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Coaxial Electrospray of Nanodrug-Loaded Porous Polylactic Acid/Poly(Ethylene Oxide) Core–Shell Microparticles for Intrapulmonary Drug Delivery 载药多孔聚乳酸/聚环氧乙烷核壳微粒子的同轴电喷雾肺内给药研究
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-09-12 DOI: 10.1002/jbm.a.37987
Chi Wang, Dandan Guo, Juntao Luo, Yingge Zhou

Biocompatible nano-to-microscale particles offer significant advantages for therapeutic applications, particularly in targeted and sustained drug delivery for lung diseases such as chronic obstructive pulmonary disease (COPD). This study focuses on the fabrication of porous core–shell microparticles encapsulating bioactive telodendrimer (TD) nanodrug carriers using electrospray technology. The microparticles were designed to enhance pulmonary drug delivery by optimizing particle size (1–5 μm) and morphology for deep lung deposition and controlled drug release. The effects of solution viscosity and surface tension on microparticle formation were systematically investigated. Results demonstrated that higher polymer concentration and controlled electrospray parameters yielded spherical microparticles with uniform porosity, essential for sustained drug release. Surfactant addition reduced particle size and enhanced pore formation but introduced challenges such as morphological variability. In vitro cytotoxicity, hemolysis, and drug release studies confirmed the biocompatibility and therapeutic potential of the fabricated microparticles. The findings highlight the promise of electrospray-derived core–shell microparticles for non-invasive COPD treatment, warranting further exploration into polymer-solvent interactions and formulation refinements for optimized drug delivery.

生物相容性纳米到微尺度颗粒为治疗应用提供了显著的优势,特别是在慢性阻塞性肺疾病(COPD)等肺部疾病的靶向和持续药物递送方面。本研究主要研究了利用电喷雾技术制备包封生物活性端突分子(TD)纳米药物载体的多孔核壳微粒子。通过优化颗粒尺寸(1 ~ 5 μm)和颗粒形态,设计微颗粒以增强肺部药物传递,促进肺深部沉积和药物控释。系统地研究了溶液粘度和表面张力对微粒形成的影响。结果表明,较高的聚合物浓度和控制的电喷雾参数可以获得均匀孔隙度的球形微颗粒,这对药物的持续释放至关重要。表面活性剂的加入降低了颗粒尺寸,增强了孔隙形成,但也带来了诸如形态变异等挑战。体外细胞毒性、溶血和药物释放研究证实了制备的微颗粒的生物相容性和治疗潜力。这些发现强调了电喷雾衍生的核壳微粒在非侵入性COPD治疗中的前景,需要进一步探索聚合物-溶剂相互作用和优化药物递送的配方。
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引用次数: 0
Therapeutic Effect of a Composite Acellular Matrix/Hyaluronic Acid Thermosensitive Hydrogel for the Interstitial Cystitis/Bladder Pain Syndrome in a Rat Model 复合脱细胞基质/透明质酸热敏水凝胶对大鼠间质性膀胱炎/膀胱痛综合征的治疗作用
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-09-03 DOI: 10.1002/jbm.a.37973
Haichao Liu, Wei Guo, Jianzhong Zhang, Wei Tang, Fei Wang, Jiaxing Zhang, Peng Zhang

This study investigated the therapeutic effects of a composite small intestinal submucosa decellularized extracellular matrix/hyaluronic acid (HA)-incorporated thermosensitive hydrogel (HA-Gel) on interstitial cystitis (IC) in rats. The HA-Gel was fabricated using rabbit small intestinal submucosa-derived extracellular matrix as a thermosensitive scaffold combined with HA, and an IC rat model was established using the UPK3A65–84 peptide. Rats were divided into five groups: IC group, IC + HA group, IC + Gel group, IC + HA-Gel group, and a non-modeled control group. After 14 days of treatment, urodynamic analysis revealed that the HA, IC + Gel, and IC + HA-Gel groups exhibited significantly increased interval voiding times and maximum bladder capacities compared to the IC group, with the most pronounced improvement observed in the IC + HA-Gel group (p < 0.01). Histopathological evaluation revealed reduced mucosal edema, inflammatory cell infiltration, and mucosal denudation in all treatment groups, particularly in the IC + HA-Gel group (p < 0.01). Mast cell infiltration was also markedly suppressed by HA-Gel (p < 0.01). Immunofluorescence and molecular analyses further indicated that HA, Gel, and HA-Gel effectively downregulated the expression levels of CD3, ICAM-1, TNF-α, IFN-γ, IL-1β, IL-6, and TRPM8 in bladder tissues, with the most significant reductions observed in the IC + HA-Gel group (p < 0.01). Notably, both Gel and HA-Gel remained detectable in bladder tissues for over 14 days post-administration. In conclusion, HA-Gel not only improves voiding function and bladder capacity in IC rats but also suppresses inflammatory responses, demonstrating promising therapeutic potential and providing new insights for the clinical management of IC/bladder pain syndrome (BPS).

本研究探讨了复合小肠黏膜下脱细胞细胞外基质/透明质酸(HA)掺入的热敏水凝胶(HA- gel)对大鼠间质性膀胱炎(IC)的治疗作用。以兔小肠粘膜下源性细胞外基质为热敏支架与HA结合制备HA- gel,并利用UPK3A65-84肽建立IC大鼠模型。将大鼠分为5组:IC组、IC + HA组、IC +凝胶组、IC + HA-凝胶组和非模型对照组。治疗14天后,尿动力学分析显示,与IC组相比,HA、IC + Gel和IC + HA-Gel组的间隔排尿时间和最大膀胱容量显著增加,其中IC + HA-Gel组的改善最为明显(p < 0.01)。组织病理学评估显示,在所有治疗组,特别是IC + HA-Gel组,粘膜水肿、炎症细胞浸润和粘膜剥落均有所减轻(p < 0.01)。HA-Gel还能显著抑制肥大细胞的浸润(p < 0.01)。免疫荧光和分子分析进一步表明,HA、Gel和HA-Gel可有效下调膀胱组织中CD3、ICAM-1、TNF-α、IFN-γ、IL-1β、IL-6和TRPM8的表达水平,其中以IC + HA-Gel组下调幅度最大(p < 0.01)。值得注意的是,凝胶和ha -凝胶在给药后14天内仍可在膀胱组织中检测到。综上所述,HA-Gel不仅可以改善IC大鼠的排尿功能和膀胱容量,还可以抑制炎症反应,具有良好的治疗潜力,为IC/膀胱疼痛综合征(BPS)的临床治疗提供了新的见解。
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引用次数: 0
Implantable Medical Devices, Biomaterials, and the Foreign Body Response: A Surgical Perspective 植入式医疗装置、生物材料和异物反应:外科视角
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-09-03 DOI: 10.1002/jbm.a.37983
Nikita Kalashnikov, Jake Barralet, Joshua Vorstenbosch

Implantable medical devices improve quality of life and reduce mortality by restoring the form and function of the human body. Their biomaterial surface components in contact with tissues are, however, susceptible to the host's foreign body response, which drives inflammation and implant fibrous encapsulation. When dysregulated, this response causes implant-related patient morbidity and device failure, ultimately requiring revision surgery. Here, we review the roles that the biomaterial, the host, and the implantation surgery play in the foreign body response. Taking commonly-used implantable medical devices as examples, we first describe the foreign body response; then, we examine the factors influencing it, and finally, we propose ideas of how it can be controlled perioperatively in an attempt to minimize implant-related complications.

植入式医疗器械通过恢复人体的形态和功能来提高生活质量,降低死亡率。然而,与组织接触的生物材料表面成分容易受到宿主异物反应的影响,从而导致炎症和植入纤维包埋。当失调时,这种反应会导致与植入物相关的患者发病率和装置失效,最终需要翻修手术。在此,我们综述了生物材料、宿主和植入手术在异物反应中的作用。以常用的植入式医疗器械为例,首先描述异物反应;然后,我们检查了影响它的因素,最后,我们提出了如何在围手术期控制它的想法,以尽量减少与种植体相关的并发症。
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引用次数: 0
Gyroid-Structured Scaffolds Guide Uniform Ossification and Modulate Vascular Morphology During Rat Calvarial Bone Defect Regeneration 螺旋结构支架在大鼠颅骨骨缺损再生过程中引导均匀骨化和调节血管形态
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-30 DOI: 10.1002/jbm.a.37978
Guoyan Xian, Baptiste Charbonnier, Morad Bensidhoum, Esther Potier, Morgane Margottin, Puyi Sheng, Christine Chappard, Hervé Petite, Fani Anagnostou, David Marchat, Delphine Logeart-Avramoglou

Bone repair procedures rely on osteoconductive material scaffolds that guide and promote bone ingrowth through their architecture. This study investigated how the bone formation and vascularization are modulated within gyroid macroporous scaffolds during the regeneration of rat calvarial bone defects. It compared scaffold-guided regeneration to spontaneous healing through 3D analysis of both ossification and vascularization. Two disc-shaped bioceramic scaffolds with either wide or narrow porous geometries were designed and fabricated to facilitate or limit bone ingrowth. While overall ossification dynamics were similar regardless of repair efficacy, scaffold presence modulated the ossification pattern, promoting bone formation throughout by conduction. The scaffolds also influenced vascular network morphology but not its density. Notably, 3D imaging revealed a negative correlation between vascularization and bone formation in scaffold-filled defects, while no correlation was found in empty defects. This result suggests that ossification during calvarial regeneration relies on additional pro-osteogenic factors beyond robust vascularization. These insights are valuable for optimizing scaffold-based strategies to enhance bone regeneration in calvarial defects.

骨修复过程依赖于骨传导材料支架,通过其结构引导和促进骨向内生长。本研究研究了大鼠颅骨骨缺损再生过程中骨形成和血管形成在回状大孔支架内的调节。通过对骨化和血管形成的3D分析,比较了支架引导下的再生与自发愈合。设计和制造了两种具有宽或窄多孔几何形状的圆盘状生物陶瓷支架,以促进或限制骨向内生长。尽管无论修复效果如何,整体骨化动力学都是相似的,但支架的存在调节了骨化模式,通过传导促进了整个骨形成。支架也影响血管网形态,但不影响其密度。值得注意的是,3D成像显示支架填充缺损的血管化与骨形成呈负相关,而空心缺损的血管化与骨形成无相关。这一结果表明,颅骨再生过程中的骨化依赖于除强大的血管化之外的其他促成骨因素。这些见解对于优化基于支架的策略来增强颅骨缺损的骨再生是有价值的。
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引用次数: 0
Efficacy of 3D-Printed Bioactive Glass Tetrahedral Particles for Vertical Bone Regeneration: A Comparative Study 3d打印生物活性玻璃四面体颗粒垂直骨再生效果的比较研究
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-30 DOI: 10.1002/jbm.a.37980
Wenjie Wang, Liya Ai, Lingling Zheng, Dan Chen, Raffaella Aversa, Antonio Apicella, Chao Wang, Yubo Fan

This study was designed to systematically evaluate the osteogenic efficacy of 3D-printed tetrahedral bioactive glass particles in vertical bone regeneration and compare their performance with that of conventional bone substitute materials. In this investigation, 3D tetrahedral bioactive glass particles were fabricated using digital light processing (DLP) additive manufacturing technology. The structural integrity and chemical composition of the particles were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD) to confirm their conformity to design specifications. Additionally, three commercially available bone substitutes—Bio-Oss, PerioGlas, and Osteon—were employed as control materials for comparative analysis. In the experimental phase, four types of particulate materials were loaded into titanium buckets, which were then implanted on the calvarial surface of New Zealand white rabbits with surgically drilled cortical perforations at the implantation site. Micro-computed tomography (micro-CT) and histological evaluations were performed at 4 weeks and 12 weeks post-implantation. The results demonstrated that at 4 weeks, the height of new bone formation induced by the 3D-printed tetrahedral bioactive glass particles was 4.67 ± 0.34 mm, with a new bone proportion of 12.42% ± 3.81% and a new bone marrow proportion of 11.58% ± 1.63%. By 12 weeks, no statistically significant differences were observed among the groups in terms of new bone height, new bone proportion, or new bone marrow proportion. However, the 3D-printed particles exhibited a more homogeneous distribution of newly formed bone tissue. The osteogenic efficacy of 3D-printed tetrahedral bioactive glass particles in vertical bone regeneration is comparable to that of traditional bone substitute materials. However, their distinctive tetrahedral structure offers superior uniformity in bone growth. These results indicate that 3D printing technology holds promise for the development of bone substitute materials and merits further optimization as well as clinical translation.

本研究旨在系统评价3d打印四面体生物活性玻璃颗粒在垂直骨再生中的成骨效果,并将其与常规骨替代材料的性能进行比较。在本研究中,采用数字光处理(DLP)增材制造技术制备了三维四面体生物活性玻璃颗粒。采用扫描电子显微镜(SEM)、能谱仪(EDS)和x射线衍射仪(XRD)对颗粒的结构完整性和化学成分进行了表征,确认其符合设计要求。此外,三种市售骨替代物- bio - oss, PerioGlas和osteon -作为对照材料进行比较分析。在实验阶段,将四种颗粒材料装入钛桶中,植入新西兰大白兔颅骨表面,植入部位经手术钻孔形成皮质穿孔。植入后4周和12周进行显微计算机断层扫描(micro-CT)和组织学评估。结果表明,3d打印的四面体生物活性玻璃颗粒在第4周诱导的新骨形成高度为4.67±0.34 mm,新骨比例为12.42%±3.81%,新骨髓比例为11.58%±1.63%。12周时,各组新骨高度、新骨比例、新骨髓比例差异均无统计学意义。然而,3d打印的颗粒表现出更均匀的新形成的骨组织分布。3d打印四面体生物活性玻璃颗粒在垂直骨再生中的成骨效果与传统骨替代材料相当。然而,它们独特的四面体结构为骨骼生长提供了优越的均匀性。这些结果表明,3D打印技术在骨替代材料的开发中具有广阔的前景,值得进一步优化和临床应用。
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引用次数: 0
3D-Printed Precision Porous Scaffolds Promote Healing In Vivo 3d打印精密多孔支架促进体内愈合
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-30 DOI: 10.1002/jbm.a.37981
Guoyao Chen, Sharon Creason, Ningjing Chen, Adia Kirkham, Le Zhen, Shijie Zhang, Kan Wu, Buddy Ratner

Precision porous scaffolds hold promise for tissue engineering and regenerative medicine due to their ability to support cell ingrowth and vascularization and mitigate the foreign body reaction (FBR). In previous work, we demonstrated that vat photopolymerization 3D printing enables the fabrication of porous scaffolds with 40 μm interconnected cubical pores. This study aims to do a preliminary evaluation of cellular responses and the FBR to 3D-printed scaffolds with 40 μm cubical pores, in comparison with template-fabricated spherical pores (optimized for healing) and non-porous slabs (negative control). The results indicate that porous scaffolds, regardless of pore geometry, outperform non-porous structures in mitigating the FBR, promoting tissue regeneration, and triggering vascularization. This is the first paper demonstrating the pro-healing property of high-resolution 3D-printed 40 μm cubical pore scaffolds. These findings underscore the potential of 3D-printed porous scaffolds to advance patient-specific therapies, support soft (such as brain and blood vessel) and hard tissue (such as bone) repair, and improve healing outcomes in regenerative medicine applications.

精密多孔支架由于其支持细胞向内生长和血管形成以及减轻异物反应(FBR)的能力,在组织工程和再生医学中具有前景。在之前的工作中,我们证明了还原光聚合3D打印可以制造具有40 μm相互连接的立方孔的多孔支架。本研究旨在初步评估具有40 μm立方孔的3d打印支架的细胞反应和FBR,并与模板制造的球形孔(优化的愈合)和无孔板(阴性对照)进行比较。结果表明,无论孔隙几何形状如何,多孔支架在减轻FBR、促进组织再生和触发血管化方面都优于非多孔结构。这是第一篇展示高分辨率3d打印40 μm立方孔支架促愈合特性的论文。这些发现强调了3d打印多孔支架在推进患者特异性治疗、支持软组织(如大脑和血管)和硬组织(如骨骼)修复以及改善再生医学应用中的愈合效果方面的潜力。
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引用次数: 0
Design of a Corrugated Vascular Graft with Enhanced Compliance and Kink Resistance 具有增强顺应性和抗扭结性的波纹血管移植物的设计
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-15 DOI: 10.1002/jbm.a.37975
Andrew Robinson, Juan S. Herrera Duran, David Jiang, Jonathan Leung, Madeline Laude, Abbey Nkansah, Leopold Guo, Lucas Timmins, Elizabeth Cosgriff-Hernandez

The development of a small-diameter vascular graft for coronary artery bypass grafting necessitates a balance of key biomechanical properties to prevent failure. Prior iterative design of a multilayer vascular graft achieved arterial compliance-matching to prevent failure due to intimal hyperplasia while retaining sufficient burst pressure and suture retention strength. Although promising, graft kinking prevented long-term evaluation in vivo. To enhance kink resistance, a post-electrospinning molding method was developed to impart a corrugated geometry. Corrugations enhance kink resistance during bending through expansion and folding of the pleats to prevent ovalization and subsequent buckling. The corrugated graft significantly improved kink resistance with kink radii similar to synthetic grafts used in the clinic. In contrast to prior literature, the corrugated grafts displayed compliance values in the range of arterial values (10.4%/mmHg × 10−2 ± 0.3%/mmHg × 10−2) for improved graft-artery compliance-matching. A finite element (FE) model of compliance was used to elucidate the effect of corrugated geometry on graft compliance. The FE-predicted compliance values agreed well with experimental results and demonstrated an increase in Lagrange strain magnitude of the corrugated valleys that was correlated with a higher luminal compliance. To ensure clinical utility of corrugated grafts, candidate grafts were tested for suture retention strength, burst pressure, and stability under physiological loading. The corrugated graft retained biomechanical properties above or similar to reported values of the saphenous vein, demonstrating suitability for implantation. Finally, no significant change in graft dimensions demonstrated stability of the post-fabrication corrugation geometry after 30 days under pulsatile flow. A small-diameter vascular graft with this unique combination of biomechanical properties has the potential to improve long-term outcomes in coronary artery bypass graft procedures.

发展用于冠状动脉旁路移植术的小直径血管移植物需要平衡关键的生物力学特性以防止失败。先前多层血管移植物的迭代设计实现了动脉顺应性匹配,以防止由于内膜增生而导致的失败,同时保持足够的破裂压力和缝合保持强度。虽然很有希望,但移植物扭结阻碍了体内的长期评估。为了提高扭结阻力,开发了一种后静电纺丝成型方法,以赋予波纹几何形状。波纹增强扭结阻力在弯曲期间,通过膨胀和折叠褶皱,以防止椭圆形和随后的屈曲。波纹状移植物明显改善了抗扭结能力,扭结半径与临床使用的合成移植物相似。与之前的文献相比,波纹状移植物的顺应性值在动脉值范围内(10.4%/mmHg × 10−2±0.3%/mmHg × 10−2),改善了移植物-动脉顺应性匹配。采用柔度有限元模型分析了波纹几何形状对接枝柔度的影响。fe预测的柔度值与实验结果吻合较好,并表明波纹谷的拉格朗日应变幅值的增加与较高的管腔柔度相关。为了确保波形移植物的临床应用,我们测试了候选移植物在生理负荷下的缝线保持强度、破裂压力和稳定性。波纹状移植物保留的生物力学性能高于或类似于隐静脉的报道值,证明了植入的适用性。最后,在脉动流下30天后,接枝尺寸没有显著变化,表明了制作后波纹几何形状的稳定性。具有这种独特生物力学特性的小直径血管移植物有可能改善冠状动脉旁路移植术的长期预后。
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引用次数: 0
Multifunctional Characteristics of Cu/Zn Co-Doped Hydroxyapatite: Enhanced Electrical, Surface, and Biocompatibility Cu/Zn共掺杂羟基磷灰石的多功能特性:增强电、表面和生物相容性
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-15 DOI: 10.1002/jbm.a.37976
M. Durga Ganesh, Mukesh Kumar Manickasamy, P. Joel, Dasari Kalyani, Ajaikumar B. Kunnumakkara, Pamu Dobbidi

Developing multifunctional biomaterials with both electrical and biological properties is crucial for next-generation biomedical platforms. This study looks into how Cu/Zn co-doping affects the structural, electrical, and biological performance of hydroxyapatite (Ca10-x-yZnxCuy(PO4)6(OH)2; x = y = 0.2–1.2), which was synthesized through a solid-state reaction. Among the samples, the CZ6 composition (x = y = 0.6) showed the best properties. It had a single-phase hexagonal structure, a nanoscale crystallite size of about 32 nm, a d-spacing of 0.27 nm along the (112) plane, and a grain size that ranged from 300 to 1200 nm while still keeping the proper composition. Electrical tests showed that CZ6 had the highest dielectric constant of 14.06 at 1 MHz. It maintained a low and stable loss tangent (~0.01), lower grain boundary resistance, and improved AC conductivity (from 10−7 to 10−6 S/cm), indicating better charge transport. These electrical enhancements correlate strongly with improved biological responses. CZ6 displayed strong apatite formation in simulated body fluid, the highest BSA protein adsorption of 25.05 μg/mL, and an optimized zeta potential of −30.54 mV, which facilitates enhanced biomolecular interactions. Cytocompatibility tests with PSVK-1 (skin keratinocytes) and Wi-38 (lung fibroblasts) confirmed that cell viability remained high at all concentrations. While higher levels of dopants led to the formation of secondary phases and diminished biological responses, CZ6 kept a good balance between electroactivity and biofunctionality. These findings make CZ6 a promising electroactive bioceramic for bone tissue engineering, smart implant coatings, and bioelectret scaffolds, where combining electrical responsiveness with cellular compatibility is important.

开发具有电学和生物学特性的多功能生物材料对于下一代生物医学平台至关重要。本研究着眼于Cu/Zn共掺杂如何影响羟基磷灰石(Ca10-x-yZnxCuy(PO4)6(OH)2)的结构、电学和生物学性能;X = y = 0.2-1.2),通过固相反应合成。其中,CZ6组分(x = y = 0.6)的性能最好。它具有单相六方结构,纳米级晶粒尺寸约为32 nm,沿(112)平面的d-间距为0.27 nm,晶粒尺寸在300 ~ 1200 nm之间,但仍保持适当的成分。电学试验表明,在1 MHz时,CZ6的介电常数最高,为14.06。该材料具有较低且稳定的正切损耗(~0.01)、较低的晶界电阻和较高的交流电导率(从10−7 S/cm提高到10−6 S/cm),表明其具有较好的电荷输运性能。这些电增强与生物反应的改善密切相关。CZ6在模拟体液中具有较强的磷灰石形成能力,对BSA蛋白的最高吸附量为25.05 μg/mL, zeta电位为- 30.54 mV,有利于增强生物分子相互作用。PSVK-1(皮肤角质形成细胞)和Wi-38(肺成纤维细胞)的细胞相容性试验证实,在所有浓度下,细胞活力都保持在较高水平。虽然较高的掺杂水平会导致二次相的形成和生物反应的减弱,但CZ6在电活性和生物功能之间保持了良好的平衡。这些发现使CZ6成为一种很有前途的电活性生物陶瓷,可用于骨组织工程、智能植入涂层和生物驻极体支架,在这些领域,结合电响应性和细胞相容性是很重要的。
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引用次数: 0
Fish Collagen-Based Bilayer Composite Scaffold Functionalized With Fibrin/Hydroxyapatite/Sodium Citrate for Osteochondral Tissue Engineering—In Vitro and In Vivo Studies 纤维蛋白/羟基磷灰石/柠檬酸钠功能化鱼胶原双层复合支架用于骨软骨组织工程的体外和体内研究
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-14 DOI: 10.1002/jbm.a.37977
Ashwathi Vijayalekha, Suresh Kumar Anandasadagopan, Thiyagarajan Gopal, Saravanan Durai, Vandhana Anumaiya, Ashok Kumar Pandurangan

Osteochondral defects (OCDs) present significant clinical challenges, necessitating scaffolds that effectively regenerate both cartilage and subchondral bone. We developed a bilayer scaffold using fish collagen extracted from Catla catla skin to overcome the limitations of conventional biomaterials, such as mammalian collagen and synthetic polymers, which often suffer from immunogenic risks, poor bioactivity, or inadequate structural integration. The scaffold is comprised of collagen/fibrin (CC/FIB) for the articular cartilage layer and collagen/sodium citrate/hydroxyapatite (CC/NAC/HAP) for the subchondral bone layer, which is cross-linked with citric acid. Physicochemical characterization confirmed scaffold integration, enhanced thermal stability, and a porous architecture. The scaffold demonstrated optimal porosity (63.12%), degradation (62.08% over 28 days), superior swelling potential, and enhanced bio-mineralization in simulated body fluid. In vitro studies using MG-63 osteoblast-like cells and MC3T3-E1 cells showed high biocompatibility, increased alkaline phosphatase activity, and enhanced calcium deposition (33.73 ± 0.53 μg/mg of protein at 21 days). Gene expression analysis revealed upregulation of osteogenic (COL I ~23-fold, RUNX-2 ~15-fold, OCN ~8-fold) and chondrogenic (COL II ~12-fold, SOX-9 ~10-fold, ACAN ~6-fold) markers, confirming osteochondral regeneration potential. In vivo studies involving the implantation of 3 mm femoral trochlear OCDs in albino Wistar rats (n = 3 per group) resulted in substantial bone and cartilage regeneration, with complete defect closure by 12 weeks. Radiographic and histological assessments at 4, 8, and 12 weeks confirmed well-organized osteochondral repair, demonstrating superior regenerative capability compared to control groups. This study establishes the novelty of the fish collagen-based bilayer scaffold as a promising candidate for osteochondral tissue engineering, supporting effective cartilage and subchondral bone regeneration in OCD treatment.

骨软骨缺损(OCDs)提出了重大的临床挑战,需要有效再生软骨和软骨下骨的支架。我们利用从鲶鱼皮肤中提取的鱼类胶原蛋白开发了一种双层支架,以克服传统生物材料(如哺乳动物胶原蛋白和合成聚合物)经常存在免疫原性风险、生物活性差或结构整合不足的局限性。该支架由胶原/纤维蛋白(CC/FIB)构成关节软骨层,胶原/柠檬酸钠/羟基磷灰石(CC/NAC/HAP)构成软骨下骨层,并与柠檬酸交联。物理化学表征证实支架集成,增强热稳定性和多孔结构。该支架具有最佳的孔隙率(63.12%)、可降解性(28天内可降解62.08%)、优越的膨胀电位以及在模拟体液中增强的生物矿化。mg -63成骨样细胞和MC3T3-E1细胞的体外研究显示出较高的生物相容性,碱性磷酸酶活性增加,钙沉积增强(21 d时33.73±0.53 μg/mg蛋白)。基因表达分析显示,成骨标志物(COL I ~23倍,RUNX-2 ~15倍,OCN ~8倍)和软骨标志物(COL II ~12倍,sox ~10倍,ACAN ~6倍)上调,证实了骨软骨再生潜力。在体内研究中,在白化Wistar大鼠中植入3mm股骨滑车ocd(每组n = 3),导致大量骨和软骨再生,缺损在12周内完全闭合。4周、8周和12周的影像学和组织学评估证实骨软骨修复组织良好,与对照组相比显示出优越的再生能力。本研究建立了基于鱼胶原蛋白的双层支架作为骨软骨组织工程的一个有希望的候选材料,在强迫症治疗中支持有效的软骨和软骨下骨再生。
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引用次数: 0
Development and Characterization of Hyaluronic Acid Microgels for Neural Regeneration Applications 神经再生用透明质酸微凝胶的研制与表征
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-11 DOI: 10.1002/jbm.a.37972
Kassondra N. Hickey, Shannon M. Grassi, George R. Bjorklund, Fallon M. Fumasi, Jaimeson Veldhuizen, Amanda M. Witten, Mehdi Nikkhah, Julianne L. Holloway, Sarah E. Stabenfeldt

Delivery of therapeutic compounds via biomaterial systems has shown promise for tissue regeneration following central nervous system (CNS) injuries. Stromal cell-derived factor-1a (SDF-1a) modulates progenitor cell recruitment to neural injury sites and may contribute to neural repair. However, SDF-1a has a short half-life and requires a delivery system to both protect and sustain its release. Here, we sought to develop a drug delivery platform capable of releasing SDF-1a in a controlled fashion while minimizing inflammation. We used modified hyaluronic acid and microfluidics to generate monodisperse microgels. Characterization of these microgels included size, tunability, degradation, and controlled release properties. Finally, we delivered SDF-1a-loaded microgels to a mouse model of traumatic brain injury at 7 days post-injury and assessed their impact on neural progenitor cell recruitment and astrogliosis. The microfluidic system generated highly monodisperse microgels that successfully encapsulated a matrix metalloproteinase (MMP)-cleavable SDF-1a peptide and retained sensitivity to collagenase. Following intracortical injections, the microgels did not exacerbate the astrocytic response compared to saline injections; no significant difference was observed in neural progenitor cell migration patterns compared to controls. Therefore, we developed a biocompatible microgel system that is highly adaptable for biological delivery and may be utilized in brain/neural applications without exacerbating neuroinflammation.

通过生物材料系统递送治疗性化合物已显示出中枢神经系统(CNS)损伤后组织再生的希望。基质细胞衍生因子-1a (SDF-1a)调节祖细胞向神经损伤部位的募集,并可能有助于神经修复。然而,SDF-1a的半衰期很短,需要一个输送系统来保护和维持其释放。在这里,我们试图开发一种能够以受控方式释放SDF-1a的药物传递平台,同时最大限度地减少炎症。我们使用修饰透明质酸和微流体制备单分散微凝胶。这些微凝胶的表征包括大小、可调性、降解和控释特性。最后,我们在损伤后7天将装载sdf -1a的微凝胶输送到创伤性脑损伤小鼠模型中,并评估其对神经祖细胞募集和星形胶质细胞形成的影响。微流体系统生成了高度单分散的微凝胶,成功地包裹了基质金属蛋白酶(MMP)可切割的SDF-1a肽,并保持了对胶原酶的敏感性。在皮质内注射后,与生理盐水注射相比,微凝胶没有加剧星形细胞反应;与对照组相比,未观察到神经祖细胞迁移模式的显著差异。因此,我们开发了一种生物相容性微凝胶系统,它具有高度的生物递送适应性,可用于脑/神经应用,而不会加剧神经炎症。
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引用次数: 0
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