Materials Science & Engineering C-Materials for Biological Applications最新文献_第10页

3D-bioprinted dual-crosslinked oxidized gellan gum-decellularized human amniotic membrane hydrogels reinforced with aminolyzed electrospun nanofibers for cartilage regeneration 生物3d打印双交联氧化结冷胶-脱细胞人羊膜水凝胶，氨基水解电纺丝纳米纤维增强软骨再生

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-16 DOI: 10.1016/j.bioadv.2025.214654

Fariba Hashemi-Afzal , Fatemeh Bagheri , Ebrahim Vasheghani-Farahani , Mahmoud Azami , Lobat Tayebi , Mohamadreza Baghaban Eslaminejad

Articular cartilage has limited self-healing capacity, driving the need for biomaterial scaffolds that replicate its hierarchical architecture and mechanical resilience. In this study, we present a dual-crosslinked hydrogel system for 3D bioprinting, composed of gellan gum (GG), oxidized GG (OGG), decellularized human amniotic membrane (dHAM), and aminolyzed polycaprolactone nanofibers (A-PCL NFs). Schiff base linkages between OGG aldehydes and amine groups in dHAM/A-PCL NFs, combined with Ca²⁺-mediated ionic gelation, provided a reinforced hydrogel network with tunable physicochemical properties. The resulting scaffolds exhibited high structural fidelity, a compressive modulus of 232.6 kPa, controlled swelling, and sustained degradation (30 % mass loss over 21 days). The integration of A-PCL NFs significantly enhanced mechanical performance and stabilized the hydrogel matrix, while dHAM supplied native extracellular matrix (ECM) cues. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) encapsulated in the bioink showed >85 % viability after 7 days and underwent robust chondrogenic differentiation, as confirmed by histology and increased glycosaminoglycan deposition. This biomimetic design—combining dynamic crosslinking, ECM-derived bioactivity, and NF reinforcement—demonstrates how structural and biochemical synergies can be harnessed to advance functional cartilage scaffolds. The platform shows strong potential for translational application in articular cartilage repair and may be extended to other load-bearing tissues requiring both mechanical integrity and biological functionality.

关节软骨的自我修复能力有限，因此需要复制其分层结构和机械弹性的生物材料支架。在这项研究中，我们提出了一种用于生物3D打印的双交联水凝胶体系，该体系由结冷胶（GG）、氧化GG （OGG）、脱细胞人羊膜（dHAM）和氨基化聚己内酯纳米纤维（a - pcl NFs）组成。在dHAM/ a - pcl NFs中，OGG醛和胺基之间的希夫碱键与Ca2+介导的离子凝胶结合，提供了一个具有可调物理化学性质的增强水凝胶网络。所得支架具有较高的结构保真度，压缩模量为232.6 kPa，可控制膨胀，持续降解（21天内质量损失30%）。A-PCL NFs的整合显著提高了机械性能并稳定了水凝胶基质，而dHAM提供了天然细胞外基质（ECM）线索。大鼠骨髓间充质干细胞（rBMSCs）被包裹在生物链接中，7天后显示出85%的存活率，并经历了强大的软骨分化，组织学和糖胺聚糖沉积的增加证实了这一点。这种仿生设计结合了动态交联、ecm衍生的生物活性和NF增强，展示了如何利用结构和生化协同作用来推进功能性软骨支架。该平台在关节软骨修复方面显示出强大的转化应用潜力，并可能扩展到需要机械完整性和生物功能的其他承重组织。

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引用次数: 0

Nanomaterial-based strategies to modulate macrophage polarization in osteoarthritis: A systematic review 基于纳米材料的策略来调节骨关节炎中的巨噬细胞极化：一项系统综述。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-15 DOI: 10.1016/j.bioadv.2025.214662

Giorgia Codispoti , Luca Cavazza , Melania Carniato , Gabriele Bilancia , Gianluca Giavaresi , Matilde Tschon

Osteoarthritis (OA) is a chronic degenerative joint disease characterised by progressive functional impairment due to erosion of the articular cartilage, remodelling of the subchondral bone and inflammation of the synovial tissue. In addition to mechanical and metabolic alterations, there is increasing evidence highlighting the pivotal role of macrophages in OA pathophysiology. The imbalance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes drives joint inflammation, extracellular matrix degradation, chondrocyte apoptosis and impaired tissue repair. Therefore, modulating macrophage polarization appears to be an attractive therapeutic target for preventing OA progression. In recent years, nanomaterials have emerged as an innovative approach to tackling this challenge. Their tunable size, morphology, and surface properties enable both direct immunomodulation and the delivery of therapeutic agents. This systematic review examined preclinical studies published between 2021 and 2025 that investigated the potential of various developed nanomaterials to polarize macrophages towards the M2 phenotype, thereby reducing joint inflammation and promoting cartilage protection and repair. Consistent results from both in vitro and in vivo included studies demonstrated their ability to reduce pro-inflammatory mediators related to M1-type macrophages while enhancing the expression of anti-inflammatory ones linked to M2-type macrophages, despite their differences in physicochemical properties. This suggested that nanomaterials could reprogram macrophages to suppress the inflammatory microenvironment of OA and slow down disease progression by lowering synovitis and cartilage damage. By influencing macrophage polarization and fostering a regenerative environment, nanotechnology may pave the way for more effective, targeted strategies in OA management.

骨关节炎（OA）是一种慢性退行性关节疾病，其特征是由于关节软骨的侵蚀、软骨下骨的重塑和滑膜组织的炎症导致的进行性功能损伤。除了机械和代谢改变，越来越多的证据强调巨噬细胞在OA病理生理中的关键作用。促炎M1和抗炎M2表型之间的不平衡驱动关节炎症、细胞外基质降解、软骨细胞凋亡和组织修复受损。因此，调节巨噬细胞极化似乎是预防OA进展的一个有吸引力的治疗靶点。近年来，纳米材料已经成为解决这一挑战的一种创新方法。它们可调节的大小、形态和表面特性使其既能进行直接免疫调节，又能递送治疗剂。本系统综述分析了2021年至2025年间发表的临床前研究，这些研究调查了各种开发的纳米材料使巨噬细胞向M2表型极化的潜力，从而减少关节炎症，促进软骨保护和修复。体外和体内研究的一致结果表明，尽管它们的理化性质不同，但它们能够减少与m1型巨噬细胞相关的促炎介质，同时增强与m2型巨噬细胞相关的抗炎介质的表达。这表明纳米材料可以通过重编程巨噬细胞来抑制OA的炎症微环境，并通过降低滑膜炎和软骨损伤来减缓疾病进展。通过影响巨噬细胞极化和促进再生环境，纳米技术可能为OA管理中更有效、更有针对性的策略铺平道路。

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引用次数: 0

Supercritical CO2-foamed hierarchically porous PLA/PBS-based scaffold for advanced bone regeneration 用于高级骨再生的超临界co2泡沫分层多孔PLA/ pbs基支架。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-15 DOI: 10.1016/j.bioadv.2025.214663

Shan Tang , Guobin Huang , Chengyong Li , Zhongming Li , Yuhui Xie , Feng Wu , Delong Xie , Dong Feng

This study presents a novel porous bone scaffold system (PBCMH) fabricated by melt blending and supercritical CO₂ (scCO₂) foaming, incorporating nano-hydroxyapatite (nHA), chitosan, polylactic acid (PLA), and polybutylene succinate (PBS). Four formulations with varying nHA content (0 %, 10 %, 20 %, 30 %) were evaluated to optimize the balance of structure, mechanical properties, and osteogenic bioactivity for bone regeneration. The scaffolds demonstrated interconnected porous networks with tunable pore sizes and mechanical strengths (57.2–184.3 μm). The PBCMH3 group (30 % nHA) exhibited the smallest average pore size, highest surface hydrophilicity (61.1°), and the best mechanical properties (elastic modulus ~4.26 MPa), resembling cancellous bone. Physicochemical analysis confirmed uniform dispersion of components and strong interfacial interactions. In vitro studies demonstrated that PBCMH3 significantly promoted rBMSC proliferation and osteogenic differentiation, as indicated by enhanced cytoskeletal organization, elevated alkaline phosphatase (ALP) activity, and increased mineral deposition. These in vitro findings were further supported by in vivo results: in a rat calvarial defect model, micro-CT and histological analyses confirmed superior bone regeneration in the PBCMH3 group, characterized by extensive new bone formation and the presence of mature lamellar bone. Importantly, no signs of systemic toxicity or pathological changes were observed in major organs, validating the biosafety of the scaffold. Together, these results underscore the potential of PBCMH3 as a promising scaffold for clinical bone tissue engineering, offering a comprehensive solution to the challenges of bone regeneration.

本研究提出了一种新型的多孔骨支架系统（PBCMH），采用熔融共混和超临界CO2 （scCO2）发泡，由纳米羟基磷灰石（nHA）、壳聚糖、聚乳酸（PLA）和聚丁二酸丁二酯（PBS）组成。评估了四种不同nHA含量（0%,10%,20%,30%）的配方，以优化结构，力学性能和骨再生成骨生物活性的平衡。该支架具有可调节孔径和机械强度（57.2 ~ 184.3 μm）的相互连接的多孔网络。PBCMH3 （30% nHA）的平均孔径最小，表面亲水性最高（61.1°），力学性能最佳（弹性模量4.26 MPa），类似松质骨。理化分析证实组分分散均匀，界面相互作用强。体外研究表明，PBCMH3显著促进rBMSC增殖和成骨分化，表现为细胞骨架组织增强，碱性磷酸酶（ALP）活性升高，矿物质沉积增加。这些体外研究结果得到了体内实验结果的进一步支持：在大鼠颅骨缺损模型中，显微ct和组织学分析证实了PBCMH3组具有较好的骨再生能力，其特征是广泛的新骨形成和成熟板层骨的存在。重要的是，在主要器官中未观察到系统性毒性或病理改变的迹象，验证了支架的生物安全性。总之，这些结果强调了PBCMH3作为临床骨组织工程支架的潜力，为骨再生挑战提供了全面的解决方案。

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引用次数: 0

Sustainable silk fibroin scaffolds for bone repair: assessing their osteogenic potential via AI-enhanced synchrotron imaging workflow 用于骨修复的可持续丝素蛋白支架：通过人工智能增强同步加速器成像工作流程评估其成骨潜力。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-13 DOI: 10.1016/j.bioadv.2025.214658

G. Dei Rossi , F. Buccino , E. Longo , G. Tromba , L.M. Vergani

Effective bone regeneration requires scaffolds capable of guiding and supporting new mineralized matrix formation. In this study, silk fibroin constructs cultured with human mesenchymal stem cells (hBMSCs) in the presence of either Fetal Bovine Serum (FBS) or Human Platelet Lysate (hPL) are evaluated for their osteogenic potential. A distinctive aspect of this work is the combined use of synchrotron X-ray imaging and a convolutional neural network for high-resolution in situ three-dimensional scaffold osteogenic potential assessment. This approach enables precise evaluation of bone matrix arrangement within the scaffold architecture. Two-dimensional analysis reveals increased mineralization in pores with an average radius of ~115 μm, area of ~4.0 × 10⁴ μm², and eccentricity of ~0.7 in hPL construct. The subsequent three-dimensional analysis extends these findings by quantifying the spatial distribution and connectivity of the mineralized matrix across the scaffold volume. It identifies pores with an equivalent radius between 110 and 120 μm, high surface area, and moderate sphericity (0.65–0.75) as optimal not only for mineral deposition but also for uniform 3D matrix propagation. Moreover, unsupervised clustering analysis also identifies optimal geometric interdependencies between pore size, surface area, and sphericity, offering new insights for rational design of high-performance scaffolds. The study demonstrates both the efficacy of silk fibroin scaffolds cultured with hPL in promoting bone regeneration and the relevance of a combined synchrotron imaging-artificial intelligence approach in quantitatively correlating three-dimensional porous geometry with regenerative outcomes.

有效的骨再生需要能够引导和支持新矿化基质形成的支架。在这项研究中，用人间充质干细胞（hBMSCs）培养丝素蛋白构建物，在胎牛血清（FBS）或人血小板裂解液（hPL）存在下，评估其成骨潜能。这项工作的一个独特方面是结合使用同步加速器x射线成像和卷积神经网络进行高分辨率原位三维支架成骨潜力评估。这种方法可以精确评估支架结构中的骨基质排列。二维分析表明，hPL构造的孔隙平均半径为~115 μm，面积为~4.0 × 104 μm2，偏心率为~0.7。随后的三维分析通过量化整个支架体积的矿化基质的空间分布和连通性来扩展这些发现。等效半径在110 ~ 120 μm之间、比表面积大、球度适中（0.65 ~ 0.75）的孔隙不仅适合矿物沉积，而且适合均匀的三维基质传播。此外，无监督聚类分析还发现了孔径、表面积和球形度之间的最佳几何关系，为高性能支架的合理设计提供了新的见解。该研究证明了用hPL培养的丝素蛋白支架在促进骨再生方面的功效，以及同步加速器成像和人工智能相结合的方法在定量关联三维多孔几何形状与再生结果方面的相关性。

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引用次数: 0

Semi-degradable biomimetic double-layer small diameter vascular graft for arteriovenous fistula in large animals 半可降解仿生双层小直径血管移植物用于大型动物动静脉瘘。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-13 DOI: 10.1016/j.bioadv.2025.214655

Zhiping Fang , Yonghao Xiao , Jubo Li , Hailei Li , Xin Wu , Lin Ye , Zenggguo Feng

A double layer small diameter vascular graft (SDVG) was fabricated by sequential electrospinning. The inner layer was composed by three kinds of biodegradable poly (ε-caprolactone) (PCL) fibers with three different molecular weights to induce endothelial regeneration and the outer layer comprised non-degradable thermoplastic polyurethane (TPU) fibers and PCL fibers with the numerical molecular weight of 80,000 g/mol to provide long-term mechanical support. The SDVG was further heparinized through “erosion and graft” strategy. The surface heparin content, the clotting time and the mechanical properties were evaluated in vitro. Then, the double layer SDVG was implanted into the sheep for six months as the arteriovenous fistula connecting carotid artery and jugular vein. The Doppler ultrasonic measurement and angiography showed the patency of the transplanted SDVGs and the in situ puncture test exhibited the potential of the SDVG for hemodialysis. H&E and Masson staining characterized the remodeling of the inner layer, whereas Safranin O and von Kossa staining demonstrated the regeneration of extracellular matrix and the absence of the calcification in the implanted SDVG. More importantly, the perfect regeneration of endothelium on the lumen of the SDVG was proven by CD31 staining. Consequently, the as-prepared SDVG showed the potential to be the artificial arteriovenous fistula in the clinic.

采用序贯静电纺丝法制备了双层小直径血管移植物。内层由3种不同分子量的可生物降解聚（ε-己内酯）（PCL）纤维组成，用于诱导内皮细胞再生；外层由不可降解的热塑性聚氨酯（TPU）纤维和分子量为80000 g/mol的PCL纤维组成，提供长期的机械支持。通过“侵蚀和移植”策略进一步使SDVG肝素化。体外测定其表面肝素含量、凝血时间和力学性能。然后将双层SDVG作为连接颈动脉和颈静脉的动静脉瘘植入绵羊体内6个月。多普勒超声测量和血管造影显示移植的SDVG通畅，原位穿刺试验显示SDVG有血液透析的潜力。H&E和Masson染色显示内层重塑，而Safranin O和von Kossa染色显示植入的SDVG细胞外基质再生，没有钙化。更重要的是，CD31染色证实了SDVG管腔内皮细胞的完美再生。因此，制备的SDVG在临床上具有作为人工动静脉瘘的潜力。

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引用次数: 0

Fabrication, characterization, and in vivo biosafety evaluation of starch-based bioplastic as a sustainable alternative to polystyrene 淀粉基生物塑料作为聚苯乙烯可持续替代品的制备、表征和体内生物安全性评价。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-13 DOI: 10.1016/j.bioadv.2025.214659

Muhammad Usman Zahid , Hashaam Akhlaq , Khazeena Atta , Aneesa Javaid , Faiza Rasheed

The widespread use of synthetic plastics such as polystyrene raises concerns over long-term environmental persistence and biological toxicity. Although bioplastics offer a promising alternative, their in vivo biosafety and comparative evaluation with conventional plastics remain insufficiently explored. The study aimed to develop and characterize a starch-based bioplastic derived from Eriobotrya japonica (loquat) seeds and to evaluate its in vivo biosafety in Swiss albino mice. The novelty of this work lies in utilizing an underreported starch source and performing a direct comparison with polystyrene to establish a biological benchmark. Differential Scanning Calorimetry revealed low enthalpies of fusion (2.55 J/g) and crystallization (9.24 J/g), confirming the predominantly amorphous and thermally soft nature of the film. These characteristics, combined with moderate flexibility and moisture permeability, suggest biological compatibility for in vivo applications. Hematological analysis showed elevated white blood cell counts in the polystyrene group (6.75 ± 0.7 × 10³/cmm) compared to the starch-based bioplastic group (3.7 ± 0.4 × 10³/cmm), which remained within the normal range. Histological examination revealed normal tissue architecture in the liver, kidney, and heart of mice treated with starch-based bioplastic, while polystyrene caused mild hepatocellular degeneration and early myocardial hypertrophy. Overall, the results confirm the biosafety and biocompatibility of the prepared starch-based bioplastic as a sustainable alternative to petroleum-based plastics for environmental and biomedical applications.

聚苯乙烯等合成塑料的广泛使用引发了人们对长期环境持久性和生物毒性的担忧。虽然生物塑料提供了一个很有前途的替代品，但其体内生物安全性和与传统塑料的比较评价仍然没有得到充分的探讨。本研究旨在开发和表征从枇杷种子中提取的淀粉基生物塑料，并评估其在瑞士白化小鼠体内的生物安全性。这项工作的新颖之处在于利用一种未被报道的淀粉来源，并与聚苯乙烯进行直接比较，以建立生物基准。差示扫描量热法显示，该薄膜的熔合焓低（2.55 J/g），结晶焓低（9.24 J/g），证实了该薄膜主要为无定形和热软性质。这些特性，结合适度的灵活性和透湿性，表明生物相容性在体内应用。血液学分析显示，与淀粉基生物塑料组（3.7±0.4 × 103/cmm）相比，聚苯乙烯组的白细胞计数（6.75±0.7 × 103/cmm）升高，但仍在正常范围内。组织学检查显示，淀粉基生物塑料处理小鼠的肝、肾和心脏组织结构正常，而聚苯乙烯引起轻度肝细胞变性和早期心肌肥大。总的来说，研究结果证实了制备的淀粉基生物塑料的生物安全性和生物相容性，作为环境和生物医学应用中石油基塑料的可持续替代品。

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引用次数: 0

Exploiting mechanistic insights to improve the delivery of nanomaterials and extracellular vesicles to tumors 利用机制来改善纳米材料和细胞外囊泡对肿瘤的递送。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-11 DOI: 10.1016/j.bioadv.2025.214657

Daniela León García , Karen Bolaños , Pamela Contreras , David Silva , Rodrigo Vásquez-Contreras , Eyleen Araya , Marcelo J. Kogan , Andrew F.G. Quest

The main current challenges in oncology therapy are (1) improving the targeting of chemotherapeutics to tumors and (2) developing alternative treatments for metastatic tumors. Nanomedicine can provide an answer to these problems; however, the delivery of sufficient therapeutic nanoparticles (NPs) to tumors remains a huge challenge in nanomaterial-based treatments. Extracellular vesicles (EVs) are key participants in intercellular communication processes that can be combined with nanomaterials to enhance their targeting. Available evidence indicates that Caveolin-1 (CAV1) when expressed in cancer cells modulates the protein cargos of EVs such as to enhance migration, invasion and metastasis of recipient cancer cells. Furthermore, these effects are favored by CAV1 phosphorylation at tyrosine 14. Considering this role of CAV1 and its phosphorylation on Y14 in the EV cargo sorting of certain cell adhesion proteins, such as β3 and β5 integrins important for EV tropism, we evaluated the biodistribution of EVs loaded with gold nanoparticles from B16F10 cells expressing wild-type (CAV1) phosphomimetic (CAV1/Y14E) and phospho-null (CAV1/Y14F) in a pre-clinical murine model of lung metastasis. The experiments revealed that EVs(CAV1)-AuNPs and EVs(CAV1/Y14E)-AuNPs reached more rapidly and accumulated to a greater extent in small metastatic lung tumors compared to control EVs or EVs(CAV1/Y14F). As expected, a higher accumulation of gold in vitro in B16F10 cells, as well as in vivo in small metastatic lung nodules was detected when EVs(CAV1) or EVs(CAV1/Y14E) were used as vehicles for the AuNPs. Thus, CAV1 expression enhances the accumulation and targeting of AuNP-loaded melanoma cell-derived EVs to small metastatic lung tumors formed by their parental B16F10 cells. Importantly, the enhanced targeting capacity of EVs(CAV1)-AuNPs was found to be dependent on CAV1 phosphorylation at tyrosine 14.

目前肿瘤治疗的主要挑战是：(1)提高化疗药物对肿瘤的靶向性；(2)开发转移性肿瘤的替代治疗方法。纳米医学可以为这些问题提供答案；然而，在基于纳米材料的治疗中，向肿瘤输送足够的治疗性纳米粒子（NPs）仍然是一个巨大的挑战。细胞外囊泡（EVs）是细胞间通讯过程的关键参与者，可以与纳米材料结合以增强其靶向性。现有证据表明，在癌细胞中表达Caveolin-1 （CAV1）时，可调节ev的蛋白质货物，如增强受体癌细胞的迁移、侵袭和转移。此外，这些作用受到CAV1酪氨酸14磷酸化的支持。考虑到CAV1及其在Y14上的磷酸化在某些细胞粘附蛋白（如β3和β5整合素）的EV货物分选中的作用，我们评估了来自表达野生型（CAV1）拟磷（CAV1/Y14E）和无磷（CAV1/Y14F）的B16F10细胞的金纳米颗粒在临床前小鼠肺转移模型中的生物分布。实验表明，与对照ev或ev （CAV1/Y14F）相比，ev (CAV1)-AuNPs和ev (CAV1/Y14E)-AuNPs在小转移性肺肿瘤中到达和积累的速度更快，积累的程度更大。正如预期的那样，当使用ev （CAV1）或ev （CAV1/Y14E）作为aunp的载体时，在体外B16F10细胞中以及体内小转移性肺结节中检测到更高的金积累。因此，CAV1的表达增强了装载aunp的黑色素瘤细胞源性ev对由亲代B16F10细胞形成的小转移性肺肿瘤的积累和靶向。重要的是，研究发现ev (CAV1)-AuNPs的靶向能力增强依赖于CAV1酪氨酸14位点的磷酸化。

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引用次数: 0

Biphasic bone-mimicking constructs containing silk fibroin peptide enhanced bone regeneration in segmental defects in rats 含有丝素蛋白肽的双相骨模拟结构促进大鼠节段性骨缺损的骨再生

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-11 DOI: 10.1016/j.bioadv.2025.214650

Amin Ebrahimi Sadrabadi , Seyed Shahriar Arab , Amir Kamali , Saghar Karimi , Mohamadreza Baghaban Eslaminejad , Samaneh Hosseini

To advance bone tissue engineering, it is essential to design and integrate biomaterials that can closely mimic the microarchitecture of native tissue and enhance biological functionality. This study presents a biphasic bone-mimicking construct that integrates decellularized extracellular matrix (dECM), calcium phosphate cement (CPC), and tailored silk fibroin (SFp) peptides to synergize with biological and mechanical cues for enhanced regeneration. The dECM/CPC hydrogel (dECM/CPC-Hy) layer provides robust structural support, whereas the inner SFp-functionalized dECM hydrogel drives cellular activity. Dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy measurements confirmed distinct secondary structures and zeta potentials ranging from −8.8 ± 0.13 mV to −1.3 ± 0.09 mV for SFp1 and SFp2, respectively. MTT assays demonstrated nontoxicity for all peptides over a concentration range from 10 μg/ml to 200 μg/ml. SFp1 upregulated the expression of the Col1, Opn, Ocn and CD31 genes after 21 days in the dECM/SFp/CPC construct. In a rat radius defect model, the dECM/SFp/CPC construct resulted in significant bone regeneration after 12 weeks, as evidenced by micro-CT and X-ray imaging. In conclusion, the dECM/SFp/CPC construct shows great potential as an advanced biomaterial for bone tissue engineering, combining the biological cues of dECM and SFp with the mechanical properties of CPC to enhance bone regeneration.

为了推进骨组织工程的发展，设计和整合能够近似模拟天然组织微结构并增强生物功能的生物材料是必不可少的。本研究提出了一种双相骨模拟结构，该结构整合了脱细胞细胞外基质（dECM）、磷酸钙水泥（CPC）和定制丝素蛋白（SFp）肽，与生物和机械线索协同作用，以增强再生。dECM/CPC水凝胶（dECM/CPC- hy）层提供强大的结构支持，而内部的sfp功能化的dECM水凝胶驱动细胞活动。动态光散射（DLS）和圆二色性（CD）光谱测量证实SFp1和SFp2具有明显的二级结构，zeta电位范围分别为- 8.8±0.13 mV至- 1.3±0.09 mV。MTT试验表明，在10 μg/ml至200 μg/ml的浓度范围内，所有肽均无毒。在dECM/SFp/CPC构建中，SFp1在21天后上调Col1、Opn、Ocn和CD31基因的表达。在大鼠桡骨缺损模型中，显微ct和x射线成像证明，12周后，dECM/SFp/CPC构建产生了显著的骨再生。综上所述，dECM/SFp/CPC构建体将dECM和SFp的生物学特性与CPC的力学特性结合起来，促进骨再生，作为一种先进的骨组织工程生物材料具有很大的潜力。

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引用次数: 0

Mesenchymal stem cell-derived small extracellular vesicles loaded with miRNA-4488 alleviate chemotherapy-induced premature ovarian insufficiency via mitigation of apoptosis and oxidative stress 装载miRNA-4488的间充质干细胞来源的细胞外小泡通过减轻细胞凋亡和氧化应激减轻化疗诱导的卵巢早衰。

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-11 DOI: 10.1016/j.bioadv.2025.214656

Shi-Xian Li , Shi-Yao Wei , Chai Li , Ya-Le Sheng , Yun Liu , Na Xu

Chemotherapy-induced premature ovarian insufficiency (POI) can disrupt endocrine homeostasis in female cancer patients. Since current therapeutic options remain inadequate, there is an urgent need to develop new strategies for POI prevention or treatment. Small extracellular vesicles (sEVs) derived from stem cells are recognized for their capacities in tissue repair, regeneration, and drug delivery. In this study, a microRNA delivery system was constructed by loading miRNA-4488 into bone marrow mesenchymal stem cell-derived sEVs via electroporation. The prepared sEVs-miR4488 significantly inhibited macrophage inflammation and promoted fibroblast cell migration and proliferation. In oxaliplatin-induced ovarian granulosa cells, sEVs-miR4488 reduced the expression of Bax and increased the expression of Bcl-2, demonstrating the anti-apoptotic activity. Additionally, oxaliplatin-induced reactive oxygen species production and mitochondrial depolarization were both decreased following treatment with sEVs-miR4488. These therapeutic effects were further confirmed in a POI mouse model. Bioinformatics analysis using FunRich and GO-BP revealed the involvement of multiple signaling pathways, and the NF-κB signaling pathway was verified to be downregulated in the protective mechanism mediated by miR-4488. Collectively, it provides a new strategy for the prevention and treatment of POI using sEVs-miR4488 in this study.

化疗诱导的卵巢早衰（POI）可破坏女性癌症患者的内分泌稳态。由于目前的治疗方案仍然不足，因此迫切需要制定预防或治疗POI的新战略。来自干细胞的小细胞外囊泡（sev）因其在组织修复、再生和药物输送方面的能力而得到认可。在这项研究中，通过电穿孔将miRNA-4488装载到骨髓间充质干细胞衍生的sev中，构建了一个microRNA递送系统。制备的sews - mir4488能显著抑制巨噬细胞炎症，促进成纤维细胞迁移和增殖。在奥沙利铂诱导的卵巢颗粒细胞中，sews - mir4488降低Bax的表达，增加Bcl-2的表达，显示出抗凋亡活性。此外，用sews - mir4488治疗后，奥沙利铂诱导的活性氧产生和线粒体去极化均减少。这些治疗效果在POI小鼠模型中得到进一步证实。利用FunRich和GO-BP进行生物信息学分析，发现miR-4488介导的保护机制涉及多种信号通路，证实NF-κB信号通路下调。综上所述，本研究为sews - mir4488预防和治疗POI提供了新的策略。

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引用次数: 0

Constructing Bi2Te3-Ti3C2TX Schottky junction in PCL scaffold to amplify photo-thermal-electricity coupling effect for accelerating cell osteogenic differentiation 构建PCL支架Bi2Te3-Ti3C2TX Schottky结增强光热-电耦合效应，促进细胞成骨分化

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2025-12-09 DOI: 10.1016/j.bioadv.2025.214652

Xiang Chen , Huixing Li , Yidong Zhong , Yanzhi Ge

Bismuth telluride (Bi₂Te₃) exhibits great potential in thermoelectric therapy for bone defect repair due to its excellent thermoelectric conversion and electron-phonon decoupling properties. Nonetheless, its therapeutic efficacy is restricted by excessively low carrier mobility, insufficient body temperature gradient, and fast charge recombination. Herein, Bi₂Te₃ was bridged on the -O⁻ functional group of Mxene (Ti₃C₂T_x) using in-situ sedimentation to construct a Bi₂Te₃-Ti₃C₂T_X Schottky junction responsive to near-infrared (NIR) light. Then introduced into polycaprolactone (PCL) particles to prepare bone scaffold. Under NIR irradiation, Ti₃C₂T_X acts as a metalloid to generate coherent electron oscillations, converting light energy into lattice heat and providing sufficient temperature gradient for activating thermoelectric effects. Subsequently, Ti₃C₂T_X and Bi₂Te₃ form a Schottky junction to filter low-energy carriers, further increasing the average carrier energy to improve carrier mobility. Furthermore, the interface dipole field in heterojunctions can directionally drive electron-hole separation. Thermal imaging display scaffold possesses a temperature gradient of 30 °C. Results prove a significant optimization in carrier mobility and charge separation, resulting 45 % and 3.5-fold increase in Seebeck coefficient and current density respectively. The enhanced electrical signal can facilitate Ca²⁺ influx, synergizing photothermal sensitive HSP70 to promote actin cytoskeleton and cell proliferation. Moreover, current can upregulate the expression of BMP-2 and osteogenic related genes, increasing ALP and ARS by 2.5-fold to accelerate osteoblast differentiation.

碲化铋（Bi2Te3）由于其优异的热电转换和电子-声子去耦特性，在骨缺损修复的热电治疗中表现出巨大的潜力。但其治疗效果受载流子迁移率过低、体温梯度不足、电荷重组快等因素的限制。本文采用原位沉积法将Bi2Te3桥接在Mxene （Ti3C2Tx）的-O -官能团上，构建了一个响应近红外（NIR）光的Bi2Te3- Ti3C2Tx肖特基结。然后引入聚己内酯（PCL）颗粒制备骨支架。在近红外辐射下，Ti3C2TX作为类金属产生相干电子振荡，将光能转化为晶格热，为热电效应的激活提供了足够的温度梯度。随后，Ti3C2TX与Bi2Te3形成肖特基结滤波低能量载流子，进一步提高载流子平均能量，提高载流子迁移率。此外，异质结中的界面偶极子场可以定向驱动电子-空穴分离。热成像显示支架具有30°C的温度梯度。结果表明，在载流子迁移率和电荷分离方面进行了显著优化，Seebeck系数和电流密度分别提高了45%和3.5倍。增强的电信号促进Ca2+内流，协同光热敏感的HSP70，促进肌动蛋白细胞骨架和细胞增殖。此外，电流可上调BMP-2和成骨相关基因的表达，使ALP和ARS增加2.5倍，加速成骨细胞的分化。

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引用次数: 0