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The Platelet-Rich Plasma research ecosystem: From mechanistic insights to precision treatment in knee osteoarthritis 富血小板血浆研究生态系统:从膝关节骨关节炎的机制洞察到精确治疗
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-11-04 DOI: 10.1016/j.reth.2025.10.017
Isabel Andia , Alain Silvestre , Cristina Del Amo , Florent Eymard , Hervé Bard
Platelet-rich plasma (PRP) is now one of the most widely used orthobiologics in musculoskeletal medicine, with knee osteoarthritis (KOA) as its main indication. PRP represents a spectrum of autologous preparations with differing cellular and protein content. In this narrative review, we frame current knowledge as a “research ecosystem” spanning mechanistic biology, product characterization, randomized controlled trials (RCTs), systematic reviews and meta-analyses, methodological evaluations, expert consensus, and precision medicine. We highlight the diverse biological roles of PRP components, including the immunomodulatory activity of platelets, the dual regenerative and inflammatory effects of leukocytes, and emerging neutrophil–macrophage crosstalk. Advances in classification systems and deep learning–based quality control are also discussed. Across RCTs, PRP generally outperforms corticosteroids and hyaluronic acid in early to moderate KOA, with benefits lasting several months to a year. Methodological evaluation adds nuance: fragility index analysis confirmed PRP's advantage but showed individual trials were only modestly robust, while spin in systematic reviews often overstated benefits, underscoring the need for more rigorous RCTs and transparent reporting. Leukocyte and platelet concentrations do not explain outcomes, highlighting the importance of patient-specific factors such as metabolic status, inflammation, and structural phenotype. Progress remains hampered by inconsistent reporting, lack of a standardized classification system, and inadequate stratification. We propose a roadmap linking product characterization, standardized reporting, precision patient selection, and objective outcome measures, aiming to shift PRP from a generic injection toward a tailored regenerative therapy.
富血小板血浆(PRP)是目前肌肉骨骼医学中应用最广泛的骨科产品之一,膝关节骨关节炎(KOA)是其主要适应症。PRP代表了具有不同细胞和蛋白质含量的自体制剂的光谱。在这篇叙述性综述中,我们将当前的知识构建为一个“研究生态系统”,涵盖机制生物学、产品表征、随机对照试验(rct)、系统综述和荟萃分析、方法学评估、专家共识和精准医学。我们强调了PRP成分的多种生物学作用,包括血小板的免疫调节活性,白细胞的双重再生和炎症作用,以及新出现的中性粒细胞-巨噬细胞串扰。还讨论了分类系统和基于深度学习的质量控制方面的进展。在所有随机对照试验中,PRP在早期至中度KOA中通常优于皮质类固醇和透明质酸,其益处持续数月至一年。方法学评估增加了细微差别:脆弱性指数分析证实了PRP的优势,但表明单个试验的可靠性并不高,而系统评价往往夸大了PRP的益处,强调了更严格的随机对照试验和透明报告的必要性。白细胞和血小板浓度不能解释结果,强调了患者特异性因素(如代谢状态、炎症和结构表型)的重要性。由于报告不一致、缺乏标准化分类系统和分层不充分,进展仍然受到阻碍。我们提出了一个路线图,将产品特性、标准化报告、精确患者选择和客观结果测量联系起来,旨在将PRP从通用注射转向量身定制的再生治疗。
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引用次数: 0
Microbiome-based profiles of airborne bacteria to support microbial risk assessment in cleanroom environments 基于微生物组的空气传播细菌概况,以支持洁净室环境中的微生物风险评估
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-11-01 DOI: 10.1016/j.reth.2025.10.019
Mitsuru Mizuno , Yusuke Ogata , Yuto Nishihara , Miwako Nishio , Hisako Katano , Ichiro Sekiya

Introduction

Maintaining aseptic conditions is essential for cell product processing, as sterilization cannot be applied to living cells. Conventional environmental monitoring relies on particle counts and culture-based colony-forming unit measurements. These indicators fail to capture much of the diversity and provenance of airborne microbes because many taxa are nonculturable or require growth conditions not supported by standard culture media. Therefore, comprehensive DNA-based microbiome analysis is critical for evaluating microbial risks that conventional methods may overlook; however, such studies remain limited in cleanroom settings. This study aimed to comprehensively visualize the structure of airborne microbial communities in cleanroom environments and clarify microbial risks that cannot be fully captured by particle counts or culture-based methods.

Methods

We collected airborne bacterial DNA from cleanrooms with environmental Grades B, C, and D using a high-volume air sampler. The DNA was extracted and analyzed via 16S rRNA gene amplicon sequencing targeting the V3–V4 regions. Bioinformatic analysis was performed using the QIIME2 pipeline, and microbial diversity was assessed using alpha and beta diversity indices. Abundant taxa were categorized based on their likely origin (environment- or skin-derived), and their distributions were examined in relation to facility management practices.

Results

Analysis revealed the consistent detection of skin-associated bacteria, such as Cutibacterium and Corynebacterium, and environmental bacteria, including Bacillus and Paracoccus, across all cleanroom grades. Alpha- and beta-diversities exhibited no significant differences among the grades. However, temporary and irregular increases in skin-derived bacteria indicated operator-related non-persistent contamination. This interpretation was supported by skewness and kurtosis analyses, which indicated occasional but noticeable shifts in microbial abundance, particularly in high-grade cleanroom environments.

Conclusions

This study demonstrates the limitations of conventional culture-based monitoring and underscores the value of DNA-based approaches for characterizing airborne microbial communities in cleanrooms. The detection of temporary increases in skin-associated bacteria indicates that operator-related contamination can occur even under stringent environmental conditions. These findings support the development of integrated monitoring strategies that can capture both the composition and temporal fluctuations of airborne microbiota to enhance microbial risk assessment.
保持无菌条件对于细胞产品加工是必不可少的,因为灭菌不能应用于活细胞。传统的环境监测依赖于颗粒计数和基于培养的菌落形成单位测量。这些指标不能反映空气中微生物的多样性和来源,因为许多分类群是不可培养的,或者需要标准培养基不支持的生长条件。因此,全面的基于dna的微生物组分析对于评估传统方法可能忽略的微生物风险至关重要;然而,这类研究仍然局限于洁净室环境。本研究旨在全面可视化洁净室环境中空气微生物群落的结构,并阐明微生物风险,这些风险无法通过颗粒计数或基于培养的方法完全捕获。方法采用大容量空气采样器采集环境等级为B、C、D的洁净室空气中细菌DNA。提取DNA,针对V3-V4区进行16S rRNA基因扩增子测序分析。采用QIIME2管道进行生物信息学分析,采用α和β多样性指数评估微生物多样性。根据其可能的来源(环境源或皮肤源)对丰富的分类群进行了分类,并对其分布进行了与设施管理实践的联系。结果分析显示,在所有洁净室级别中,皮肤相关细菌(如表皮杆菌和棒状杆菌)和环境细菌(包括芽孢杆菌和副球菌)的检测结果一致。α和β多样性在年级间无显著差异。然而,皮肤源性细菌的暂时和不规则增加表明操作员相关的非持久性污染。偏度和峰度分析支持了这一解释,表明微生物丰度偶尔发生但明显的变化,特别是在高级洁净室环境中。本研究表明了传统的基于培养的监测方法的局限性,并强调了基于dna的方法在洁净室空气微生物群落特征分析中的价值。皮肤相关细菌暂时增加的检测表明,即使在严格的环境条件下,与操作员相关的污染也可能发生。这些发现为制定综合监测策略提供了支持,这些策略可以捕捉空气中微生物群的组成和时间波动,以加强微生物风险评估。
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引用次数: 0
Blood derivatives as monotherapy and combination therapy: A promising strategy for wound healing 血液衍生物作为单一疗法和联合疗法:一种有希望的伤口愈合策略
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-11-01 DOI: 10.1016/j.reth.2025.10.018
Majid Zamani , Mohammad Masumzadeh , Mohammadreza Mohammadi Hosn , Fatemeh Pouladkhay
Wound healing is a highly orchestrated biological process, and any disruption or delay in its progression can result in the formation of chronic wounds. Such conditions impose a considerable clinical and socioeconomic burden on both patients and healthcare systems. Over the years, numerous therapeutic strategies have been investigated to promote tissue repair, with varying degrees of success. Among these, blood-derived products have emerged as a focal point of interest, owing to their regenerative potential and bioactive composition. Preparations including platelet-rich plasma, platelet-rich fibrin, platelet lysates, and autologous conditioned serum have demonstrated the capacity to enhance healing through the delivery of concentrated growth factors and cytokines. Each derivative possesses distinct advantages and limitations determined by its cellular content, biomolecular profile, and method of preparation. Most commonly presented in liquid or gel form, these products can be applied to diverse wound types and tailored to specific treatment protocols. Their use may be autologous or allogeneic, and they can be employed alone or in combination with other therapeutic modalities to achieve synergistic effects. This review provides a comprehensive overview of the characteristics, preparation techniques, biochemical composition, and clinical efficacy of various blood derivatives, underscoring their value either as standalone interventions or as part of multimodal regimens in advancing wound healing.
伤口愈合是一个高度协调的生物过程,任何破坏或延迟其进展可导致慢性伤口的形成。这种情况给患者和医疗保健系统带来了相当大的临床和社会经济负担。多年来,已经研究了许多促进组织修复的治疗策略,并取得了不同程度的成功。其中,由于其再生潜力和生物活性成分,血液来源产品已成为关注的焦点。包括富血小板血浆、富血小板纤维蛋白、血小板裂解物和自体条件血清在内的制剂已证明能够通过输送浓缩的生长因子和细胞因子来促进愈合。每种衍生物都有其独特的优点和局限性,这取决于其细胞含量、生物分子特征和制备方法。这些产品通常以液体或凝胶形式呈现,可适用于不同类型的伤口,并针对特定的治疗方案进行定制。它们的使用可以是自体的或同种异体的,它们可以单独使用或与其他治疗方式联合使用以达到协同作用。本文综述了各种血液衍生物的特点、制备技术、生化成分和临床疗效,强调了它们作为单独干预措施或作为促进伤口愈合的多模式方案的一部分的价值。
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引用次数: 0
Regenerative effects of PRP-impregnated collagen-gelatin sponge in a full-thickness skin defect model prp -胶原-明胶海绵在全层皮肤缺损模型中的再生效果
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-30 DOI: 10.1016/j.reth.2025.10.015
Hajime Matsumine, Hiroshi Fujimaki, Yuuki Hasegawa, Yosuke Niimi, Hiroyuki Sakurai

Introduction

Artificial dermis is an essential biomaterial for reconstructing full-thickness skin defects. Pelnac G Plus® is a collagen-gelatin sponge (CGS) that can be impregnated with basic fibroblast growth factor (bFGF), offering sustained release and proven clinical efficacy. However, the off-label use of bFGF by impregnation remains restricted under current pharmaceutical regulations in Japan. In this study, we evaluated the wound healing potential of autologous platelet-rich plasma (PRP) as an alternative bioactive substance when impregnated into CGS.

Methods

Full-thickness skin defect models were created in nude rats and treated with artificial dermis alone (CGS group), artificial dermis + PRP (CGS + PRP group), or artificial dermis + bFGF (CGS + FGF group). Wounds were evaluated on postoperative day 14.

Results

On postoperative day 14, the CGS + PRP group exhibited significantly greater collagen thickness and vascular density than the CGS group. Furthermore, the CGS + PRP group showed a smaller wound area than the CGS + FGF group (20.9 ± 14.3 mm2 vs. 51.5 ± 18.0 mm2, p < 0.001). The CGS + PRP group also demonstrated higher α-SMA expression compared to the CGS + FGF group (36.6 % ± 4.3 % vs. 23.9 % ± 8.1 %, p < 0.001), and immunohistochemical analysis revealed higher expression of VEGF and α-SMA, suggesting enhanced angiogenesis and fibroblast activity. PRP preserved the expression of TGF-β1 and α-SMA, supporting balanced tissue regeneration.

Conclusions

Our findings demonstrate that bFGF and PRP exert distinct effects on wound healing in a secondary-intention model. bFGF effectively promoted dermis-like granulation tissue regeneration without accelerating contraction, supporting its use in anatomical sites where scar contracture must be avoided. In contrast, PRP enhanced wound contraction and ulcer area reduction, suggesting clinical utility in non-healing ulcers where delayed secondary healing is a major concern.
人工真皮层是修复全层皮肤缺损的重要生物材料。Pelnac G Plus®是一种胶原-明胶海绵(CGS),可浸透碱性成纤维细胞生长因子(bFGF),具有持续释放和临床疗效。然而,根据日本现行的制药法规,bFGF的超说明书使用仍然受到限制。在这项研究中,我们评估了自体富血小板血浆(PRP)作为一种替代生物活性物质浸染到CGS中时的伤口愈合潜力。方法建立裸鼠全层皮肤缺损模型,分别给予人工真皮层(CGS组)、人工真皮层+ PRP (CGS + PRP组)、人工真皮层+ bFGF (CGS + FGF组)治疗。术后第14天评估伤口。结果术后第14天,CGS + PRP组胶原厚度和血管密度明显高于CGS组。此外,CGS + PRP组的创面面积小于CGS + FGF组(20.9±14.3 mm2比51.5±18.0 mm2, p < 0.001)。与CGS + FGF组相比,CGS + PRP组α-SMA的表达也更高(36.6%±4.3%比23.9%±8.1%,p < 0.001),免疫组织化学分析显示VEGF和α-SMA的表达更高,表明血管生成和成纤维细胞活性增强。PRP维持TGF-β1和α-SMA的表达,支持平衡组织再生。结论在二次意向模型中,bFGF和PRP对伤口愈合有明显的促进作用。bFGF有效促进真皮样肉芽组织再生而不加速收缩,支持其用于必须避免瘢痕挛缩的解剖部位。相比之下,PRP增强了伤口收缩和溃疡面积的减少,表明在延迟二次愈合是主要问题的未愈合溃疡的临床应用。
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引用次数: 0
Magnesium-based alloys for bone regeneration and beyond: A review of advances and therapeutic prospects 镁基合金骨再生及其应用:进展及治疗前景综述
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-29 DOI: 10.1016/j.reth.2025.10.010
Lu-Hang Xu , Li-Tian Ye , Jia-Yu Wang , Xuan Qiu

Background

Magnesium (Mg)-based alloys have gained significant attention as next-generation biodegradable biomaterials due to their bone-mimetic mechanical properties (elastic modulus: 35–45 GPa), biocompatibility, and ability to degrade in vivo without toxic byproducts.

Objective

This review systematically evaluates recent advances in Mg-based alloys for biomedical applications, focusing on orthopedic implants, cardiovascular stents, and drug delivery systems, while identifying current challenges and future research directions.

Methods

We conducted a comprehensive literature analysis of peer-reviewed studies (2019–2024) examining Mg alloy development, surface modification techniques, in vitro/in vivo performance, and clinical trial outcomes.

Results

Key findings include: (1) Alloying innovations, particularly with rare-earth elements (e.g., in WE43) and nutrient elements (Zn, Ca), have yielded alloys with bone-mimetic mechanical properties (elastic modulus: 35–45 GPa; compressive yield strength: 150–250 MPa) and decelerated degradation rates via grain refinement and secondary phase formation; (2) Surface-modified Mg stents show improved endothelialization with 30–50 % reduced restenosis rates (3) Structurally engineered Mg-based scaffolds (e.g., via additive manufacturing); enable topological control over degradation through tailored porosity; (4) Drug-eluting Mg carriers achieve sustained release kinetics, leveraging degradation to simultaneously promote tissue regeneration and deliver therapeutics. However, rapid degradation (0.2–0.5 mm/year in physiological conditions) and hydrogen gas evolution remain critical challenges.

Conclusion

Mg-based alloys show transformative potential for temporary medical implants. Future research should focus on: (1) advanced alloy design with rare-earth elements, (2) smart coating technologies, and (3) standardized long-term biocompatibility assessments to facilitate clinical translation.
镁基合金作为下一代可生物降解的生物材料,由于其具有模拟骨的力学性能(弹性模量:35 - 45gpa)、生物相容性以及在体内降解无毒性副产物的能力而受到广泛关注。目的系统评价了近年来mg基合金在生物医学领域的应用进展,重点介绍了骨科植入物、心血管支架和药物输送系统,同时指出了当前面临的挑战和未来的研究方向。方法对同行评议的研究(2019-2024)进行综合文献分析,考察镁合金的发展、表面改性技术、体外/体内性能和临床试验结果。主要发现包括:(1)合金的创新,特别是稀土元素(如WE43)和营养元素(Zn, Ca),产生了具有骨模拟力学性能的合金(弹性模量:35-45 GPa,抗压屈服强度:150-250 MPa),并通过晶粒细化和二次相形成减慢了降解速率;(2)表面修饰的镁支架可以改善内皮化,减少30 - 50%的再狭窄率(3)结构工程的镁基支架(例如,通过增材制造);通过定制孔隙度实现对降解的拓扑控制;(4)药物洗脱Mg载体实现了缓释动力学,利用降解同时促进组织再生和提供治疗。然而,快速降解(生理条件下0.2-0.5 mm/年)和氢气释放仍然是关键的挑战。结论镁基合金在医用临时植入物方面具有转化潜力。未来的研究应集中在:(1)采用稀土元素的先进合金设计,(2)智能涂层技术,(3)标准化的长期生物相容性评估,以促进临床转化。
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引用次数: 0
Objective evaluation of platelet-rich plasma mesotherapy on facial skin quality: An interim split-face analysis using an advanced imaging system 目的评价富血小板等离子体治疗对面部皮肤质量的影响:一项使用先进成像系统的中期面部分裂分析
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-23 DOI: 10.1016/j.reth.2025.10.008
Masashi Umeda, Takahiko Tamura, Kohki Okumura, Reiko Kiuchi, Hiroo Teranishi

Introduction

Autologous platelet-rich plasma (PRP), which is rich in growth factors, is widely used in aesthetic medicine to improve facial skin quality. However, its efficacy has been largely supported by subjective evaluations and case reports; objective and quantitative evidence remains limited. This study aimed to objectively and quantitatively evaluate the effects of PRP mesotherapy on facial skin quality, using a validated image analysis system.

Methods

Nine healthy adults (six females and three males; median age, 34 years) employed at the Tokyo Chuo Beauty Clinic were enrolled in this study. A split-face design was used, with PRP injected into the left hemiface and saline injected into the right hemiface under identical conditions (5 mL each). Facial images were obtained at baseline, two weeks, and one month using the NeoVoir system, which automatically identifies ten facial regions and extracts multiple quantitative skin parameters. The percentage change from baseline was compared between the sides.

Results

The primary endpoint, the gloss area at one month, showed a significantly greater increase on the PRP-treated side than on the saline-treated side (median difference, 16.3 %; p = 0.0039). At two weeks, the gloss also improved more on the PRP side, although the difference was not significant after false discovery rate (FDR) correction. Pore scores showed a greater reduction on the PRP side at one month (median difference, −17.6 %; p = 0.0039), but this result did not remain statistically significant after FDR adjustment (q = 0.0663). No significant differences were observed in wrinkle area, melanin content, or pigmentation indices. No serious adverse events occurred; only transient, mild local reactions such as redness and swelling were noted on both sides.

Conclusion

This study provides novel objective evidence that PRP mesotherapy significantly improves facial gloss, a key feature of healthy young skin. An exploratory trend toward pore reduction was also observed, although mechanistic interpretations remain hypothesized owing to the absence of biophysical and structural measurements. Moving beyond subjective assessments, these findings support the potential of PRP for enhancing facial brightness, smoothness, and overall skin quality. Further studies with larger cohorts, extended follow-ups, and multimodal evaluations are warranted to validate and expand upon these preliminary results.
自体富血小板血浆(PRP)富含生长因子,在美容医学中被广泛应用于改善面部皮肤质量。然而,其有效性在很大程度上得到了主观评价和病例报告的支持;客观和定量的证据仍然有限。本研究旨在使用一种经过验证的图像分析系统,客观定量地评估PRP化疗对面部皮肤质量的影响。方法在东京中央美容诊所工作的9名健康成年人(6名女性,3名男性,中位年龄34岁)加入本研究。采用裂面设计,在相同条件下左半边脸注射PRP,右半脸注射生理盐水(各5ml)。使用NeoVoir系统在基线、两周和一个月获得面部图像,该系统自动识别10个面部区域并提取多个定量皮肤参数。比较双方从基线的百分比变化。结果主要终点(1个月时的光泽面积)显示,prp治疗组比盐水治疗组明显增加(中位数差异为16.3%;p = 0.0039)。两周后,PRP方面的光泽度也得到了更多的改善,尽管在错误发现率(FDR)校正后差异并不显著。一个月后,PRP侧的孔隙评分下降幅度更大(中位数差值为- 17.6%;p = 0.0039),但在FDR调整后,这一结果没有统计学意义(q = 0.0663)。在皱纹面积、黑色素含量或色素沉着指数方面没有观察到显著差异。未发生严重不良事件;只有短暂的,轻微的局部反应,如两侧红肿。结论:本研究提供了新的客观证据,证明PRP疗法可显著改善面部光泽,这是健康年轻皮肤的关键特征。尽管由于缺乏生物物理和结构测量,机制解释仍然是假设的,但也观察到孔隙减少的探索性趋势。超越主观评估,这些发现支持PRP在提高面部亮度、平滑度和整体皮肤质量方面的潜力。进一步的研究需要更大的队列、更长的随访和多模式评估来验证和扩展这些初步结果。
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引用次数: 0
Sulfated hyaluronic acid for wound repair: Mechanisms, materials, and translational challenges 硫酸透明质酸用于伤口修复:机制、材料和转化挑战
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-18 DOI: 10.1016/j.reth.2025.10.006
Min Lin , Danni Zhou , Kaixuan Chen , Hankang Jiang , Wenjie Chen , Jing Wu , Guizhi Zhu , Kailei Xu , Peng Wei
Sulfated hyaluronic acid (sHA) is emerging as a promising biomaterial for advanced wound dressings because it combines the intrinsic biocompatibility and extracellular matrix (ECM)-like hydration of hyaluronic acid (HA) with added chemical functionality that enhances stability and bioactivity. Chronic wounds, particularly diabetic ulcer, —remain a major clinical challenge due to persistent inflammation, protease/reactive oxygen species (ROS)-rich microenvironments, impaired angiogenesis, and poor growth-factor retention; native HA is limited by rapid enzymatic degradation, low protein affinity, and potentially pro-inflammatory low-molecular fragments, motivating strategies to introduce sulfate groups onto HA to tune its interactions with cells and proteins. In this review, we performed a comprehensive literature review of the biological functions and applications of sHA in wound healing. Key results demonstrate that sHA significantly enhances anti-inflammatory responses, promotes sustained release of cationic therapeutics, improves angiogenesis, and reduces fibrosis. Furthermore, sHA-functionalized hydrogels accelerate diabetic wound healing by modulating macrophage polarization, enhancing re-epithelialization, and supporting vascularization. In further, we also offered a practical roadmap for researchers and clinicians to rationally design next-generation sHA-based dressings with improved reproducibility, controlled release, and safety.
硫酸透明质酸(sHA)是一种很有前途的生物材料,用于高级伤口敷料,因为它结合了透明质酸(HA)固有的生物相容性和细胞外基质(ECM)样水合作用,并增加了化学功能,增强了稳定性和生物活性。慢性伤口,特别是糖尿病性溃疡,由于持续的炎症、蛋白酶/活性氧(ROS)丰富的微环境、血管生成受损和生长因子保留不良,仍然是一个主要的临床挑战;天然透明质酸受酶促降解速度快、蛋白质亲和力低和潜在的促炎低分子片段的限制,促使将硫酸盐基团引入透明质酸以调节其与细胞和蛋白质的相互作用。在这篇综述中,我们对sHA的生物学功能和在伤口愈合中的应用进行了全面的文献综述。关键结果表明,sHA显著增强抗炎反应,促进阳离子疗法的持续释放,促进血管生成,减少纤维化。此外,sha功能化的水凝胶通过调节巨噬细胞极化、增强再上皮化和支持血管化来加速糖尿病伤口愈合。此外,我们还为研究人员和临床医生提供了一个实用的路线图,以合理设计下一代基于sha的敷料,提高可重复性,控释性和安全性。
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引用次数: 0
Sevoflurane suppresses LPS-induced microglia injury by regulating USP11-mediated UHRF1 deubiquitination 七氟醚通过调节usp11介导的UHRF1去泛素化抑制lps诱导的小胶质细胞损伤
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-17 DOI: 10.1016/j.reth.2025.09.004
Dongzhi Liu, Chengliang Sun, Xiuli Zhang, Shunheng Gao

Background

Spinal cord injury (SCI) is a devastating neurological and pathological condition that leads to severe motor, sensory, and autonomic dysfunctions. The neuroprotective effect of Sevoflurane (Sevo) in the rat model of SCI has been reported. However, the mechanism of Sevo is still elusive.

Methods

24 rats were divided into four groups: sham group, sham + Sevo group, SCI group, and SCI + Sevo group. On days 0, 14, 28, and 42 post-SCI, functional recovery was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE staining. Western blotting, ELISA, and corresponding kits were used to detect the effects of Sevo on apoptosis, inflammatory factors, and oxidative stress. Human microglia HMC3 were induced by lipopolysaccharide (LPS) to mimic the in vitro environment of SCI. Ubiquitin-specific peptidase 11 (USP11) and ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), B-cell lymphoma-2 (BCL-2), and Bcl-2 related X protein (BAX) protein levels were determined using Western blot. Cell apoptosis, Interleukin-1β (IL-1β), and IL-6 levels were assessed using flow cytometry and ELISA. malondialdehyde (MDA), glutathione (GSH), and Reactive oxygen species (ROS) products were examined using special assay kits. After Ubibrowser prediction, GO enrichment, and protein-protein interaction (PPI) networks, the interaction between USP11 and UHRF1 was verified using Co-immunoprecipitation (CoIP) assay.

Results

Sevo treatment improved spinal cord functional recovery in rats, as evidenced by enhanced BBB locomotor rating scale and neuron death in vivo. Meanwhile, Sevo also reduced inflammation and oxidative damage in rats following SCI. Sevo exposure decreased USP11 and UHRF1 expression in LPS-treated HMC3 cells. Sevo repressed LPS-triggered HMC3 cell apoptosis, inflammatory response, and oxidative stress promotion by regulating USP11. At the molecular level, USP11 interacted with UHRF1 and maintained its stabilization by removing ubiquitin.

Conclusion

Sevo could protect LPS-induced HMC3 cell apoptosis, inflammation, and oxidative stress by regulating the USP11/UHRF1 axis, which might provide a novel therapeutic mechanism for Sevo in SCI.
脊髓损伤(SCI)是一种毁灭性的神经和病理状况,可导致严重的运动、感觉和自主神经功能障碍。报道了七氟醚(Sevo)在脊髓损伤大鼠模型中的神经保护作用。然而,Sevo的机制仍然是难以捉摸的。方法将24只大鼠分为4组:sham组、sham + Sevo组、SCI组、SCI + Sevo组。在脊髓损伤后第0、14、28和42天,采用血脑屏障试验评估功能恢复情况。HE染色观察脊髓组织学改变。采用Western blotting、ELISA及相应试剂盒检测Sevo对细胞凋亡、炎症因子和氧化应激的影响。采用脂多糖(LPS)诱导人小胶质细胞HMC3模拟体外脊髓损伤环境。Western blot检测泛素特异性肽酶11 (USP11)和泛素样蛋白,含PHD和环指结构域1 (UHRF1)、b细胞淋巴瘤-2 (BCL-2)和BCL-2相关X蛋白(BAX)蛋白水平。采用流式细胞术和ELISA检测细胞凋亡、白细胞介素-1β (IL-1β)和IL-6水平。丙二醛(MDA)、谷胱甘肽(GSH)和活性氧(ROS)产物采用特殊检测试剂盒检测。在Ubibrowser预测、氧化石墨烯富集和蛋白蛋白相互作用(PPI)网络之后,USP11和UHRF1之间的相互作用通过共免疫沉淀(CoIP)试验得到验证。结果svo治疗可改善大鼠脊髓功能恢复,血脑屏障运动评分和神经元死亡均有明显提高。同时,Sevo还能减轻大鼠脊髓损伤后的炎症和氧化损伤。在lps处理的HMC3细胞中,连续暴露降低了USP11和UHRF1的表达。通过调节USP11, Sevo抑制lps引发的HMC3细胞凋亡、炎症反应和氧化应激促进。在分子水平上,USP11与UHRF1相互作用,并通过去除泛素维持其稳定性。结论Sevo通过调控USP11/UHRF1轴对lps诱导的HMC3细胞凋亡、炎症和氧化应激具有保护作用,这可能为Sevo治疗脊髓损伤提供了一种新的机制。
{"title":"Sevoflurane suppresses LPS-induced microglia injury by regulating USP11-mediated UHRF1 deubiquitination","authors":"Dongzhi Liu,&nbsp;Chengliang Sun,&nbsp;Xiuli Zhang,&nbsp;Shunheng Gao","doi":"10.1016/j.reth.2025.09.004","DOIUrl":"10.1016/j.reth.2025.09.004","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) is a devastating neurological and pathological condition that leads to severe motor, sensory, and autonomic dysfunctions. The neuroprotective effect of Sevoflurane (Sevo) in the rat model of SCI has been reported. However, the mechanism of Sevo is still elusive.</div></div><div><h3>Methods</h3><div>24 rats were divided into four groups: sham group, sham + Sevo group, SCI group, and SCI + Sevo group. On days 0, 14, 28, and 42 post-SCI, functional recovery was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE staining. Western blotting, ELISA, and corresponding kits were used to detect the effects of Sevo on apoptosis, inflammatory factors, and oxidative stress. Human microglia HMC3 were induced by lipopolysaccharide (LPS) to mimic the <em>in vitro</em> environment of SCI. Ubiquitin-specific peptidase 11 (USP11) and ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), B-cell lymphoma-2 (BCL-2), and Bcl-2 related X protein (BAX) protein levels were determined using Western blot. Cell apoptosis, Interleukin-1β (IL-1β), and IL-6 levels were assessed using flow cytometry and ELISA. malondialdehyde (MDA), glutathione (GSH), and Reactive oxygen species (ROS) products were examined using special assay kits. After Ubibrowser prediction, GO enrichment, and protein-protein interaction (PPI) networks, the interaction between USP11 and UHRF1 was verified using Co-immunoprecipitation (CoIP) assay.</div></div><div><h3>Results</h3><div>Sevo treatment improved spinal cord functional recovery in rats, as evidenced by enhanced BBB locomotor rating scale and neuron death <em>in vivo.</em> Meanwhile, Sevo also reduced inflammation and oxidative damage in rats following SCI. Sevo exposure decreased USP11 and UHRF1 expression in LPS-treated HMC3 cells. Sevo repressed LPS-triggered HMC3 cell apoptosis, inflammatory response, and oxidative stress promotion by regulating USP11. At the molecular level, USP11 interacted with UHRF1 and maintained its stabilization by removing ubiquitin.</div></div><div><h3>Conclusion</h3><div>Sevo could protect LPS-induced HMC3 cell apoptosis, inflammation, and oxidative stress by regulating the USP11/UHRF1 axis, which might provide a novel therapeutic mechanism for Sevo in SCI.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 946-955"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting ER stress-mediated apoptosis by MSC-derived exosomes: A novel therapeutic strategy against pulmonary fibrosis 骨髓间质干细胞衍生外泌体靶向内质网应激介导的细胞凋亡:一种治疗肺纤维化的新策略
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-17 DOI: 10.1016/j.reth.2025.10.004
Ruixi Luo, Yaqiong Wei, La Wang, Peng Chen, Didong Lou, Weiyi Tian

Introduction

Idiopathic pulmonary fibrosis (IPF) is marked by a gradual decline in pulmonary function over time and is associated with a grim prognosis. In the pathogenesis of IPF, persistent endoplasmic reticulum (ER) stress plays a significant role in promoting fibrosis through pathways involving apoptosis. Mesenchymal stem cell-derived exosomes (MSC-Ex) have shown promise in mitigating pulmonary fibrosis by inhibiting apoptosis. Nonetheless, the precise mechanisms underlying this effect remain unclear. In our previous findings, we demonstrated that MSCs alleviate pulmonary fibrosis by regulating ER stress. Building upon this, we sought to investigate whether MSC-Ex could mitigate alveolar epithelial cell apoptosis through the ER stress pathway. We posited that targeting ER stress could represent a crucial mechanism by which MSC-Ex alleviate apoptosis in IPF models.

Methods and results

In this study, bleomycin (BLM) induced apoptosis in A549 cells, and MSC-Ex treatment reduced apoptotic cells and the Bax/Bcl-2 ratio. ER stress is involved in BLM-induced apoptosis in A549 cells, and MSC-Ex reduced ER stress-related protein (Bip and CHOP) expression and reversed the morphological changes of the ER in A549 cells. Moreover, blockade of ER stress with ER stress inhibitor TUDCA contributed to the amelioration of apoptosis in A549 cells, indicating that MSC-Ex reduced BLM-induced apoptosis at least partly by modulating ER stress. In vivo, MSC-Ex injection decreased BLM-induced pulmonary fibrosis in mice, as well as ER stress and apoptosis in the lung tissues.

Conclusions

In conclusion, ER stress induced apoptosis in BLM-treated A549 cells, and MSC-Ex treatment mitigated apoptosis via inhibiting ER stress. This study provides a novel mechanism for MSC-Ex-mediated protection on apoptosis in an IPF model and suggests that MSC-Ex could be a promising therapeutic strategy for IPF.
特发性肺纤维化(IPF)的特点是随着时间的推移肺功能逐渐下降,预后不佳。在IPF的发病机制中,持续内质网(ER)应激通过涉及细胞凋亡的途径在促进纤维化中起重要作用。间充质干细胞来源的外泌体(MSC-Ex)已显示出通过抑制细胞凋亡来减轻肺纤维化的前景。尽管如此,这种效应背后的确切机制仍不清楚。在我们之前的研究中,我们证明了间充质干细胞通过调节内质网应激来减轻肺纤维化。在此基础上,我们试图研究MSC-Ex是否可以通过内质网应激途径减轻肺泡上皮细胞凋亡。我们假设靶向内质网应激可能是MSC-Ex减轻IPF模型中细胞凋亡的关键机制。方法和结果在本研究中,博来霉素(BLM)诱导A549细胞凋亡,MSC-Ex处理可降低凋亡细胞数和Bax/Bcl-2比值。内质网应激参与了blm诱导的A549细胞凋亡,MSC-Ex可降低内质网应激相关蛋白(Bip和CHOP)的表达,逆转A549细胞内质网形态学变化。此外,内质网应激抑制剂TUDCA阻断内质网应激有助于改善A549细胞的凋亡,这表明MSC-Ex至少在一定程度上通过调节内质网应激来减少blm诱导的细胞凋亡。在体内,MSC-Ex注射液可减轻blm诱导的小鼠肺纤维化,减少肺组织内质网应激和细胞凋亡。结论内质网应激可诱导blm处理的A549细胞凋亡,而MSC-Ex可通过抑制内质网应激减轻细胞凋亡。本研究提供了一种新的MSC-Ex在IPF模型中介导细胞凋亡保护的机制,并表明MSC-Ex可能是一种有前景的IPF治疗策略。
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引用次数: 0
Multimodal mechanisms of platelet-rich plasma in bone defect repair: Angiogenesis, inflammation modulation, and metabolic regulation 富血小板血浆在骨缺损修复中的多模式机制:血管生成、炎症调节和代谢调节
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-10-15 DOI: 10.1016/j.reth.2025.09.007
Junjie Chen , Bo Liu , Jiayang He , Yuhao Wei , Yuhan He , Hang Zhou , Zhiqiang Zhang , Yiwen Weng , Ming Cheng
Bone defect is the loss of bone tissue due to trauma, fracture, infection, etc. This loss may lead to non-union of fracture, bone defect or bone deficiency, which seriously affects the patient's quality of life and even leads to dysfunction and disability. Although surgical repair is a common treatment modality, the surgical procedure is complicated, with a long postoperative recovery period and certain surgical risks, such as infection and bleeding. Platelet-rich plasma (PRP), as a novel therapeutic approach, has demonstrated remarkable potential in bone defect repair. PRP is rich in growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), etc., and can have a beneficial effect on bone defect repair through various mechanisms, such as the release of growth factors, the promotion of angiogenesis, the inhibition of inflammatory response, and the recruitment of activated cells and other mechanisms, which play a positive role in the repair of bone defects and provide strong support for the regeneration and repair of bone tissue.
骨缺损是指由于外伤、骨折、感染等导致的骨组织丢失。这种损失可能导致骨折不愈合、骨缺损或骨缺乏,严重影响患者的生活质量,甚至导致功能障碍和残疾。虽然手术修复是常见的治疗方式,但手术过程复杂,术后恢复期长,存在一定的手术风险,如感染、出血等。富血小板血浆(PRP)作为一种新的治疗方法,在骨缺损修复中显示出巨大的潜力。PRP中含有丰富的生长因子,如血小板源性生长因子(PDGF)、转化生长因子-β (TGF-β)、血管内皮生长因子(VEGF)等,可通过多种机制,如释放生长因子、促进血管生成、抑制炎症反应、募集活化细胞等机制,对骨缺损修复产生有益作用。对骨缺损的修复起到积极的作用,为骨组织的再生和修复提供有力的支持。
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引用次数: 0
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Regenerative Therapy
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