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Fabrication of stacked polymer cluster coatings via an evaporation-assisted grafting strategy for inducing endothelial cell network formation 通过蒸发辅助接枝策略制备堆叠聚合物簇涂层以诱导内皮细胞网络形成。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.11.056
Shuxiang Zhang , Chuchu Tang , Ningyue Deng , Xiangyu Dong , Jiacheng Lei , Zhiqin Chu , Qiang Wei
The clustered polymer structures formed by grafting polymer brushes greatly enhance biomaterial surface properties. However, their nanoscale thickness and gaps caused by steric hindrance between clusters often lead to instability, limiting their applications. This study exploits the self-assembly of benzophenone-functionalized polymers into clusters in non-aqueous solvents, which are subsequently “frozen” and anchored to the surface through an evaporation-assisted grafting strategy to form stable, stacked polymer cluster coatings. This process is related to the rate of solvent removal and the proportion of benzophenone in the copolymer. This unique structure yields antifouling coatings with superior, sustained resistance to contaminants due to its closely stacked clusters. Moreover, this method can be extended to the preparation of stacked heparin-mimetic polymer cluster coatings that exhibit native binding of endothelial cell growth factors, inducing endothelial network formation, a capability not achievable with traditional methods. In vivo, the coating reduced inflammatory encapsulation and facilitated rapid endothelial organization and vessel-like remodeling at the implant-tissue interface. This strategy highlights the pivotal role of interfacial architectures and molecular interactions in guiding cellular behaviour, providing a distinct perspective on the development of high-performance coatings.

Statement of Significance

Our study introduces an evaporation-assisted grafting strategy to fabricate stacked polymer cluster coatings, overcoming the instability of traditional polymer brushes. These coatings demonstrate exceptional antifouling performance and support the versatile integration of functional components. Notably, the resulting stacked heparin-mimetic polymer coatings effectively induce endothelial network formation, rivalling commercial Matrigel-based assays. By harnessing precisely engineered interfacial structures and molecular interactions, this scalable, low-cost approach offers a solution for biomaterial surface design in tissue engineering applications.
接枝聚合物刷形成的簇状聚合物结构大大提高了生物材料的表面性能。然而,它们的纳米级厚度和团簇之间的位阻引起的间隙往往导致不稳定,限制了它们的应用。本研究利用二苯甲酮功能化聚合物在非水溶剂中自组装成簇,随后通过蒸发辅助接枝策略“冻结”并固定在表面,形成稳定的堆叠聚合物簇涂层。这一过程与溶剂去除率和二苯甲酮在共聚物中的比例有关。这种独特的结构产生防污涂层优越,持续抵抗污染物,由于其紧密堆叠簇。此外,该方法可以扩展到制备堆叠的模拟肝素聚合物簇涂层,该涂层具有内皮细胞生长因子的天然结合,诱导内皮网络的形成,这是传统方法无法实现的。在体内,涂层减少了炎症包封,促进了种植体-组织界面的内皮组织和血管样重塑。这一策略强调了界面结构和分子相互作用在指导细胞行为中的关键作用,为高性能涂层的发展提供了独特的视角。意义声明:我们的研究引入了一种蒸发辅助接枝策略来制造堆叠聚合物簇涂层,克服了传统聚合物刷的不稳定性。这些涂层具有优异的防污性能,并支持功能组件的多功能集成。值得注意的是,由此产生的堆叠的模拟肝素聚合物涂层有效地诱导内皮网络的形成,与商业的基于matrigel的检测相媲美。通过利用精确工程的界面结构和分子相互作用,这种可扩展、低成本的方法为组织工程应用中的生物材料表面设计提供了一种解决方案。
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引用次数: 0
Metal-organic frameworks for CRISPR/Cas9 gene editing delivery: Innovations in therapeutic and diagnostic applications CRISPR/Cas9基因编辑传递的金属-有机框架:治疗和诊断应用的创新。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.030
Zhengxian Su , Zeyang Liang , Qiong Wu , Siwen Xu , Chengxin Li , Hanying Zheng , Chengxin Wu , Weizhi Ji , Yuyu Niu , Zebin Yang
CRISPR/Cas gene editing technology demonstrates significant promise in the treatment of various diseases, and a precise, efficient and safe delivery system is a key to realize gene therapy. Although traditional viral vectors can achieve superior transfection efficiency, viruses suffer from low reproduction efficiency and the risk of random gene integration, further limiting their wide application. Notably, metal-organic frameworks (MOFs), with tunable pore structure, easy surface chemical modification, good biocompatibility and physiological stability, have drawn much attention in the domain of targeted delivery of gene editing systems. Compared to lipid nanoparticles (LNPs) and extracellular vesicles (EVs), MOFs offer superior cargo loading (>80 % for proteins) and protect nucleic acids from degradation, while their stimuli-responsive degradation enables controlled release. This review focus on the cutting-edge advances of intelligent-responsive MOFs in delivering gene editing systems to against diseases, including endogenous responses (e.g., ATP, pH, redox microenvironment) and exogenous stimulus responses (e.g., photothermal, ultrasound) in the disease microenvironment, as well as systematically summarize the synergistic therapy of gene editing therapy combined with chemotherapy, chemodynamic therapy, photodynamic therapy, and sonodynamic therapy based on the delivery systems of MOFs. Additionally, we further summarize the research of MOFs-based CRISPR/Cas delivery system as a bio-probe for viral, nucleic acid and RNA examination. This study will help facilitate the clinical translation of MOFs-based CRISPR/Cas delivery systems in the field of therapy and detection of diseases.

Statement of significance

This article reviews the cutting-edge advances of intelligent-responsive MOFs in delivering CRISPR/Cas systems to against diseases, including endogenous responses (e.g., pH, ATP, redox microenvironment) and exogenous stimulus responses (e.g., photothermal, ultrasound) in the disease microenvironment, as well as systematically summarize the synergistic therapy of gene editing therapy combined with chemotherapy, chemodynamic therapy, photodynamic therapy, and sonodynamic therapy based on the delivery systems of MOFs. Importantly, the potential applications of MOFs-based CRISPR/Cas delivery system as a bio-probe for viral, nucleic acid and RNA examination also have been discussed. This study will provide insights for the development of MOFs-based CRISPR/Cas delivery systems in the therapy and detection of clinical diseases.
CRISPR/Cas基因编辑技术在多种疾病的治疗中显示出巨大的前景,而精准、高效、安全的递送系统是实现基因治疗的关键。传统的病毒载体虽然具有较高的转染效率,但病毒存在繁殖效率低和基因随机整合的风险,进一步限制了其广泛应用。值得一提的是,金属有机框架(MOFs)具有可调节的孔隙结构、易于表面化学修饰、良好的生物相容性和生理稳定性,在基因编辑系统靶向递送领域备受关注。与脂质纳米颗粒(LNPs)和细胞外囊泡(ev)相比,mof提供了更好的载货能力(蛋白质载货率为80%),并保护核酸免受降解,同时它们的刺激响应降解能够控制释放。本文综述了智能响应型mof在传递基因编辑系统对抗疾病方面的最新进展,包括疾病微环境中的内源性反应(如ATP、pH、氧化还原微环境)和外源性刺激反应(如光热、超声),并系统总结了基因编辑治疗与化疗、化疗动力治疗、光动力治疗、以及基于mof传送系统的声动力疗法。此外,我们进一步总结了基于mof的CRISPR/Cas传递系统作为病毒、核酸和RNA检测的生物探针的研究进展。本研究将有助于促进基于mofs的CRISPR/Cas传递系统在疾病治疗和检测领域的临床转化。意义陈述:本文综述了智能响应mof在传递CRISPR/Cas系统对抗疾病方面的前沿进展,包括疾病微环境中的内源性反应(如pH、ATP、氧化还原微环境)和外源性刺激反应(如光热、超声),并系统总结了基因编辑治疗与化疗、化疗动力治疗、光动力治疗、以及基于mof传送系统的声动力疗法。重要的是,本文还讨论了基于mof的CRISPR/Cas递送系统作为病毒、核酸和RNA检测的生物探针的潜在应用。该研究将为基于mofs的CRISPR/Cas传递系统在临床疾病治疗和检测中的发展提供见解。
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引用次数: 0
Polysaccharide-inspired biomaterials for skeletal muscle regeneration: innovations for volumetric muscle loss treatment 骨骼肌再生的多糖启发生物材料:体积肌肉损失治疗的创新。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.019
Yantong Li , Jianan Chen , Shuo Chen , Xue Ding , Xinfeng Zhou , Jin Li , Tingting Zhu , Yong Xu , Fan He
Volumetric muscle loss (VML) is a severe condition caused by extensive damage to muscle tissue that exceeds the body's intrinsic regenerative capacity, resulting in significant functional deficits and long-term disability. Current clinical treatments, including autologous muscle grafts and physical therapy, often fall short due to donor site morbidity, limited functional recovery, and an inability to fully restore muscle structure and function. Polysaccharides as natural macromolecules are characterized by inherent biocompatibility, degradability, and tunable mechanical properties, making them highly suitable for tissue engineering applications. This comprehensive review examines the innovative application of polysaccharide-based biomaterials in VML repair, emphasizing their translational potential to regenerative treatment outcomes. Polysaccharide-based biomaterials can significantly enhance muscle regeneration by providing structural support, modulating immune responses to minimize fibrosis, and promoting new vascular and nerve formation, which are essential for functional muscle recovery. More importantly, these materials serve as effective carriers for cell therapy and the delivery of bioactive molecules, thereby enhancing regenerative efficacy. Despite challenges such as standardizing preparation protocols, ensuring consistent biocompatibility, and optimizing degradation rates, polysaccharide-based biomaterials hold great promise for advancing skeletal muscle regeneration and offer a potential breakthrough in treating VML.

Statement of significance

Volumetric muscle loss (VML) is a severe clinical condition characterized by extensive muscle tissue damage that exceeds the body's natural regenerative capacity. Polysaccharide-based biomaterials have been extensively applied in tissue repair due to their favorable biological properties. They offer a promising therapeutic strategy for VML, for which currently available long-term treatments are limited in both safety and efficacy. However, a comprehensive review detailing the interaction mechanisms between polysaccharide-based biomaterials and muscle tissue regeneration remains lacking. This article focuses on the interactions and highlights recent evidence on the capacity of polysaccharide promoting myogenesis, modulating immune responses, restoring neural innervation, stimulating angiogenesis, and enhancing antioxidant activity. This review article provides insights into the future design and application of polysaccharide-based biomaterials for skeletal muscle regeneration after acute injuries.
体积性肌肉损失(VML)是一种严重的疾病,由肌肉组织的广泛损伤引起,超过了身体固有的再生能力,导致严重的功能缺陷和长期残疾。目前的临床治疗,包括自体肌肉移植和物理治疗,由于供体部位的发病率,有限的功能恢复,以及无法完全恢复肌肉结构和功能,往往达不到预期的效果。多糖作为天然大分子,具有固有的生物相容性、可降解性和可调节的力学性能,非常适合于组织工程应用。本文综述了基于多糖的生物材料在VML修复中的创新应用,强调了它们对再生治疗结果的转化潜力。基于多糖的生物材料可以通过提供结构支持,调节免疫反应以减少纤维化,促进新血管和神经的形成,从而显著增强肌肉再生,这对肌肉功能恢复至关重要。更重要的是,这些材料作为细胞治疗和生物活性分子递送的有效载体,从而提高再生功效。尽管存在标准化制备方案、确保一致的生物相容性和优化降解率等挑战,但基于多糖的生物材料在促进骨骼肌再生方面有着巨大的希望,并为治疗VML提供了潜在的突破。意义声明:体积性肌肉损失(VML)是一种严重的临床疾病,其特征是广泛的肌肉组织损伤超过了身体的自然再生能力。多糖基生物材料以其良好的生物学特性在组织修复中得到了广泛的应用。它们为VML提供了一个有希望的治疗策略,目前可用的长期治疗在安全性和有效性方面都是有限的。然而,多糖基生物材料与肌肉组织再生之间的相互作用机制的全面回顾仍然缺乏。本文重点介绍了多糖促进肌肉生成、调节免疫反应、恢复神经支配、刺激血管生成和增强抗氧化活性等方面的最新证据。本文综述了多糖基生物材料在急性损伤后骨骼肌再生中的应用前景。
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引用次数: 0
Next-generation supramolecular photosensitizers based on coordination-driven self-assembly for therapeutic applications 基于协同驱动自组装的下一代超分子光敏剂的治疗应用。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.039
Chonglu Li , Junhua Zhang , Qiao Song , Yuting Wang , Yanping Liu , Jingxin Wang , Yao Sun
Photosensitizers (PSs) that generate reactive oxygen species (ROS) under light irradiation are pivotal for biomedical applications owing to precise spatiotemporal control, negligible drug resistance, and minimal side effects. Yet conventional PSs often suffer from complex synthesis, low ROS quantum yields, and aggregation-induced ROS quenching. Coordination-driven self-assembly offers an efficient strategy to address these issues by combining metal acceptors with photosensitizing ligands to yield discrete, tunable supramolecular architectures. Heavy-atom effects from metal centers enhance intersystem crossing and ROS generation, while rigid, charged frameworks mitigate aggregation-caused ROS quenching and improve cellular or bacterial uptake. Incorporation of long-wavelength ligands further increases therapeutic penetration. These features enable broad applications in bioimaging, photodynamic therapy (PDT), chemotherapy, immunotherapy, and multimodal treatments. This review summarizes recent advances in the rational design of supramolecular PSs, covering fundamental principles, representative synthetic strategies, and state-of-the-art anticancer and antibacterial applications, including chemo–photodynamic combination therapy, photothermal–photodynamic dual therapy, and photoactivated immunotherapy. Remaining challenges and future opportunities are highlighted to guide the development of next-generation supramolecular PSs for clinical translation.

Statement of significance

Supramolecular photosensitizers (PSs) assembled via coordination-driven strategies offer a promising platform for light-mediated biomedical therapies. By integrating metal centers and photosensitizing ligands, these systems enhance ROS generation, suppress aggregation-caused quenching, and enable tunable architectures with improved biological performance. This review highlights recent progress in the design and therapeutic applications of supramolecular PSs, providing insights that may advance their clinical translation for cancer and antibacterial treatments.
光敏剂(ps)在光照射下产生活性氧(ROS),由于其精确的时空控制、可忽略的耐药性和最小的副作用,在生物医学应用中至关重要。然而,传统的ps通常存在合成复杂、ROS量子产率低以及聚集诱导的ROS猝灭等问题。协调驱动的自组装提供了一种有效的策略来解决这些问题,通过将金属受体与光敏配体结合,产生离散的、可调的超分子结构。来自金属中心的重原子效应增强了系统间的交叉和ROS的产生,而刚性的带电框架则减轻了聚集引起的ROS猝灭,并改善了细胞或细菌的摄取。长波配体的掺入进一步增加了治疗的穿透性。这些特点使生物成像、光动力治疗(PDT)、化疗、免疫治疗和多模式治疗得到广泛应用。本文综述了超分子ps合理设计的基本原理、代表性合成策略以及抗癌和抗菌应用的最新进展,包括化学-光动力联合治疗、光热-光动力双重治疗和光激活免疫治疗。强调了当前存在的挑战和未来的机遇,以指导下一代用于临床翻译的超分子ps的发展。意义声明:通过协调驱动策略组装的超分子光敏剂(ps)为光介导的生物医学治疗提供了一个有前途的平台。通过整合金属中心和光敏配体,这些系统增强了ROS的产生,抑制了聚集引起的猝灭,并使结构可调,提高了生物性能。本文综述了超分子ps的设计和治疗应用方面的最新进展,为其在癌症和抗菌治疗方面的临床应用提供了新的见解。
{"title":"Next-generation supramolecular photosensitizers based on coordination-driven self-assembly for therapeutic applications","authors":"Chonglu Li ,&nbsp;Junhua Zhang ,&nbsp;Qiao Song ,&nbsp;Yuting Wang ,&nbsp;Yanping Liu ,&nbsp;Jingxin Wang ,&nbsp;Yao Sun","doi":"10.1016/j.actbio.2025.12.039","DOIUrl":"10.1016/j.actbio.2025.12.039","url":null,"abstract":"<div><div>Photosensitizers (PSs) that generate reactive oxygen species (ROS) under light irradiation are pivotal for biomedical applications owing to precise spatiotemporal control, negligible drug resistance, and minimal side effects. Yet conventional PSs often suffer from complex synthesis, low ROS quantum yields, and aggregation-induced ROS quenching. Coordination-driven self-assembly offers an efficient strategy to address these issues by combining metal acceptors with photosensitizing ligands to yield discrete, tunable supramolecular architectures. Heavy-atom effects from metal centers enhance intersystem crossing and ROS generation, while rigid, charged frameworks mitigate aggregation-caused ROS quenching and improve cellular or bacterial uptake. Incorporation of long-wavelength ligands further increases therapeutic penetration. These features enable broad applications in bioimaging, photodynamic therapy (PDT), chemotherapy, immunotherapy, and multimodal treatments. This review summarizes recent advances in the rational design of supramolecular PSs, covering fundamental principles, representative synthetic strategies, and state-of-the-art anticancer and antibacterial applications, including chemo–photodynamic combination therapy, photothermal–photodynamic dual therapy, and photoactivated immunotherapy. Remaining challenges and future opportunities are highlighted to guide the development of next-generation supramolecular PSs for clinical translation.</div></div><div><h3>Statement of significance</h3><div>Supramolecular photosensitizers (PSs) assembled via coordination-driven strategies offer a promising platform for light-mediated biomedical therapies. By integrating metal centers and photosensitizing ligands, these systems enhance ROS generation, suppress aggregation-caused quenching, and enable tunable architectures with improved biological performance. This review highlights recent progress in the design and therapeutic applications of supramolecular PSs, providing insights that may advance their clinical translation for cancer and antibacterial treatments.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 549-569"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Ex-ovo cultured chorioallantois membrane as a biointerface platform for extended angiogenesis studies 卵外培养绒毛尿囊膜作为扩展血管生成研究的生物界面平台。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.006
Ahmed M. Abou-Shanab , Abdelrahman AlOkda
Angiogenesis modeling in a physiologically relevant, ethically acceptable, and versatile system remains a critical need in cancer biology, regenerative medicine, and preclinical drug testing. The chick chorioallantoic membrane (CAM) is a well-established model for studying angiogenesis, tumor growth, tissue grafting, and therapeutic responses; however, conventional in-ovo approaches are limited by a short experimental window (E7-E14.5), immune-related constraints, and restricted imaging accessibility. In this review, we critically assess the CAM current biomedical applications, including tumor angiogenesis and metastasis, biomaterial integration, immune-oncology modeling, and high-content drug screening. We present a temporal profiling of angiogenesis-associated genes during CAM development, revealing a coordinated sequence of pro-angiogenic, remodeling, and inhibitory phases, and identifying E10-E11 as the optimal harvest window for maximal sprouting and vascular responsiveness. To overcome in-ovo limitations, we propose and validate an ex-ovo cultured CAM model, surgically isolated from the embryo and maintained as a viable, vascularized scaffold. Proof-of-concept assays illustrate feasibility, including preserved endothelial integrity (CD31, CD34), metabolic activity (MTT), oxidative responses (DHR123), and nitric oxide secretion, supporting the conceptual framework developed in this review. With strong potential for standardization, this ex-ovo CAM system could bridge the gap between simple in-vitro assays and complex in-vivo models, enabling longer-term experimentation, precise spatial control, and compatibility with tumor organoids, immune cell co-cultures, and engineered tissues.

Statement of significance

The chick chorioallantoic membrane (CAM) is widely used to study angiogenesis and tumor biology, but its in ovo format is limited by a short experimental window and ethical constraints. This review introduces an ex-ovo cultured CAM system that preserves vascular and extracellular matrix integrity while extending experimental usability. By positioning the CAM as a biologically derived biointerface, we highlight its capacity to model biomaterial-cell interactions, vascular remodeling, and tissue integration. This platform provides a cost-effective, ethically refined, and translational tool that bridges in vitro assays and mammalian models, directly advancing biomaterials science and regenerative applications.
在一个生理学上相关的、伦理上可接受的、通用的系统中建立血管生成模型仍然是癌症生物学、再生医学和临床前药物测试的关键需求。鸡毛囊尿囊膜(CAM)是研究血管生成、肿瘤生长、组织移植和治疗反应的良好模型;然而,传统的卵内入路受到实验窗口短(E7-E14.5)、免疫相关约束和受限的成像可及性的限制。在这篇综述中,我们批判性地评估了CAM目前在生物医学上的应用,包括肿瘤血管生成和转移、生物材料整合、免疫肿瘤学建模和高含量药物筛选。我们展示了CAM发育过程中血管生成相关基因的时间谱,揭示了促血管生成、重塑和抑制阶段的协调序列,并确定E10-E11是最大发芽和血管反应的最佳收获窗口。为了克服卵内限制,我们提出并验证了一种卵外培养的CAM模型,通过手术从胚胎中分离出来,并作为一个有活力的血管化支架维持。概念验证分析证明了可行性,包括保存的内皮完整性(CD31, CD34),代谢活性(MTT),氧化反应(DHR123)和一氧化氮分泌,支持本综述中建立的概念框架。该系统具有强大的标准化潜力,可以弥合简单的体外分析和复杂的体内模型之间的差距,实现长期实验,精确的空间控制,以及与肿瘤类器官,免疫细胞共培养和工程组织的兼容性。意义声明:鸡绒毛膜(chorioallantoic membrane, CAM)被广泛用于血管生成和肿瘤生物学的研究,但其卵状结构受到实验窗口短和伦理约束的限制。本文介绍了一种体外培养CAM系统,该系统在保持血管和细胞外基质完整性的同时扩大了实验的可用性。通过将CAM定位为生物来源的生物界面,我们强调了其模拟生物材料-细胞相互作用、血管重塑和组织整合的能力。该平台提供了一种成本效益高、道德规范的转化工具,连接了体外分析和哺乳动物模型,直接推进了生物材料科学和再生应用。
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引用次数: 0
A physiological oxygen gradient liver-zonation-on-a-chip reveals HIF-2α intervention in hepatic lipotoxicity 一项生理性氧梯度肝脏分区芯片揭示HIF-2α干预肝脂毒性。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.11.044
Yushen Wang , Xinyu Li , Junlei Han , Feng Kong , Zhipeng Xu , Huili Hu , Li Wang
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disease characterized by lipid zonation, which is closely linked to the functional zonation of liver lobules. However, existing models cannot faithfully replicate the oxygen gradient that regulates liver zonation, hindering a clear understanding of the progression and intervention mechanisms in MASLD. Here, we constructed a MASLD liver-zonation-on-a-chip that utilizes an engineering strategy based on “environmental oxygen convection and diffusion”, achieving a controllable oxygen concentration gradient (3.7 %-8.9 %) that closely mimics the in vivo hepatic microenvironment. This platform successfully recapitulates the typical features and clinicopathological phenotypes of the liver lobule while enabling continuous monitoring of liver injury. We found that upregulation of the oxygen-sensing factor HIF-2α does not directly promote lipid accumulation. Instead, it indirectly facilitates the progression of MASLD by enhancing the transcriptional activity of β-catenin through the WNT signaling pathway (e.g., AXIN2, DVL1). As regulators of the damage process, HIF-2α and β-catenin may be targeted to improve outcomes in MASLD.

Statement of Significance

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common liver disorder characterized by lipid zonation, which is closely related to the functional zonation of liver lobules. However, existing models are unable to accurately replicate the oxygen (O2) gradients that regulate liver zonation, a limitation that hinders their ability to accurately reflect hepatocyte pathophysiology and obstructs understanding of the mechanisms underlying MASLD progression. This study constructs a liver-zonation-on-a-chip with a controllable physiological O₂ gradient and integrated biosensing for non-destructive injury monitoring. The O2 gradient chip successfully replicates liver lobule zonation, providing an engineering approach to overcoming the challenge of low regional heterogeneity in liver organoids. The application of the liver-zonation-on-a-chip in pathological assessments has also been thoroughly evaluated, offering potential solutions for MASLD interventions.
代谢功能障碍相关脂肪变性肝病(MASLD)是一种以脂质分区为特征的常见肝脏疾病,与肝小叶的功能分区密切相关。然而,现有的模型不能忠实地复制调节肝脏分区的氧梯度,阻碍了对MASLD进展和干预机制的清晰理解。在这里,我们构建了一个基于“环境氧对流和扩散”的工程策略的MASLD肝脏分区芯片,实现了一个可控的氧浓度梯度(3.7%-8.9%),接近模拟体内肝脏微环境。该平台成功地概括了肝小叶的典型特征和临床病理表型,同时能够连续监测肝损伤。我们发现,氧敏感因子HIF-2α的上调并不直接促进脂质积累。相反,它通过WNT信号通路(如AXIN2、DVL1)增强β-catenin的转录活性,间接促进MASLD的进展。作为损伤过程的调节因子,HIF-2α和β-catenin可以靶向改善MASLD的预后。声明意义:代谢功能障碍相关脂肪变性肝病(MASLD)是一种以脂质分带为特征的常见肝脏疾病,与肝小叶的功能分带密切相关。然而,现有的模型无法准确地复制调节肝脏分区的氧(O2)梯度,这一限制阻碍了它们准确反映肝细胞病理生理的能力,并阻碍了对MASLD进展机制的理解。本研究构建了一种具有可控生理O₂梯度和集成生物传感的肝脏分区芯片,用于非破坏性损伤监测。O2梯度芯片成功复制肝小叶分区,为克服肝类器官低区域异质性的挑战提供了一种工程方法。肝脏芯片分区在病理评估中的应用也得到了全面的评估,为MASLD干预提供了潜在的解决方案。
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引用次数: 0
A latent TGF-β conjugated scaffold improves neocartilage development 潜在TGF-β共轭支架促进新软骨发育。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.11.037
Tianbai Wang , Yifan Peng , Bor-Lin Huang , Enkhjargal Budbazar , Celina C. Maldonado , Andrew Martin , Matthew D. Layne , Joanne E. Murphy-Ullrich , Mark W. Grinstaff , Michael B. Albro
TGF-β is conventionally supplemented in culture medium at supraphysiologic doses to accelerate neocartilage development. While enhancing extracellular matrix (ECM) biosynthesis, supraphysiologic TGF-β further promotes non-hyaline cartilage features, including hyperplasia, hypertrophy, and ECM heterogeneities. In native cartilage, TGF-β is present in a latent complex (LTGF-β), which undergoes cell-mediated activation, leading to moderated, physiologic dosing regimens that avoid detrimental features associated with TGF-β excesses. Here, we explore a bio-inspired strategy, consisting of LTGF-β-conjugated scaffolds, providing TGF-β exposure regimens that are moderated and uniformly administered throughout the construct. We evaluate the performance of LTGF-β scaffolds with bovine chondrocyte-seeded agarose constructs compared to outcomes from active TGF-β media supplementation (MS) at a physiologic 0.3 ng/mL dose (MS-0.3), supraphysiologic 10 ng/mL dose (MS-10), or TGF-β free. LTGF-β scaffolds achieve native-matched mechanical properties and sGAG content, while providing a cell morphology and collagen distribution more reminiscent of hyaline cartilage. LTGF-β scaffolds further afford an optimal chondrogenic phenotype, marked by an up to 28-fold reduction of COL-I and 17-fold reduction of COL-X expression relative to TGF-β-free and MS-10, respectively. Further, LTGF-β scaffolds significantly reduce mechanical and biochemical heterogeneities relative to MS-0.3 and MS-10. Overall, LTGF-β scaffolds improve the composition, structure, material properties, and cell phenotype of neocartilage.

Statement of significance

Inspired by native regulatory mechanisms, we introduce a latent TGF-β conjugated scaffold that enables localized, cell-mediated activation of TGF-β at physiologic levels. This approach yields neocartilage with native-matched composition and mechanical properties, while maintaining a hyaline-cartilage-like cell phenotype and morphology, thus mitigating the adverse developmental features associated with conventional active TGF-β dosing. This bio-inspired platform offers a compelling solution to current TGF-β delivery challenges to improve cartilage regeneration outcomes.
TGF-β通常在培养基中以超生理剂量补充,以加速新软骨的发育。在增强细胞外基质(ECM)生物合成的同时,生理上TGF-β进一步促进非透明软骨特征,包括增生、肥大和ECM异质性。在天然软骨中,TGF-β存在于一种潜伏复合物(LTGF-β)中,LTGF-β经历细胞介导的激活,导致适度的生理性给药方案,避免与TGF-β过量相关的有害特征。在这里,我们探索了一种生物启发策略,包括LTGF-β缀合支架,提供TGF-β暴露方案,在整个构建过程中被调节和统一施用。我们评估了用牛软骨细胞种子琼脂糖构建的LTGF-β支架的性能,并将其与活性TGF-β培养基补充(MS)在生理剂量0.3 ng/mL (MS-0.3)、超生理剂量10 ng/mL (MS-10)或TGF-β游离剂量的结果进行了比较。对于缩小尺寸的结构,LTGF-β支架实现天然匹配的机械性能和sGAG含量,同时提供更让人想起透明软骨的细胞形态和胶原分布。LTGF-β支架进一步提供了最佳的软骨形成表型,与TGF-β无支架和MS-10支架相比,COL-I和COL-X的表达分别减少了28倍和17倍。此外,对于常规大小的结构,LTGF-β支架相对于MS-0.3和MS-10显著降低了机械和生化异质性。总之,LTGF-β支架改善了新软骨的组成、结构、材料性能和细胞表型。意义声明:受天然调节机制的启发,我们引入了一种潜在的TGF-β共轭支架,可以在生理水平上实现局部的、细胞介导的TGF-β激活。这种方法产生的新软骨具有天然匹配的成分和机械性能,同时保持透明软骨样细胞表型和形态,从而减轻与传统活性TGF-β剂量相关的不良发育特征。这种生物启发的平台为当前TGF-β递送挑战提供了令人信服的解决方案,以改善软骨再生结果。
{"title":"A latent TGF-β conjugated scaffold improves neocartilage development","authors":"Tianbai Wang ,&nbsp;Yifan Peng ,&nbsp;Bor-Lin Huang ,&nbsp;Enkhjargal Budbazar ,&nbsp;Celina C. Maldonado ,&nbsp;Andrew Martin ,&nbsp;Matthew D. Layne ,&nbsp;Joanne E. Murphy-Ullrich ,&nbsp;Mark W. Grinstaff ,&nbsp;Michael B. Albro","doi":"10.1016/j.actbio.2025.11.037","DOIUrl":"10.1016/j.actbio.2025.11.037","url":null,"abstract":"<div><div>TGF-β is conventionally supplemented in culture medium at supraphysiologic doses to accelerate neocartilage development. While enhancing extracellular matrix (ECM) biosynthesis, supraphysiologic TGF-β further promotes non-hyaline cartilage features, including hyperplasia, hypertrophy, and ECM heterogeneities. In native cartilage, TGF-β is present in a latent complex (LTGF-β), which undergoes cell-mediated activation, leading to moderated, physiologic dosing regimens that avoid detrimental features associated with TGF-β excesses. Here, we explore a bio-inspired strategy, consisting of LTGF-β-conjugated scaffolds, providing TGF-β exposure regimens that are moderated and uniformly administered throughout the construct. We evaluate the performance of LTGF-β scaffolds with bovine chondrocyte-seeded agarose constructs compared to outcomes from active TGF-β media supplementation (MS) at a physiologic 0.3 ng/mL dose (MS-0.3), supraphysiologic 10 ng/mL dose (MS-10), or TGF-β free. LTGF-β scaffolds achieve native-matched mechanical properties and sGAG content, while providing a cell morphology and collagen distribution more reminiscent of hyaline cartilage. LTGF-β scaffolds further afford an optimal chondrogenic phenotype, marked by an up to 28-fold reduction of COL-I and 17-fold reduction of COL-X expression relative to TGF-β-free and MS-10, respectively. Further, LTGF-β scaffolds significantly reduce mechanical and biochemical heterogeneities relative to MS-0.3 and MS-10. Overall, LTGF-β scaffolds improve the composition, structure, material properties, and cell phenotype of neocartilage.</div></div><div><h3>Statement of significance</h3><div>Inspired by native regulatory mechanisms, we introduce a latent TGF-β conjugated scaffold that enables localized, cell-mediated activation of TGF-β at physiologic levels. This approach yields neocartilage with native-matched composition and mechanical properties, while maintaining a hyaline-cartilage-like cell phenotype and morphology, thus mitigating the adverse developmental features associated with conventional active TGF-β dosing. This bio-inspired platform offers a compelling solution to current TGF-β delivery challenges to improve cartilage regeneration outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 145-159"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Calcification and structural damage together accelerate porcine pericardium failure 钙化和结构损伤共同加速猪心包衰竭。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.11.046
Luke Guerin , Alix Whelan , Jack O’Leary , Jessica Bagnall , David O’Reilly , Rachel Burke , Evelyn Campbell , Celia Hughes , Emily Growney , Caitríona Lally
Aortic stenosis (AS) is characterised by the narrowing and stiffening of the aortic valve, which restricts blood flow from the heart to the rest of the body. Severe AS is a life-threatening condition which affects 1.48 % of individuals aged 55 and older, with a four-year mortality rate of 44.9 % if left untreated. Minimally invasive treatment for AS involves the implantation of a bioprosthetic valve with porcine or bovine pericardium leaflets, which frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage. The relationship between these two durability-limiting processes is debated, and the influence of device crimping on both factors is not comprehensively understood. This study aims to explore the relationship between calcification and structural damage and determine if device crimping affects these processes. First, porcine pericardium (PP) tissue was exposed to either in vitro calcification in unloaded conditions (calcification) or cyclic bulge loading in saline, without calcification (structural damage). Subsequently, PP was simultaneously calcified and cyclically loaded for 30 million cycles. Simultaneous calcification and loading led to dramatically increased calcification and structural damage, including tissue rupture. Device crimping was not found to have a significant impact on calcification or structural damage. However, fibre architecture was found to affect rupture location, and dramatically affect the rate of rupture of PP. This finding has implications for future bioprosthetic valve leaflet anti-calcification strategies, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification.

Statement of significance

Porcine pericardium (PP) is a commonly used biomaterial, most frequently in the leaflets of bioprosthetic valves. These devices frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage of their leaflets. This work shows that calcification and structural damage work together to accelerate failure of PP, with dramatically increased calcification and structural damage of PP, including rupture, when the tissue is exposed to both simultaneously. Fibre architecture of PP was found to affect rupture location, and dramatically affect rate of rupture. This finding has implications for bioprosthetic leaflet durability, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification and maximise valve durability.
主动脉瓣狭窄(AS)的特征是主动脉瓣变窄和僵硬,这限制了血液从心脏流向身体其他部位。严重AS是一种危及生命的疾病,55岁及以上的患者中有1.48%受到影响,如果不及时治疗,四年死亡率为44.9%。AS的微创治疗包括植入带有猪或牛心包小叶的生物假瓣膜,由于部分由钙化和结构损伤引起的反流或狭窄而经常失败。这两个耐久性限制过程之间的关系是有争议的,并且器件卷曲对这两个因素的影响还没有全面了解。本研究旨在探讨钙化和结构损伤之间的关系,并确定设备卷曲是否影响这些过程。首先,将猪心包(PP)组织暴露在无负荷条件下体外钙化(钙化)或生理盐水中循环膨化(无钙化)。随后,PP同时钙化并循环加载3000万次。同时钙化和负荷导致钙化和结构损伤急剧增加,包括组织破裂。没有发现设备卷曲对钙化或结构损伤有显著影响。然而,研究发现纤维结构会影响破裂位置,并显著影响PP的破裂率。这一发现对未来的生物假体瓣膜小叶抗钙化策略具有重要意义,其中应考虑受潜在组织纤维结构影响的组织力学,以尽量减少结构损伤和钙化。意义说明:猪心包(PP)是一种常用的生物材料,最常用于生物假体瓣膜的小叶。这些装置经常因反流或狭窄而失效,部分原因是其小叶的钙化和结构损伤。这项工作表明,钙化和结构损伤共同作用加速PP的失效,当组织同时暴露于两者时,PP的钙化和结构损伤(包括破裂)急剧增加。聚丙烯的纤维结构影响断裂位置,并显著影响断裂率。这一发现对生物假体小叶耐久性具有重要意义,其中应考虑受底层组织纤维结构影响的组织力学,以最大限度地减少结构损伤和钙化,并最大限度地提高瓣膜耐久性。
{"title":"Calcification and structural damage together accelerate porcine pericardium failure","authors":"Luke Guerin ,&nbsp;Alix Whelan ,&nbsp;Jack O’Leary ,&nbsp;Jessica Bagnall ,&nbsp;David O’Reilly ,&nbsp;Rachel Burke ,&nbsp;Evelyn Campbell ,&nbsp;Celia Hughes ,&nbsp;Emily Growney ,&nbsp;Caitríona Lally","doi":"10.1016/j.actbio.2025.11.046","DOIUrl":"10.1016/j.actbio.2025.11.046","url":null,"abstract":"<div><div>Aortic stenosis (AS) is characterised by the narrowing and stiffening of the aortic valve, which restricts blood flow from the heart to the rest of the body. Severe AS is a life-threatening condition which affects 1.48 % of individuals aged 55 and older, with a four-year mortality rate of 44.9 % if left untreated. Minimally invasive treatment for AS involves the implantation of a bioprosthetic valve with porcine or bovine pericardium leaflets, which frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage. The relationship between these two durability-limiting processes is debated, and the influence of device crimping on both factors is not comprehensively understood. This study aims to explore the relationship between calcification and structural damage and determine if device crimping affects these processes. First, porcine pericardium (PP) tissue was exposed to either in vitro calcification in unloaded conditions (calcification) or cyclic bulge loading in saline, without calcification (structural damage). Subsequently, PP was simultaneously calcified and cyclically loaded for 30 million cycles. Simultaneous calcification and loading led to dramatically increased calcification and structural damage, including tissue rupture. Device crimping was not found to have a significant impact on calcification or structural damage. However, fibre architecture was found to affect rupture location, and dramatically affect the rate of rupture of PP. This finding has implications for future bioprosthetic valve leaflet anti-calcification strategies, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification.</div></div><div><h3>Statement of significance</h3><div>Porcine pericardium (PP) is a commonly used biomaterial, most frequently in the leaflets of bioprosthetic valves. These devices frequently succumb to failure due to regurgitation or stenosis caused in part by calcification and structural damage of their leaflets. This work shows that calcification and structural damage work together to accelerate failure of PP, with dramatically increased calcification and structural damage of PP, including rupture, when the tissue is exposed to both simultaneously. Fibre architecture of PP was found to affect rupture location, and dramatically affect rate of rupture. This finding has implications for bioprosthetic leaflet durability, where tissue mechanics influenced by the underlying tissue fibre architecture should be considered to minimise both structural damage and calcification and maximise valve durability.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 82-94"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Engineered extracellular vesicles as multifunctional therapeutics for restoring periodontal homeostasis 工程细胞外囊泡作为修复牙周稳态的多功能疗法。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.11.060
Junjie Shi , Zongshuai Liu , Jirong Xie , Ze Zhao , Xin Huang , Zhengguo Cao
Periodontal homeostasis refers to the dynamic equilibrium between host defense, microbial control, and tissue remodeling in periodontal tissues. Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues, in which periodontal homeostasis is disturbed. Although many strategies have been developed, treatment of periodontitis and restoration of periodontal homeostasis remain challenging. Extracellular vesicles (EVs) have emerged as a potential cell-free platform for therapeutic applications due to their intrinsic capacity for intercellular communication and biocompatibility. With the advances in engineering, EVs can be functionally tailored to exhibit improved stability, targeting, and bioactivity, attracting increasing attention as regulators for periodontal homeostasis. Accumulating evidence indicates that engineered EVs exert diverse regulatory effects in the periodontal microenvironment, including anti-bacterial activity, anti-inflammatory properties, immunomodulation, antioxidant protection, regulation of programmed cell fate, and promotion of regeneration. Such multifunctional properties enable engineered EVs to address periodontal dysregulation and contribute to the stabilization of tissue homeostasis. This review highlights recent advances in the application of engineered EVs in periodontal research, summarizes their emerging therapeutic roles across these biological domains, and emphasizes their potential as versatile modulators for the maintenance and restoration of periodontal homeostasis.

Statement of significance

This review uniquely integrates recent progress in engineering extracellular vesicles (EVs) with biomaterial-based strategies to restore periodontal homeostasis, a perspective not comprehensively addressed in existing literature. By systematically analyzing approaches such as cargo and surface modification, scaffold incorporation, and artificial vesicle design, it highlights how engineered EVs overcome the limitations of native vesicles and achieve multifunctional regulation of microbial, immune, and regenerative processes. This work provides insights into the convergence of materials science, nanotechnology, and oral biology, and outlines future directions for translating engineered EVs into next-generation therapeutic platforms with broad relevance for biomaterial innovation and regenerative medicine.
牙周内稳态是指牙周组织中宿主防御、微生物控制和组织重塑之间的动态平衡。牙周炎是一种慢性炎症性疾病,其特征是牙周组织被破坏,牙周内平衡被扰乱。尽管已经开发了许多策略,但牙周炎的治疗和牙周稳态的恢复仍然具有挑战性。细胞外囊泡(EVs)由于其内在的细胞间通讯能力和生物相容性,已成为潜在的无细胞治疗应用平台。随着工程技术的进步,电动汽车可以在功能上进行定制,以表现出更好的稳定性、靶向性和生物活性,作为牙周稳态的调节剂越来越受到关注。越来越多的证据表明,工程ev对牙周微环境具有多种调节作用,包括抗菌活性、抗炎特性、免疫调节、抗氧化保护、程序性细胞命运调节和促进再生。这种多功能特性使工程ev能够解决牙周失调并有助于组织稳态的稳定。本文综述了工程化ev在牙周研究中的最新进展,总结了它们在这些生物学领域的新治疗作用,并强调了它们作为维持和恢复牙周稳态的多功能调节剂的潜力。意义声明:本综述独特地整合了工程细胞外囊泡(ev)与基于生物材料的策略来恢复牙周稳态的最新进展,这一观点在现有文献中尚未全面解决。通过系统分析货物和表面修饰、支架结合和人工囊泡设计等方法,重点介绍了工程电动汽车如何克服天然囊泡的局限性,实现微生物、免疫和再生过程的多功能调节。这项工作为材料科学、纳米技术和口腔生物学的融合提供了见解,并概述了将工程电动汽车转化为下一代治疗平台的未来方向,这些平台与生物材料创新和再生医学具有广泛的相关性。
{"title":"Engineered extracellular vesicles as multifunctional therapeutics for restoring periodontal homeostasis","authors":"Junjie Shi ,&nbsp;Zongshuai Liu ,&nbsp;Jirong Xie ,&nbsp;Ze Zhao ,&nbsp;Xin Huang ,&nbsp;Zhengguo Cao","doi":"10.1016/j.actbio.2025.11.060","DOIUrl":"10.1016/j.actbio.2025.11.060","url":null,"abstract":"<div><div>Periodontal homeostasis refers to the dynamic equilibrium between host defense, microbial control, and tissue remodeling in periodontal tissues. Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues, in which periodontal homeostasis is disturbed. Although many strategies have been developed, treatment of periodontitis and restoration of periodontal homeostasis remain challenging. Extracellular vesicles (EVs) have emerged as a potential cell-free platform for therapeutic applications due to their intrinsic capacity for intercellular communication and biocompatibility. With the advances in engineering, EVs can be functionally tailored to exhibit improved stability, targeting, and bioactivity, attracting increasing attention as regulators for periodontal homeostasis. Accumulating evidence indicates that engineered EVs exert diverse regulatory effects in the periodontal microenvironment, including anti-bacterial activity, anti-inflammatory properties, immunomodulation, antioxidant protection, regulation of programmed cell fate, and promotion of regeneration. Such multifunctional properties enable engineered EVs to address periodontal dysregulation and contribute to the stabilization of tissue homeostasis. This review highlights recent advances in the application of engineered EVs in periodontal research, summarizes their emerging therapeutic roles across these biological domains, and emphasizes their potential as versatile modulators for the maintenance and restoration of periodontal homeostasis.</div></div><div><h3>Statement of significance</h3><div>This review uniquely integrates recent progress in engineering extracellular vesicles (EVs) with biomaterial-based strategies to restore periodontal homeostasis, a perspective not comprehensively addressed in existing literature. By systematically analyzing approaches such as cargo and surface modification, scaffold incorporation, and artificial vesicle design, it highlights how engineered EVs overcome the limitations of native vesicles and achieve multifunctional regulation of microbial, immune, and regenerative processes. This work provides insights into the convergence of materials science, nanotechnology, and oral biology, and outlines future directions for translating engineered EVs into next-generation therapeutic platforms with broad relevance for biomaterial innovation and regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"210 ","pages":"Pages 457-480"},"PeriodicalIF":9.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
In vitro silicone oil emulsification in retinal detachment treatment: Methods, designs, and future strategies 体外硅油乳化治疗视网膜脱离:方法、设计和未来策略。
IF 9.6 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-01 DOI: 10.1016/j.actbio.2025.12.024
Natalie Jaklová, Barbora Kamenická
<div><div>Silicone oils are widely used as intraocular tamponade agents in vitreoretinal surgery, particularly in the treatment of complex retinal detachments and other severe posterior segment pathologies such as proliferative diabetic retinopathy, macular holes, ocular trauma, or endophthalmitis. While they offer mechanical support for retinal reattachment, their prolonged intraocular presence is associated with the risk of emulsification, i.e., a process in which the oil phase breaks into subvisible droplets that can obstruct aqueous outflow and compromise visual outcomes. Although emulsification is frequently attributed to interfacial shear stresses generated during ocular motion, especially saccades, the underlying mechanisms remain poorly understood due to the multifactorial nature of the intraocular environment. This review provides a comprehensive analysis of experimental approaches used to investigate silicone oil emulsification, including vortex systems, mechanical shakers, artificial eye chambers, and microfluidic eye-on-a-chip platforms. We critically evaluate the physicochemical and biomechanical parameters influencing droplet formation. Despite significant progress, data from current in vitro models remain heterogeneous and often difficult to compare due to differences in design, fluid composition, and analytical endpoints. Based on the collective evidence, we propose a set of experimental recommendations aimed at emulsification in vitro, including the use of high-molecular-weight modified oils, standardized fluid compositions, advanced eye-mimicking platforms, and improved experimental and analytical protocols. Finally, we highlight the potential of next-generation testing platforms and biocompatible tamponades to offer physiologically relevant, reproducible, and standardized assessment of emulsification resistance. These insights aim to guide the rational design of improved tamponade agents and testing methodologies in future vitreoretinal applications.</div></div><div><h3>Statement of significance</h3><div>Silicone oils are widely used as tamponades in retinal detachment surgery, yet their long-term stability is compromised by emulsification, leading to severe complications such as glaucoma. Although many in vitro studies have attempted to model this process, their findings remain fragmented and often contradictory. This review provides the first systematic, cross-platform analysis of silicone oil emulsification, critically comparing mechanical, chamber-based, and eye-on-a-chip approaches. By identifying unifying trends, methodological gaps, and underexplored parameters such as interfacial rheology and biomechanics, it establishes a roadmap toward standardized, physiologically relevant testing. These insights are significant not only for improving current tamponade materials but also for guiding the design of next-generation biomaterials and experimental platforms at the interface of ophthalmology, biomaterials science, and fluid
硅油在玻璃体视网膜手术中被广泛用作眼内填塞剂,特别是在治疗复杂的视网膜脱离和其他严重的后段病变,如增殖性糖尿病视网膜病变、黄斑孔、眼外伤或眼内炎。虽然它们为视网膜重新附着提供了机械支持,但它们在眼内的长期存在与乳化的风险有关,即油相破裂成不可见的液滴的过程,可以阻碍水流出并影响视力。尽管乳化症经常被认为是由眼内运动(尤其是扫视)过程中产生的界面剪切应力引起的,但由于眼内环境的多因素性质,人们对其潜在机制知之甚少。本文综述了用于研究硅油乳化的实验方法,包括涡旋系统、机械振动器、人工眼室和微流控眼芯片平台。我们批判性地评估影响液滴形成的物理化学和生物力学参数。尽管取得了重大进展,但由于设计、流体成分和分析终点的差异,目前体外模型的数据仍然不均匀,往往难以比较。基于这些证据,我们提出了一套针对体外乳化的实验建议,包括使用高分子量改性油、标准化液体成分、先进的眼模拟平台以及改进的实验和分析方案。最后,我们强调了下一代测试平台和生物相容性填塞的潜力,以提供生理学上相关的、可重复的和标准化的乳化抗性评估。这些见解旨在指导在未来玻璃体视网膜应用中合理设计改进的填塞剂和测试方法。意义声明:硅油在视网膜脱离手术中被广泛用作填塞剂,但其长期稳定性受到乳化的影响,导致严重的并发症,如青光眼。尽管许多体外研究试图模拟这一过程,但他们的发现仍然是零散的,而且往往是相互矛盾的。这篇综述提供了第一个系统的、跨平台的硅油乳化分析,批判性地比较了机械的、基于腔室的和眼上芯片的方法。通过确定统一的趋势、方法上的差距和未充分开发的参数,如界面流变学和生物力学,它建立了标准化的路线图,生理学相关的测试。这些见解不仅对改善现有填塞材料具有重要意义,而且对指导下一代生物材料和实验平台的设计具有重要意义,这些实验平台位于眼科、生物材料科学和流体力学的界面。
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