA) wound dressing composited gelatin with silicate ceramic powder with satisfactory wet adhesion, stable release of bioactive ions, hemostasis, and the ability of promoting vascular regeneration was engineered through specifically grafting dopamine to gelatin and introducing ferrous silicate ceramic powder into the hydrogel. The comprehensive experimental results substantiate that the FS/PAM-Gel-PDA has wet-adhesion strength of up to 21.78 kPa, and remains stably adherent to porcine myocardial tissues intuitively after bending, twisting, soaking in water, and stretching. The test results of ion release behavior in vitro show that the oxidation and agglomeration of ferrous silicate ceramic powder can be effectively inhibited by using dopamine to form an antioxidant layer on the surface of ceramic powder, and thus, the stable release of Fe²⁺ and SiO₄⁴⁻ effective ions can be realized. The animal experiment exhibits that FS/PAM-Gel-PDA can achieve rapid hemostasis in the lethal liver defect model. Meanwhile, the FS/PAM-Gel-PDA reveals the remarkable ability to promote wound healing in a full-thickness skin injury model, which can obviously accelerate skin re-epithelialization. To sum up, the FS/PAM-Gel-PDA has excellent wet adhesion and stable release of active ions to accelerate angiogenesis, which shows great potential in promoting wound healing.

Graphical Abstract

硅酸盐生物陶瓷具有促进内皮细胞血管生成和抑制心肌细胞凋亡的特殊功能，因此在伤口愈合的水凝胶敷料中显示出巨大的潜力。然而，水凝胶敷料仍存在一些不足，如生物活性不足、硅酸盐离子释放不稳定、对有组织渗出的伤口湿粘附性较低等，限制了其进一步的临床应用。本文受贻贝的启发，通过将多巴胺特异性接枝到明胶中，并在水凝胶中引入硅酸亚铁陶瓷粉末，设计出了一种明胶与硅酸亚铁陶瓷粉末复合的多功能双网络水凝胶（FS/PAM-Gel-PDA）伤口敷料，该敷料具有满意的湿粘附性、生物活性离子的稳定释放、止血和促进血管再生的能力。综合实验结果证明，FS/PAM-Gel-PDA 的湿粘强度高达 21.78 kPa，在弯曲、扭转、浸水和拉伸后仍能直观地与猪心肌组织保持稳定粘附。体外离子释放行为测试结果表明，利用多巴胺在陶瓷粉体表面形成抗氧化层，可有效抑制硅酸亚铁陶瓷粉体的氧化和团聚，从而实现Fe2+和SiO44-有效离子的稳定释放。动物实验表明，FS/PAM-Gel-PDA 可在致死性肝缺损模型中实现快速止血。同时，FS/PAM-Gel-PDA 在全厚皮肤损伤模型中显示出显著的促进伤口愈合能力，可明显加速皮肤的再上皮化。综上所述，FS/PAM-凝胶-PDA具有良好的湿粘附性和稳定的活性离子释放，可加速血管生成，在促进伤口愈合方面具有很大的潜力。

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引用次数: 0

Development of mADM-collagen wound dressings for mimicking native skin architecture to enhance skin wound healing 开发 mADM-胶原蛋白伤口敷料，用于模拟原生皮肤结构，促进皮肤伤口愈合

Journal of Leather Science and Engineering

Pub Date : 2024-07-01 DOI: 10.1186/s42825-024-00159-5

Xiang Wang, Yujia Jiang, Xiaoqin Sun, Chongxia Yue, Zhengyong Li, Yao Wu

Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing.

Graphical Abstract

细胞外基质（ADM）能够保留天然细胞外基质结构，是最有前途的支架材料之一。通过高静水压（HHP）方法制备的微粉化细胞外基质（mADM）没有完整的细胞核，并保留了生长因子。并使用不同比例的 I 型胶原蛋白和重组人源化 III 型胶原蛋白开发了 mADM-胶原蛋白伤口敷料。mADM 胶原伤口敷料的多孔结构使其成为防止液体过度积聚的理想选择，而具有凝胶质地的胶原蛋白与 mADM 粉末结合形成糊状质地的伤口敷料，可保持伤口部位的湿度。此外，mADM-胶原蛋白伤口敷料的糊状质地易于重塑，以适应任何伤口形状和身体轮廓。此外，制成的 mADM-胶原伤口敷料在体外支持成纤维细胞的粘附和增殖，表现出良好的生物相容性。随后，我们利用小鼠全厚皮肤伤口模型来评估其对伤口愈合的影响。值得注意的是，mADM-75% Col-I 在整个伤口愈合过程中表现出卓越的效果，特别是它能促进血管新生、皮肤附属物生长和新皮肤再生。这种配方非常接近健康皮肤中的胶原蛋白比例，有利于伤口修复。这些结果表明，这种 mADM 胶原伤口敷料性能优越，可为伤口愈合提供最佳环境。

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引用次数: 0

Impact of tannery wastes on anaerobic co-digestion: enhancing biogas production and process efficiency 制革废料对厌氧协同消化的影响：提高沼气产量和工艺效率

Journal of Leather Science and Engineering

Pub Date : 2024-06-02 DOI: 10.1186/s42825-024-00162-w

Fetra J. Andriamanohiarisoamanana, Mohamed Farghali, Israa M. A. Mohamed, Gen Yoshida, Kazuya Shiota, Ikko Ihara

The study investigates the potential of anaerobic co-digestion (AcoD) as a sustainable solution for managing putrescible organic waste generated by leather processing. Three experiments were conducted to assess the impact of various tannery wastes, pretreatment methods, and waste combinations on methane production. Experiment 1 demonstrated that co-digesting tannery wastewater primary sludge (TWPS) and fleshings significantly increased methane yield compared to digesting TWPS alone, though the addition of chromium- and vegetable-tanned leather wastes decreased yield. Experiment 2 explored TWPS pretreatment methods and found that ultrasonic pretreatment increased soluble chemical oxygen demand (SCOD) but did not significantly improve methane yield, suggesting that pretreatment may not be necessary. Experiment 3 revealed that increasing the proportion of fleshings to TWPS resulted in higher methane yield, ranging from 226.52 mL/gVS with 6% fleshings to 395.71 mL/gVS and 538.34 mL/gVS with 12% and 20% of fleshings, respectively. Additionally, this increase in fleshings also led to a reduction in digester volume. These findings highlight the importance of AcoD in addressing both environmental and economic challenges in the leather industry.

Graphical Abstract

这项研究探讨了厌氧协同消化（AcoD）作为一种可持续的解决方案来管理皮革加工过程中产生的可腐烂有机废物的潜力。研究人员进行了三项实验，以评估各种制革废物、预处理方法和废物组合对甲烷产生的影响。实验 1 表明，与单独消化制革废水初级污泥（TWPS）相比，共同消化制革废水初级污泥（TWPS）和肉渣可显著提高甲烷产量，但添加铬和植鞣革废物会降低甲烷产量。实验 2 探讨了 TWPS 的预处理方法，发现超声波预处理增加了可溶性化学需氧量 (SCOD)，但并未显著提高甲烷产量，这表明预处理可能并非必要。实验 3 发现，增加 TWPS 中肉类的比例可提高甲烷产量，从肉类比例为 6% 时的 226.52 mL/gVS 到肉类比例为 12% 时的 395.71 mL/gVS 和 20% 时的 538.34 mL/gVS。此外，去肉量的增加也导致了消化器容积的减少。这些研究结果突显了 AcoD 在应对皮革业环境和经济挑战方面的重要性。

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引用次数: 0

Injectable dECM-enhanced hyaluronic microgels with spatiotemporal release of cartilage-specific molecules to improve osteoarthritic chondrocyte’s function 可注射的 dECM 增强型透明质酸微凝胶可按时空释放软骨特异性分子，改善骨关节炎软骨细胞的功能

Journal of Leather Science and Engineering

Pub Date : 2024-06-01 DOI: 10.1186/s42825-024-00158-6

Siyan Deng, Hongfu Cao, Yan Lu, Wenqing Shi, Manyu Chen, Xiaolin Cui, Jie Liang, Yujiang Fan, Qiguang Wang, Xingdong Zhang

The interior environment of articular cartilage in osteoarthritis (OA) presents substantial hurdles, leading to the malfunction of chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix. Despite this, most clinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression. This study aimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic (HE) microgels. The HE hydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerization techniques. These microgels provided a spatiotemporal cascade effect, facilitating the rapid release of growth factors and a slower release of ECM macromolecules and proteins. This process assisted in the recovery of OA chondrocytes’ function, promoting cell proliferation, matrix synthesis, and cartilage-specific gene expression in vitro. It also effectively aided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA, as demonstrated by radiological observation, gross appearance, histological/immunohistochemical staining, and analysis in an OA rat model in vivo. Collectively, the HE injectable microgels with spatiotemporal release of cartilage-specific molecules have shown promise as a potential candidate for a cell-free OA therapy approach.

Graphical Abstract

骨关节炎（OA）的关节软骨内部环境存在巨大障碍，导致软骨细胞功能失调和富含胶原蛋白 II 的透明软骨基质分解。尽管如此，大多数临床治疗方法只能暂时缓解 OA 带来的不适，却无法阻止 OA 的发展。本研究旨在通过开发可关节内注射的 dECM 增强透明质酸（HE）微凝胶来缓解 OA。利用微流体技术和光聚合技术，将透明质酸水凝胶设计和成型为大小一致的微凝胶。这些微凝胶产生了时空级联效应，促进了生长因子的快速释放以及 ECM 大分子和蛋白质的缓慢释放。这一过程有助于恢复 OA 软骨细胞的功能，促进细胞增殖、基质合成和体外软骨特异性基因表达。在 OA 大鼠模型中进行的放射学观察、大体外观、组织学/免疫组织化学染色和体内分析表明，它还能有效帮助修复富含胶原蛋白 II 的透明软骨，并显著减轻 OA 的严重程度。总之，具有软骨特异性分子时空释放功能的 HE 可注射微凝胶有望成为无细胞 OA 治疗方法的潜在候选材料。

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引用次数: 0

Injectable hyaluronate/collagen hydrogel with enhanced safety and efficacy for facial rejuvenation 可注射透明质酸/胶原蛋白水凝胶，提高面部年轻化的安全性和有效性

Journal of Leather Science and Engineering

Pub Date : 2024-06-01 DOI: 10.1186/s42825-024-00165-7

Lu Song, He Qiu, Zhiru Chen, Jing Wang, Yang Xu, Zhanhong Liu, Shuo Liu, Zhiyuan Wang, Xiangdong Zhu, Kai Zhang, Hai Lin, Xingdong Zhang

Collagen, known for its excellent biocompatibility and biological properties, has limited in vivo maintenance duration after implantation, while hyaluronic acid faces challenges such as various complications and insufficient support for cell proliferation. In this study, an injectable hyaluronic acid/collagen (HCol) hydrogel was developed to achieve enhanced cell-material interactions and accelerated skin regeneration. Physical and chemical characterizations demonstrated that the HCol hydrogel was injectable and stable after the implantation. In vitro cell culture results illustrated that the hydrogel promoted the proliferation of human dermal fibroblasts, extracellular matrix expression and angiogenesis. The subcutaneous implantation in rats showed the superior biocompatibility of HCol hydrogel and enhanced secretion and deposition of extracellular matrix, compared with commercial hyaluronic acid dermal filler. MRI analysis showed that the hydrogel stably remained in vivo for at least three months. The histological examination and SHG signals further demonstrated that the hydrogel modulated fibroblast phenotype and stimulated vascular ingrowth and collagen synthesis, without inducing significant inflammation, swelling or erythema in vivo.

Graphical Abstract

胶原蛋白以其出色的生物相容性和生物特性而著称，但植入后的体内维持时间有限，而透明质酸则面临各种并发症和细胞增殖支持不足等挑战。本研究开发了一种可注射的透明质酸/胶原蛋白（HCol）水凝胶，以增强细胞与材料的相互作用，加速皮肤再生。物理和化学特征表明，HCol 水凝胶可注射，植入后稳定。体外细胞培养结果表明，水凝胶能促进人类真皮成纤维细胞的增殖、细胞外基质的表达和血管生成。大鼠皮下植入试验表明，与商用透明质酸皮肤填充剂相比，HCol 水凝胶的生物相容性更好，细胞外基质的分泌和沉积也更强。核磁共振成像分析表明，水凝胶在体内可稳定存留至少三个月。组织学检查和 SHG 信号进一步表明，水凝胶调节了成纤维细胞的表型，刺激了血管生长和胶原蛋白合成，而不会在体内诱发明显的炎症、肿胀或红斑。

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引用次数: 0

Light-controlled crosslinked multifunctional "Band-Aids" as dual-stage wound dressing for dynamic wound closure 光控交联多功能 "创可贴 "作为动态闭合伤口的双层伤口敷料

Journal of Leather Science and Engineering

Pub Date : 2024-06-01 DOI: 10.1186/s42825-024-00167-5

Xinyue Zhang, Xue Zhan, Chen Hu, Zuqin Dong, Tao Luo, Haihang Li, Xiaoju Fan, Jie Liang, Yafang Chen, Yujiang Fan

The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites. Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balances material function, degradation, safety, and tissue growth. In this study, we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type III collagen (rhCol III-MA) and methacrylic anhydride-modified dopamine (DMA) (RMDM), which was synthesized through free radical polymerization and π-π stacking. Within this system, RMDM was formulated into two forms with identical compositions: hydrogel and sponge, tailored for application across various stages of wound repair. These materials displayed favorable hemocompatibility, biocompatibility, antioxidant properties, and angiogenic potential in vitro. Moreover, the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models. Notably, the sponge/gel (S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model, underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages. Therefore, this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing, which may have significant potential for biomedical applications.

Graphical Abstract

再生伤口愈合敷料的目标是加速皮肤组织再生，恢复伤口部位的正常生理功能。实现这一目标需要生物材料能够修复伤口愈合的不同阶段，同时兼顾材料功能、降解、安全性和组织生长。在这项研究中，我们介绍了一种新型双阶段伤口敷料系统，该系统由甲基丙烯酸酐改性重组人源化 III 型胶原蛋白（rhCol III-MA）和甲基丙烯酸酐改性多巴胺（DMA）（RMDM）组成，后者是通过自由基聚合和 π-π 堆积合成的。在这一系统中，RMDM 被配制成两种具有相同成分的形式：水凝胶和海绵，适用于不同阶段的伤口修复。这些材料在体外显示出良好的血液相容性、生物相容性、抗氧化性和血管生成潜力。此外，体内实验也表明，海绵能在小鼠断尾和肝脏切口模型中迅速止住伤口出血。值得注意的是，在大鼠全厚皮肤伤口模型中，海绵/凝胶（S/G）系统与单独的海绵和凝胶处理相比，可加速伤口愈合，这凸显了海绵和凝胶材料在伤口修复不同阶段的协同作用。因此，这项研究为设计可针对伤口愈合特定阶段的先进生物材料提供了宝贵的见解，这可能在生物医学应用方面具有巨大的潜力。

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引用次数: 0

Recent advances of collagen composite biomaterials for biomedical engineering: antibacterial functionalization and 3D-printed architecturalization 用于生物医学工程的胶原复合生物材料的最新进展：抗菌功能化和三维打印结构化

Journal of Leather Science and Engineering

Pub Date : 2024-05-22 DOI: 10.1186/s42825-024-00164-8

Lu Zheng, Natalya Tseomashko, Anastasiia Voronova, Alexander Vasil’kov, Xiaoqing Hu, Xiaoying Wang

Collagen possesses high biocompatibility with all tissue and cell types in the body, enabling the creation of multifunctional composite materials for medical applications. In biomedical engineering, naturally-sourced collagen is often combined with diverse organic and inorganic bioactive components to eliminate defects and disorders in fields including orthopedics, dermatology, and more. At the same time, medical-related infection issues and the precise treatment needs of patients require collagen composite biomaterials to have antibacterial properties and customized structures. This paper reviews the antibacterial functionalization of collagen composite biomaterials in recent years, including the combination with inorganic or organic antibacterial agents, which is beneficial for preventing and controlling biological contamination in medical applications. Then, the existing problems and future development directions for the architecturalization of collagen composite materials with 3D printing were discussed, providing guidance for personalized customization of multifunctional materials to meet the specific needs of patients in the future.

Graphical Abstract

胶原蛋白与人体内所有组织和细胞类型都具有很高的生物相容性，因此可以制造出用于医疗应用的多功能复合材料。在生物医学工程中，天然胶原蛋白通常与各种有机和无机生物活性成分相结合，以消除骨科、皮肤科等领域的缺陷和疾病。与此同时，医疗相关的感染问题和患者的精确治疗需求要求胶原蛋白复合生物材料具有抗菌性能和定制结构。本文回顾了近年来胶原蛋白复合生物材料的抗菌功能化，包括与无机或有机抗菌剂的结合，这有利于预防和控制医疗应用中的生物污染。然后，讨论了利用3D打印技术对胶原蛋白复合材料进行建筑化的现有问题和未来发展方向，为未来个性化定制多功能材料以满足患者的特殊需求提供指导。

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引用次数: 0

The potential of undenatured type II collagen against arthritis: a review 未变性 II 型胶原蛋白防治关节炎的潜力：综述

Journal of Leather Science and Engineering

Pub Date : 2024-05-02 DOI: 10.1186/s42825-024-00160-y

Yuhao Zhou, Yuer Zhang, Hongjie Dai, Yuhao Zhang, Yu Fu

The increasing global aging population has led to a continual rise in the prevalence of bone and joint diseases, posing challenges to both the quality of life for patients and healthcare resources. Type II collagen, a pivotal protein for sustaining joint function, has gained substantial attention in recent years. The oral administration of undenatured type II collagen (UC-II) has demonstrated noteworthy advancements in tackling bone and joint diseases. This article presents a comprehensive review of the structure and extraction methods of UC-II, discusses the relationship between UC-II and arthritis, and thoroughly examines its therapeutic role and potential mechanisms in the treatment process. In addition, future perspectives for clinical application of UC-II are discussed. It was found that the oral administration of UC-II, through induction of oral tolerance mechanisms, exhibits promise in alleviating joint inflammation and pain in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This method can significantly ameliorate joint inflammation and pain, with high patient acceptance and minimal side effects, demonstrating its potential as a well-tolerated treatment option for joint diseases.

Graphical Abstract

全球老龄化人口不断增加，导致骨关节疾病发病率持续上升，给患者的生活质量和医疗资源都带来了挑战。II 型胶原蛋白是维持关节功能的关键蛋白质，近年来受到广泛关注。口服未变性 II 型胶原蛋白（UC-II）在治疗骨关节疾病方面取得了显著进展。本文全面回顾了 UC-II 的结构和提取方法，讨论了 UC-II 与关节炎之间的关系，并深入研究了其在治疗过程中的治疗作用和潜在机制。此外，还讨论了 UC-II 临床应用的未来前景。研究发现，通过诱导口服耐受机制，口服 UC-II 有望缓解骨关节炎（OA）和类风湿性关节炎（RA）患者的关节炎症和疼痛。这种方法能明显改善关节炎症和疼痛，患者接受度高，副作用小，显示了其作为一种耐受性良好的关节疾病治疗方案的潜力。

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引用次数: 0

Therapeutic potential of gelatine methacrylate hydrogels loaded with macrophage-derived exosomes for accelerating angiogenesis and cutaneous wound healing 负载巨噬细胞外泌体的甲基丙烯酸明胶水凝胶在加速血管生成和皮肤伤口愈合方面的治疗潜力

Journal of Leather Science and Engineering

Pub Date : 2024-05-01 DOI: 10.1186/s42825-024-00156-8

Jiajun Liu, Fuying Chen, Luoqiang Tian, Jinjie Wu, Keting Liu, Qiwen Wan, Bo Yuan, Xiangdong Zhu, Xuening Chen, Xingdong Zhang

Extensive studies demonstrate that macrophage response plays an important role in regulating angiogenesis via a paracrine way, which is crucial for skin wound repair. This study isolated and characterized nanosized exosomes from differently polarized macrophages (MΦ), including M0 (naïve), M1 (pro-inflammatory), and M2 (anti-inflammatory) macrophages, and further assessed their impacts on angiogenesis and skin regeneration. Our results indicated that compared to M0 and M1 counterparts, M2 macrophage-derived exosomes (M2-Exos) exhibited a pronounced ability to promote angiogenic ability of of human umbilical vein endothelial cells (HUVECs) by enhancing expression of angiogenic genes and proteins, increasing cell migration, and improving tubulogenesis. Bioinformatics analyses suggested that the distinct angiogenic potentials of three MΦ-Exos might be attributed to the differentially expressed angiogenesis-related miRNAs and their target genes such as Stat3, Smad 2, and Smad4. Moreover, these isolated MΦ-Exos were integrated with gelatine methacrylate (GelMA) hydrogels to achieve the sustained delivery at murine full-thickness cutaneous wound sites. In vivo results showed that Gel/M2-Exos significantly augmented angiogenesis, accelerated re-epithelialization, promoted collagen maturity, thereby promoting wound healing. In contrary, Gel/M1-Exos showed the opposite effects. Our findings provided compelling evidence that the polarization status of macrophages significantly affected angiogenesis and wound healing via the miRNA cargos of their derived exosomes. Moreover, this study opens a new avenue for developing nano-scale, cell-free exosome-based therapies in treating cutaneous wounds.

Graphical abstract

大量研究表明，巨噬细胞反应通过旁分泌方式在调节血管生成方面发挥着重要作用，这对皮肤伤口修复至关重要。本研究从不同极化的巨噬细胞（MΦ）（包括M0（天真）、M1（促炎）和M2（抗炎）巨噬细胞）中分离并鉴定了纳米级外泌体，并进一步评估了它们对血管生成和皮肤再生的影响。我们的研究结果表明，与M0和M1对应物相比，M2巨噬细胞衍生的外泌体（M2-Exos）通过增强血管生成基因和蛋白的表达、增加细胞迁移和改善微管生成，表现出明显的促进人脐静脉内皮细胞（HUVECs）血管生成的能力。生物信息学分析表明，三种 MΦ-Exos 不同的血管生成潜能可能归因于血管生成相关 miRNA 及其靶基因（如 Stat3、Smad 2 和 Smad4）的不同表达。此外，这些分离出的 MΦ-Exos 与甲基丙烯酸明胶（GelMA）水凝胶结合，实现了在小鼠全厚皮肤伤口部位的持续递送。体内试验结果表明，Gel/M2-Exos能显著增强血管生成，加速再上皮化，促进胶原蛋白成熟，从而促进伤口愈合。相反，Gel/M1-Exos 则显示出相反的效果。我们的研究结果提供了令人信服的证据，表明巨噬细胞的极化状态会通过其衍生的外泌体所携带的 miRNA 显著影响血管生成和伤口愈合。此外，这项研究为开发基于纳米级无细胞外泌体的疗法治疗皮肤伤口开辟了一条新途径。

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