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Microenvironment-directed chondrogenesis of adipose-derived mesenchymal stem cells in hyaline, elastic, and fibrocartilage in vivo. 体内透明软骨、弹性软骨和纤维软骨中脂肪来源的间充质干细胞的微环境定向软骨形成。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-03-13 DOI: 10.1007/s10561-026-10219-1
Yi Han, Hao Ma, Jingyi Chen, Liuhanghang Cheng, Ke Li, Baolin Zhang, Peiru Min

Cartilage exhibits remarkable subtype diversity-hyaline, fibrocartilage, and elastic-each with unique extracellular matrix architecture and mechanical function. Despite the clinical promise of adipose-derived mesenchymal stem cells (ADMSCs) for cartilage regeneration, whether distinct in vivo cartilage microenvironments can instruct ADMSC differentiation toward corresponding subtypes remains poorly defined. Green fluorescent protein-labeled human ADMSCs were encapsulated in a fibrin hydrogel and implanted into three representative cartilage sites-auricular (elastic), articular (hyaline), and meniscal (fibrocartilage)-in an immunodeficient rat model. Regenerated tissues were harvested at 4 weeks for histology (H&E), immunofluorescence analysis of hyaline (COL II, aggrecan), fibrocartilage (COL I, tenomodulin), and elastic (fibrillin-1, elastin) markers, and RT-PCR quantification of lineage-associated gene expression. ADMSCs survived and engrafted within all three microenvironments. Articular cartilage implants exhibited strong hyaline-like differentiation, characterized by intense COL II and aggrecan expression and upregulation of SOX9, COL2A1, and ACAN. Meniscal implants instead displayed a fibrocartilage-like profile with robust COL I and tenomodulin expression and elevated COL1A1, TNMD, and SCX transcripts. In contrast, auricular cartilage implants showed negligible expression of hyaline, fibrocartilage, or elastic markers, accompanied by global downregulation of chondrogenic and elastogenic genes. These results demonstrate that local cartilage niches exert distinct instructive effects on ADMSC fate: articular and meniscal environments effectively guide hyaline- and fibrocartilage-like differentiation, whereas the auricular niche under the tested conditions fails to support elastic or hyaline lineage commitment. Our findings highlight the decisive role of the tissue microenvironment in modulating ADMSC differentiation and underscore the need for bioengineered, niche-mimetic scaffolds to achieve subtype-specific cartilage regeneration-particularly for complex elastic tissues such as the auricle.

软骨表现出显著的亚型多样性——透明软骨、纤维软骨和弹性软骨——每一种都有独特的细胞外基质结构和机械功能。尽管脂肪源性间充质干细胞(ADMSCs)用于软骨再生的临床前景很好,但体内不同的软骨微环境是否能指导ADMSCs向相应亚型分化仍不清楚。绿色荧光蛋白标记的人ADMSCs被包裹在纤维蛋白水凝胶中,并植入免疫缺陷大鼠模型的三个代表性软骨部位——耳廓(弹性)、关节(透明)和半月板(纤维软骨)。在4周时收获再生组织进行组织学(H&E),免疫荧光分析透明蛋白(COL II,聚集蛋白),纤维软骨(COL I, tenomodulin)和弹性(fibrin -1,弹力蛋白)标记物,RT-PCR定量分析谱系相关基因表达。ADMSCs在三种微环境中均能存活并移植。关节软骨植入物表现出强烈的透明样分化,其特征是强烈的COL II和聚集蛋白表达以及SOX9、COL2A1和ACAN的上调。相反,半月板植入物显示出纤维软骨样的轮廓,COL I和tenomodulin表达强劲,COL1A1、TNMD和SCX转录物升高。相比之下,耳廓软骨植入物的透明蛋白、纤维软骨或弹性标记物的表达可以忽略不计,并伴有软骨和弹性基因的整体下调。这些结果表明,局部软骨生态位对ADMSC的命运具有明显的指导作用:关节和半月板环境有效地引导透明软骨样和纤维软骨样分化,而在所测试条件下的耳穴生态位不支持弹性或透明软骨谱系的承诺。我们的研究结果强调了组织微环境在调节ADMSC分化中的决定性作用,并强调了生物工程、仿生支架实现亚型特异性软骨再生的必要性,特别是对于复杂的弹性组织,如耳廓。
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引用次数: 0
Willingness to bone allograft donation and transplantation in sub-Saharan Africa: a multi-country cross-sectional study. 撒哈拉以南非洲地区同种异体骨捐献和移植意愿:一项多国横断面研究。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-03-13 DOI: 10.1007/s10561-026-10220-8
Cédric Dongmo Mayopa, Aya Adelaïde Natacha Kouassi, Randy Buzisa Mbuku, André Claude Mbaga, Samuel Nkubamanu, Richard Ndambo, Gaspary Fodjeu, Jeholive Munoko, Loïc Fonkoue, Freddy Bombah, Pierre Louis Docquier, Thomas Schubert, Olivier Cornu

Bone is the second most frequently transplanted human tissue worldwide. In sub-Saharan Africa, donor and recipient consent for bone allograft donation and transplantation remains uncertain due to diverse sociocultural, religious, and socioeconomic contexts. This study assessed public attitudes toward bone allograft donation and transplantation in Cameroon, the Democratic Republic of Congo, and the Republic of Côte d'Ivoire to support the planning and implementation of bone banking programs. A multicountry cross-sectional survey was conducted between January and December 2024. Six hundred adults were recruited using a non-probabilistic, stratified convenience sampling in urban and rural settings. After informed consent, participants completed a structured questionnaire, self-administered whenever possible capturing sociodemographic data, willingness to donate and receive bone allografts, and perceived reasons for refusal. Descriptive analyses and univariate and multivariate logistic regression models were used to identify factors associated with willingness. The mean age of participants was 36.2 years. Overall, 72.5% reported willingness to donate bone allografts and 72.8% reported willingness to accept transplantation. The main reasons for refusal included belief-related or religious considerations, fear of trafficking, and expectations of financial compensation. In multivariable analyses, willingness to donate was independently associated with country of residence, religious affiliation, and occupation, while willingness to accept transplantation was associated with country and religious affiliation. Willingness to donate and receive bone allografts in the surveyed sub-Saharan Africa settings was relatively high although marked heterogeneity existed between countries. Key barriers include religious beliefs, mistrust of health systems, and socioeconomic vulnerability. The development of bone banking programs in the region will require culturally sensitive education, transparent governance, and active community engagement to transform expressed willingness into effective donation practices.

骨是世界上第二大最常移植的人体组织。在撒哈拉以南非洲,由于不同的社会文化、宗教和社会经济背景,供体和受者对同种异体骨移植捐赠和移植的同意仍然不确定。本研究评估了喀麦隆、刚果民主共和国和Côte科特迪瓦共和国公众对同种异体骨移植捐赠和移植的态度,以支持骨库项目的规划和实施。在2024年1月至12月期间进行了多国横断面调查。在城市和农村地区采用非概率分层方便抽样方法招募了600名成年人。在知情同意后,参与者完成了一份结构化问卷,尽可能地进行自我管理,以获取社会人口统计数据,捐献和接受同种异体骨移植的意愿,以及拒绝的感知原因。使用描述性分析和单变量和多变量逻辑回归模型来确定与意愿相关的因素。参与者的平均年龄为36.2岁。总体而言,72.5%的人表示愿意捐献同种异体骨移植,72.8%的人表示愿意接受移植。拒绝的主要原因包括与信仰或宗教有关的考虑、害怕被贩运以及期望获得经济赔偿。在多变量分析中,捐献意愿与居住国、宗教信仰和职业独立相关,而接受移植意愿与国家和宗教信仰相关。在接受调查的撒哈拉以南非洲地区,捐献和接受同种异体骨移植的意愿相对较高,尽管各国之间存在明显的异质性。主要障碍包括宗教信仰、对卫生系统的不信任以及社会经济脆弱性。该地区骨库项目的发展需要具有文化敏感性的教育、透明的治理和积极的社区参与,以将表达的意愿转化为有效的捐赠实践。
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引用次数: 0
Quantification and characterization of collagen in experimentally induced wounds treated with different types of platelet-rich plasma gel. 不同类型富血小板血浆凝胶治疗实验性创面胶原蛋白的定量和表征。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-03-04 DOI: 10.1007/s10561-026-10215-5
G Haro de Melo, F M Moreira, G G Mori, L F Bento, D V Barrionuevo, C B Laposy, R Giuffrida, A F F Rodrigues, G A T Ozaki, D A F da Silva, F L Pacagnelli, R M B Nogueira

Due to its high concentration of growth factors, platelet-rich plasma (PRP) has become the subject of much research, either as an isolated or adjuvant treatment for wound repair. The fractal dimension has been used as an innovative method for the characterization and quantification of tissue structural alterations without any interference from the evaluator. The objective of this study was characterizing collagen types I and III in experimentally induced wounds and treated with different PRP sources by means of fractal dimension and other histological analyzes using blades stained with picrocirius-red and hematoxylin-eosin (HE). In statistical analysis, the variables presented a non-parametric distribution; thus, Mann-Whitney and Kruskall-Wallis tests (p < 0,05) were performed using the Student-Newman-Keuls method. It was observed an increase of the collagen fibers by measuring the area with Threshold Color in the different treatments, especially with autologous PRP (p = 0.009) and heterologous PRP (p = 0.016). The fractal dimension of type I collagen had a significant increase for the autologous group (p = 0.028) in relation to the control, but, on average (p < 0.05), type III collagen was higher than type I. Fractal dimension was efficient to separately characterize type I and type III collagen fibers. In this study, collagenization was higher in autologous when compared to heterologous and homologous PRP treatments.

富血小板血浆(PRP)由于其具有高浓度的生长因子,无论是作为一种孤立的还是辅助的伤口修复治疗方法,都已成为研究的热点。分形维数已被用作一种创新的方法来表征和量化组织结构的变化,而不受评估者的任何干扰。本研究的目的是通过分形维数和其他组织学分析,利用微红和苏木精伊红(HE)染色的叶片来表征实验诱导伤口和不同PRP来源处理的I型和III型胶原。在统计分析中,变量呈非参数分布;因此,Mann-Whitney检验和Kruskall-Wallis检验(p
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引用次数: 0
Enhancing cadaver preparation protocol to reduce bacterial contamination in musculoskeletal allografts: a comparative study of battlefield fatalities and general population donors. 加强尸体准备程序以减少同种异体肌肉骨骼移植中的细菌污染:战场死亡和一般人群供体的比较研究。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-25 DOI: 10.1007/s10561-026-10208-4
Helit Cohen, Moti Harats, Ron Burshtein, Alina Levi, Daniel Dothan, Marina BenShoshan, Michelle Cleary, Rachel Kornhaber, Josef Haik, Ayelet Di Segni

Musculoskeletal allografts are becoming increasingly essential in orthopaedic and reconstructive surgery. A significant source of these allografts is tissues retrieved from deceased donors. While contributing substantially to the pool of allografts, these tissues are at increased risk of bacterial contamination. This risk is further amplified when tissues are procured from field casualties. In this study, we performed a side-by-side retrospective comparison of contamination rates in tissues retrieved from the general population and battlefield mortalities, representing field casualties. In response to the rising incidence of contaminated tissues obtained from field casualty donors, we implemented a more rigorous pre-operative washing protocol designed to maximize sterility. This protocol modification led to a significant decrease in the contamination ratio of tissues retrieved from field casualties. Our findings suggest that current pre-operative cadaver preparation guidelines may need to be reconsidered for tissue donations following unsanitary condition mortalities. Furthermore, these findings strongly suggest that field surgeries would benefit from a surgical pre-operative preparation designed specifically for incidents such as battlefields, accidents or mass casualty incident areas to minimize post-operative infections and improve surgical outcomes.

同种异体肌肉骨骼移植在骨科和重建手术中变得越来越重要。这些同种异体移植物的一个重要来源是从已故供体中取出的组织。虽然这些组织对同种异体移植物有很大贡献,但它们受到细菌污染的风险增加。当从战地伤员身上获取组织时,这种风险进一步扩大。在这项研究中,我们对从普通人群和战场死亡率中提取的组织中的污染率进行了并排回顾性比较,代表了战场伤亡。为了应对从战地伤员供体获得的受污染组织的发生率上升,我们实施了更严格的术前清洗方案,旨在最大限度地提高无菌性。这一协议的修改导致从战场伤亡人员中提取的组织的污染率显著降低。我们的研究结果表明,目前的术前尸体准备指南可能需要重新考虑在不卫生条件下死亡后的组织捐赠。此外,这些研究结果强烈表明,野外手术将受益于专门为战场、事故或大规模伤亡事件地区等事件设计的手术术前准备,以减少术后感染并改善手术结果。
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引用次数: 0
Scaffold Design: A Review of Material and Immune Modulation in Bone Tissue Engineering. 支架设计:骨组织工程中材料与免疫调节的综述。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-20 DOI: 10.1007/s10561-026-10212-8
Mohamed Selim, Sleem A Farag, Gamal T Abdel-Jaber, Abdalla Abdal-Hay, Hamouda M Mousa

With the growing population and increased life expectancy, there has been a significant rise in orthopedic fractures and pathologies, leading to a heightened demand for effective orthopedic solutions. Bone tissue engineering (BTE) has emerged as a promising approach, employing scaffolds to regenerate bone tissue. This review highlights that successful material design for BTE requires a comprehensive understanding of the composition, structure, and biomechanics of natural bone. It also necessitates the careful selection of biomimetic natural or tunable synthetic materials, including polymers, bioceramics, metals, and composites. Furthermore, optimizing the physical, mechanical, and chemical properties of scaffolds is crucial, as these factors influence cell adhesion, proliferation, and differentiation. Special attention is given to the interaction between scaffolds and the host immune system, including the strategic incorporation of bioactive molecules and immunoregulatory cells. This holistic approach aims to engineer scaffolds that not only meet structural and functional demands but also foster an immune-compatible environment to enhance bone regeneration effectively. Careful selection of effective immunomodulation strategies for 3D scaffolds is crucial for creating a supportive immune microenvironment without negative effects. Various approaches can enhance the immune response, including incorporating smart nanomaterials into the surface of scaffolds, which contribute to immunomodulation, angiogenesis, and osteogenesis. Using stem cells for regenerating damaged bone tissue also improves the scaffold's immune response. Moreover, ionic and molecular doping are effective methods used to enhance immune response of scaffold in (BET), where specific ions like magnesium, zinc, and silicon are added to improve bioactivity and immune modulation capabilities. Finally, Wnt/β-catenin signaling pathway can be activated by integrating lithium into the scaffold surface, as lithium has anti-inflammatory properties and promotes bone formation by activating these pathways.

随着人口的增长和预期寿命的延长,骨科骨折和病理的显著增加,导致对有效骨科解决方案的需求增加。骨组织工程(BTE)是一种很有前途的方法,利用支架来再生骨组织。这篇综述强调,成功的BTE材料设计需要对天然骨的组成、结构和生物力学有全面的了解。它还需要仔细选择仿生天然或可调合成材料,包括聚合物,生物陶瓷,金属和复合材料。此外,优化支架的物理、机械和化学性质是至关重要的,因为这些因素影响细胞的粘附、增殖和分化。特别关注支架与宿主免疫系统之间的相互作用,包括生物活性分子和免疫调节细胞的战略性结合。这种整体方法的目的是设计支架,不仅满足结构和功能要求,而且还培养免疫兼容的环境,以有效地增强骨再生。为3D支架精心选择有效的免疫调节策略对于创造无负面影响的支持性免疫微环境至关重要。多种方法可以增强免疫反应,包括将智能纳米材料结合到支架表面,这有助于免疫调节,血管生成和成骨。使用干细胞再生受损的骨组织也能改善支架的免疫反应。此外,离子和分子掺杂是增强支架免疫反应的有效方法,通过添加特定离子如镁、锌、硅来提高支架的生物活性和免疫调节能力。最后,将锂整合到支架表面可以激活Wnt/β-catenin信号通路,因为锂具有抗炎特性,并通过激活这些通路促进骨形成。
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引用次数: 0
Optimization of the microbiological quality control validation of corneal medium using a clinical C. acnes isolate. 临床痤疮芽孢杆菌分离株对角膜培养基微生物质量控制的优化验证。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-19 DOI: 10.1007/s10561-026-10211-9
Philipp Maximilian Maurer, Gefion Franke, Johannes K Knobloch

The microbiological quality of corneal tissue for transplantation must be monitored in a validated procedure complying with the European Pharmacopoeia (Ph. Eur.). An automated culture system is used to detect test strains in the presence of the medium. The Ph. Eur. mentioned C. acnes ATCC 11827 strain has allegedly been isolated from skin. This strain is known to display variable growth in routine matrix validation. As the Ph. Eur. also opens the use of clinical isolates, this study analyzed the use of clinical isolates for matrix validation.We compared the time-to-detection (TTD) in absence and presence of cornea organ culture medium (cocm) of 24 C. acnes strains, preferring clinical isolates, in an automated culture system.In the first step clinical strains (n=23) were examined, thus 4 slow-growing (TTD 305,1-336 h), 5 intermediate-fast-growing (TTD 250,1-305 h), 5 fast-growing strains (TTD 164,3-250 h) and nine non-blood-culture-detectable strains (TTD>336 h) were identified. Seven strains showed a reproducible growth signal in cocm-absence. In presence of cocm, three strains (CA02, CA10, CA22) showed a reproducible growth signal, while the reference strain was not blood-culture-detectable (bcd) in four of five experiments. The strain with the preferred growth characteristics (DSM 117854) was tested according to the Ph. Eur. conditions and showed bcd growth in all measurements (n=5) in presence of medium, in contrast to the reference strain.The use of a clinical isolate of C. acnes could improve matrix validation of cocm quality control testing and thus the care of cornea-transplant-patients. C. acnes DSM 117854 provides an isolate that promises more reliable results in matrix validation.

移植角膜组织的微生物质量必须在符合欧洲药典(Ph. Eur.)的有效程序中进行监测。自动培养系统用于在培养基存在的情况下检测试验菌株。博士学位。提到的痤疮C. ATCC 11827菌株据称是从皮肤中分离出来的。已知该菌株在常规基质验证中显示可变生长。作为欧洲哲学博士。同时也开启了临床分离株的使用,本研究分析了使用临床分离株进行基质验证。我们比较了24株痤疮C.菌株在自动培养系统中角膜器官培养基(cocm)缺失和存在时的检测时间(TTD),更倾向于临床分离株。第一步检测临床菌株23株,其中4株生长缓慢(TTD 305,1 ~ 336 h), 5株中快速生长(TTD 250,1 ~ 305 h), 5株快速生长(TTD 164,3 ~ 250 h), 9株血培养不可检出(TTD bb0 ~ 336 h)。7株菌株在不加玉米的情况下表现出可复制的生长信号。cocm存在时,3株菌株(CA02、CA10、CA22)表现出可重复的生长信号,而参比菌株在5个实验中有4个没有血培养可检出(bcd)。对具有首选生长特性的菌株(DSM 117854)进行了试验。与参考应变相比,在介质存在的情况下,所有测量结果(n=5)均显示BCD增长。痤疮C.临床分离物的使用可以提高角膜移植患者角膜质量控制检测的基质验证,从而提高角膜移植患者的护理水平。C.痤疮DSM 117854提供了一个分离,承诺在矩阵验证更可靠的结果。
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引用次数: 0
Global research trends in allogenic bone and bone banking in orthopaedics: a 25-year bibliometric analysis (2000-2025). 骨科中同种异体骨和骨库的全球研究趋势:25年文献计量分析(2000-2025)。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-10 DOI: 10.1007/s10561-026-10214-6
Anil Regmi, Surakshya Baral

Allogenic bone grafting and bone banking have become vital components of modern orthopaedic reconstruction, addressing bone loss following trauma, infection, tumor resection, and revision arthroplasty. Despite expanding clinical use, a comprehensive overview of global research productivity and collaboration in this domain has not been previously undertaken. A bibliometric analysis was conducted using the Scopus database (2000-2025) with defined search terms related to bone banking and allogenic bone grafting in orthopaedics. Data were analyzed using Scopus analytics and VOSviewer for publication trends, source impact, geographic distribution, authorship, funding patterns, and keyword co-occurrence networks. A total of 3497 documents were identified, showing steady publication growth. The majority were original research articles (79.2%). The United States led in publication output (37.7%), followed by China and Italy. Clinical Orthopaedics and Related Research and Spine were the most productive journals. Keyword mapping revealed core themes in revision arthroplasty, spinal fusion, limb reconstruction, and bone defect management. Global research on allogenic bone and bone banking demonstrates robust growth, interdisciplinary collaboration, and emerging regional contributions. Future efforts should emphasize standardization, outcome-based studies, and integration of biomaterials and regenerative technologies to enhance the safety and sustainability of bone banking worldwide.

同种异体骨移植和骨库已成为现代骨科重建的重要组成部分,可解决创伤、感染、肿瘤切除和翻修关节成形术后的骨丢失问题。尽管临床应用不断扩大,但此前尚未对该领域的全球研究生产力和合作进行全面概述。使用Scopus数据库(2000-2025)进行文献计量学分析,并定义与骨科中骨库和同种异体骨移植相关的搜索词。使用Scopus分析和VOSviewer对数据进行分析,包括出版趋势、来源影响、地理分布、作者身份、资助模式和关键词共现网络。共发现3497篇文献,发文量稳步增长。以原创研究论文居多(79.2%)。美国在出版物产出方面领先(37.7%),其次是中国和意大利。临床骨科及相关研究和脊柱是最多产的期刊。关键词映射揭示了翻修关节置换术、脊柱融合、肢体重建和骨缺损处理的核心主题。同种异体骨和骨库的全球研究显示出强劲的增长、跨学科合作和新兴的区域贡献。未来的努力应强调标准化,基于结果的研究,以及生物材料和再生技术的整合,以提高全球骨库的安全性和可持续性。
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引用次数: 0
Engineered exosomes for targeted bone regeneration: design, delivery, and functionalization. 靶向骨再生的工程外泌体:设计、输送和功能化。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-10 DOI: 10.1007/s10561-026-10213-7
Asrin Emami, Iman Menbari Oskouie

Bone regeneration remains a major clinical challenge due to the limited healing capacity of large bone defects and the limitations of conventional grafting or cell-based therapies. Exosomes, nanosized extracellular vesicles secreted by diverse cell types, have emerged as promising cell-free mediators of osteogenesis, angiogenesis, and immune regulation. However, the therapeutic efficacy of native exosomes is constrained by low yield, rapid clearance, and limited targeting. Because effective bone regeneration is inherently multi-factorial-requiring biomechanical stability, vascularization, and an instructive ECM and cellular microenvironment-engineered exosomes should be regarded as enabling components within integrated regenerative systems rather than a standalone solution. Recent advances in engineered exosomes (EExos) have opened new frontiers in bone tissue regeneration by enabling precise design, biofunctionalization, and targeted delivery. Engineering strategies-ranging from genetic modification of donor cells to chemical conjugation, hybrid nanocarrier formation, and controlled cargo loading-have been employed to enhance the osteoinductive and osteoconductive potential of exosomes. Furthermore, incorporation of EExos into smart delivery systems, such as hydrogel scaffolds, 3D-printed matrices, and bone-targeting ligands, offers sustained release and localized therapeutic effects within the bone microenvironment. This review comprehensively summarizes the latest developments in the design, delivery, and functional optimization of EExos for bone regeneration. Mechanistic insights into their roles in promoting bone remodeling, angiogenesis, and immune modulation are discussed alongside current translational progress, manufacturing challenges, and regulatory considerations. Finally, emerging directions-such as AI-assisted exosome engineering, CRISPR-based programming, and bioprinting-integrated therapies-are highlighted as transformative pathways toward personalized and clinically translatable bone regenerative medicine.

骨再生仍然是一个主要的临床挑战,由于大骨缺损的愈合能力有限,传统的移植或细胞为基础的治疗的局限性。外泌体是由多种细胞类型分泌的纳米级细胞外囊泡,已成为成骨、血管生成和免疫调节的有前途的无细胞介质。然而,天然外泌体的治疗效果受到低产量、快速清除和靶向性有限的限制。由于有效的骨再生本质上需要多因素的生物力学稳定性、血管化、指导性ECM和细胞微环境,因此工程外泌体应被视为集成再生系统中的使能组件,而不是一个独立的解决方案。工程外泌体(EExos)的最新进展通过实现精确设计、生物功能化和靶向递送,为骨组织再生开辟了新的领域。工程策略-从供体细胞的遗传修饰到化学偶联,杂交纳米载体形成和控制货物装载-已被用于增强外泌体的骨诱导和骨传导潜力。此外,将EExos结合到智能递送系统中,如水凝胶支架、3d打印基质和骨靶向配体,可在骨微环境中提供持续释放和局部治疗效果。本文综述了骨再生EExos的设计、交付和功能优化方面的最新进展。本文讨论了它们在促进骨重塑、血管生成和免疫调节中的作用的机制,以及当前的转化进展、制造挑战和监管考虑。最后,新兴方向——如人工智能辅助外泌体工程、基于crispr的编程和生物打印集成疗法——被强调为个性化和临床可翻译的骨再生医学的变革途径。
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引用次数: 0
Impact of donor-recipient gender mismatch on outcomes in Descemet membrane endothelial keratoplasty (DMEK). 供体-受体性别不匹配对视网膜膜内皮角膜移植术(DMEK)结果的影响。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-10 DOI: 10.1007/s10561-026-10210-w
Zoe Eckly, Andre M Trouvain, Maria Della Volpe-Waizel, Clara E Englisch, Peter Szurman, Berthold Seitz, Fabian Fries, Annekatrin Rickmann

Purpose: Previous studies have suggested that H-Y antigens may influence immunological outcomes in corneal transplantation. This study analyses the influence of donor-recipient gender mismatch in DMEK on postoperative outcomes.

Methods: This single-center retrospective study included 2521 eyes (1712 patients) that underwent DMEK between January 2012 and December 2021. Patients were divided into four groups according to donor-to-recipient gender combinations (male-to-female, male-to-male, female-to-male, female-to-female) and were compared in terms of graft failure rate, visual acuity (VA), central corneal thickness (CCT), and endothelial cell count (ECC) preoperatively and at 1, 12 and 36 months postoperatively, as well as in terms of postoperative complications.

Results: Of the 2521 cases, 1647 (65%) were sex-mismatched (male-to-female or female-to-male) and 874 (35%) were sex-matched (female-to-female or male-to-male). Intraoperative preparation time of the grafts (p = 0.78) and difficulties in the intraoperative handling (p = 0.43) were comparable in all groups. Re-bubbling or re-keratoplasty was required with comparable frequency (p = 0.84; p = 0.61 respectively). The occurence of primary or secondary graft failure was not statistically significant different between the groups (p = 0.57). No confirmed case of immunological graft rejection occurred. Functional postoperative outcomes for ECC (p = 0.18 after 1 month, p = 0.13 after 12 months, p = 0.27 after 36 months), CCT (p = 0.58 after 4-6 weeks, p = 0.82 after 12 months, p = 0.78 after 36 months) and VA (p = 0.64 after 4-6 weeks, p = 0.47 after 12 months, p = 0.39 after 36 months) were comparable in all groups at the follow-up.

Conclusions: In this retrospective cohort, no documented immune graft rejection was observed, and sex mismatch did not influence intraoperative handling or postoperative interventions. However, prospective studies with standardized immunologic assessment are needed to clarify the role of donor-recipient sex mismatch in DMEK outcomes.

目的:以往的研究表明,H-Y抗原可能影响角膜移植的免疫结果。本研究分析DMEK供受体性别不匹配对术后预后的影响。方法:这项单中心回顾性研究纳入了2012年1月至2021年12月期间接受DMEK手术的2521只眼(1712例患者)。根据供体-受体性别组合(男对女、男对男、女对男、女对男、女对女)将患者分为四组,比较术前、术后1、12、36个月的移植物失败率、视力(VA)、角膜中央厚度(CCT)、内皮细胞计数(ECC)及术后并发症。结果:2521例中,性别不匹配(男对女、女对男)1647例(65%),性别不匹配(女对女、男对男)874例(35%)。两组患者术中移植物准备时间(p = 0.78)和术中处理困难程度(p = 0.43)具有可比性。需要重新冒泡或重新角膜移植的频率相当(p = 0.84; p = 0.61)。两组间原发性和继发性移植物衰竭发生率无统计学差异(p = 0.57)。未发生确诊的移植物免疫排斥反应。ECC(1个月后p = 0.18, 12个月后p = 0.13, 36个月后p = 0.27)、CCT(4-6周后p = 0.58, 12个月后p = 0.82, 36个月后p = 0.78)和VA(4-6周后p = 0.64, 12个月后p = 0.47, 36个月后p = 0.39)的术后功能结果在随访时各组间具有可比较性。结论:在这个回顾性队列中,没有观察到有记录的免疫移植排斥反应,性别不匹配也没有影响术中处理或术后干预。然而,需要标准化免疫评估的前瞻性研究来阐明供体-受体性别不匹配在DMEK结果中的作用。
{"title":"Impact of donor-recipient gender mismatch on outcomes in Descemet membrane endothelial keratoplasty (DMEK).","authors":"Zoe Eckly, Andre M Trouvain, Maria Della Volpe-Waizel, Clara E Englisch, Peter Szurman, Berthold Seitz, Fabian Fries, Annekatrin Rickmann","doi":"10.1007/s10561-026-10210-w","DOIUrl":"10.1007/s10561-026-10210-w","url":null,"abstract":"<p><strong>Purpose: </strong>Previous studies have suggested that H-Y antigens may influence immunological outcomes in corneal transplantation. This study analyses the influence of donor-recipient gender mismatch in DMEK on postoperative outcomes.</p><p><strong>Methods: </strong>This single-center retrospective study included 2521 eyes (1712 patients) that underwent DMEK between January 2012 and December 2021. Patients were divided into four groups according to donor-to-recipient gender combinations (male-to-female, male-to-male, female-to-male, female-to-female) and were compared in terms of graft failure rate, visual acuity (VA), central corneal thickness (CCT), and endothelial cell count (ECC) preoperatively and at 1, 12 and 36 months postoperatively, as well as in terms of postoperative complications.</p><p><strong>Results: </strong>Of the 2521 cases, 1647 (65%) were sex-mismatched (male-to-female or female-to-male) and 874 (35%) were sex-matched (female-to-female or male-to-male). Intraoperative preparation time of the grafts (p = 0.78) and difficulties in the intraoperative handling (p = 0.43) were comparable in all groups. Re-bubbling or re-keratoplasty was required with comparable frequency (p = 0.84; p = 0.61 respectively). The occurence of primary or secondary graft failure was not statistically significant different between the groups (p = 0.57). No confirmed case of immunological graft rejection occurred. Functional postoperative outcomes for ECC (p = 0.18 after 1 month, p = 0.13 after 12 months, p = 0.27 after 36 months), CCT (p = 0.58 after 4-6 weeks, p = 0.82 after 12 months, p = 0.78 after 36 months) and VA (p = 0.64 after 4-6 weeks, p = 0.47 after 12 months, p = 0.39 after 36 months) were comparable in all groups at the follow-up.</p><p><strong>Conclusions: </strong>In this retrospective cohort, no documented immune graft rejection was observed, and sex mismatch did not influence intraoperative handling or postoperative interventions. However, prospective studies with standardized immunologic assessment are needed to clarify the role of donor-recipient sex mismatch in DMEK outcomes.</p>","PeriodicalId":9723,"journal":{"name":"Cell and Tissue Banking","volume":"27 1","pages":"10"},"PeriodicalIF":2.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dimethyl fumarate as an immunomodulatory enhancer of adipose-derived mesenchymal stem cells: therapeutic implications. 富马酸二甲酯作为脂肪来源的间充质干细胞的免疫调节增强剂:治疗意义。
IF 2 4区 医学 Q4 CELL BIOLOGY Pub Date : 2026-02-10 DOI: 10.1007/s10561-026-10209-3
Leila Abdullahi-Keivani, Mina Montazeri, Hossein Rahavi, Mohammad Taher Tahoori

Adipose-drive stem cells (ASCs) are similar to Mesenchymal stem cells (MSCs), which are considered as multipotent progenitors that have capable of immunomodulation, self-renewal and differentiation into multiple cell lineages that can be used in cancer therapy or immune diseases. Dimethyl fumarate (DMF) is one of the important drugs with modulating function for treatment of various immune disease. The primary aim of this study was to investigate how dimethyl fumarate influences the immunomodulatory profile and functional properties of adipose‑derived mesenchymal stem cells under inflammatory conditions. Adipose-stimulating stem cells (ASCs) were isolated from the abdominal adipose tissue of ten patients via liposuction, and DMF was added after inducing inflammatory conditions with inflammatory cytokines such as IFN-γ and TNF-α. Cell culture and RT-PCR were performed to measure the expression of immunomodulatory factors such as Galectin-1/3, HGF, HO-1, CXCL-8, and IL-6. Flow cytometry for mesenchymal stem cell nature and confirmation was done. Fat and bone staining was performed to test the functional differentiation of these cells. ASCs treated with DMF at 0.01-100 μM concentration at 2 days showed the enhancement of CXCL-8 and IL-6 gene expression notably, whereas, HGF, and Galectin-1 reduced. Moreover, Galectin-3 and HO-1 depicted no significant difference compared to the control group. Further, Alizarin Red and Oil Red staining verified the change of MSCs toward adipose and osteogenic differentiation. ASCs are positive for markers including CD73+, CD90+, and CD105+ antigens by abs staining conjugated to fluorescence dye. Our study confirmed that ASCs combined with DMF have increasingly important roles through immune-modulatory properties by secreting mediators, which can suppress, improve, alter, or change the microenvironment of disease. Despite ongoing progress, the underlying stimulatory and regulatory mechanisms remain incompletely understood. The gap between pre‑clinical findings and clinical applications highlights the need for further investigation. Extensive research is still required to elucidate how therapeutic interventions achieve efficacy, ensure safety, and identify optimal strategies for targeting different organs in combination with other pharmacological agents.

脂肪驱动干细胞(ASCs)类似于间充质干细胞(MSCs),被认为是多能祖细胞,具有免疫调节、自我更新和分化成多细胞系的能力,可用于癌症治疗或免疫疾病。富马酸二甲酯(DMF)是治疗多种免疫疾病的重要调节药物之一。本研究的主要目的是研究富马酸二甲酯如何影响炎症条件下脂肪源性间充质干细胞的免疫调节特征和功能特性。通过吸脂法从10例患者腹部脂肪组织中分离脂肪刺激干细胞(ASCs),在IFN-γ、TNF-α等炎症因子诱导炎症后加入DMF。通过细胞培养和RT-PCR检测半乳糖凝集素-1/3、HGF、HO-1、CXCL-8、IL-6等免疫调节因子的表达。流式细胞术检测间充质干细胞的性质并证实。脂肪和骨染色检测这些细胞的功能分化。0.01 ~ 100 μM DMF处理ASCs 2 d后,CXCL-8和IL-6基因表达明显增强,HGF和半乳糖凝集素-1表达明显降低。此外,半乳糖凝集素-3和HO-1与对照组相比无显著差异。茜素红和油红染色进一步证实了MSCs向脂肪和成骨分化的变化。通过与荧光染料结合的abs染色,ASCs对CD73+、CD90+和CD105+抗原标记物呈阳性。我们的研究证实ASCs联合DMF通过分泌介质的免疫调节特性发挥越来越重要的作用,这些介质可以抑制、改善、改变或改变疾病的微环境。尽管正在取得进展,但潜在的刺激和调节机制仍然不完全清楚。临床前研究结果和临床应用之间的差距突出了进一步研究的必要性。目前仍需要大量的研究来阐明治疗干预如何达到疗效,确保安全性,并确定与其他药物联合针对不同器官的最佳策略。
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