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Corrigendum to “2D Nanosilicate for additive manufacturing: Rheological modifier, sacrificial ink and support bath Bioprinting” [Bioprinting 25 (2022) e00187] “用于增材制造的二维纳米硅酸盐:流变改性剂、牺牲油墨和支撑浴生物打印”的勘误表[Bioprinting 25 (2022) e00187]
Q1 Computer Science Pub Date : 2025-04-25 DOI: 10.1016/j.bprint.2025.e00417
Satyam Rajput , Kaivalya A. Deo , Tanmay Mathur , Giriraj Lokhande , Kanwar Abhay Singh , Yuxiang Sun , Daniel L. Alge , Abhishek Jain , Tapasree Roy Sarkar , Akhilesh K. Gaharwar
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引用次数: 0
MSLASpheroidStamp: 3d cell spheroids for everyone MSLASpheroidStamp:每个人的3d细胞球体
Q1 Computer Science Pub Date : 2025-04-19 DOI: 10.1016/j.bprint.2025.e00416
A. Minin , T. Semerikova , A.V. Belousova , O. Karavashkova , V. Pozdina , M. Tomilina , I. Zubarev
3D cell cultures, such as cell spheroids, are actively used in biology for modeling biological processes, studying intercellular interactions, and screening pharmacological compounds and are becoming indispensable objects in cell culture laboratories. There are many methods for producing spheroids, which vary in cost and convenience. One of the most convenient and affordable methods is the use of agarose microwells. We developed approaches to fabricate agarose microwells in standard culture plastic with the assistance of a hobby-grade MSLA 3D printer. The use of 3D printing allows the customization of microwells in a wide range of shapes and sizes and scales the production process from a few spheroids to tens of thousands. We have shown that it is possible to create gel microwells in a dish with a glass bottom, which allows us to easily realize time-lapse confocal microscopy of spheroids as well as in situ optical clearing in the same dishes to study the spheroid structure. We demonstrated the ability to study the cytotoxicity of various substances and nanoparticles in commonly used 96-well plates.
Finally, in this article, we describe the difficulties and limitations of our approach and suggest ways to solve them, allowing the reader not only to reproduce it, but also to adapt it to the specific needs of a certain laboratory, using the provided 3D models and instructions.
三维细胞培养,如细胞球体,在生物学中被积极用于模拟生物过程,研究细胞间相互作用,筛选药理化合物,并成为细胞培养实验室不可或缺的对象。生产球体的方法有很多种,其成本和方便性各不相同。琼脂糖微孔是最方便、最经济的方法之一。我们开发了在业余级MSLA 3D打印机的帮助下在标准培养塑料中制造琼脂糖微孔的方法。使用3D打印技术可以定制各种形状和尺寸的微孔,并将生产过程从几个球体扩展到数万个球体。我们已经证明,在一个玻璃底的盘子里制造凝胶微孔是可能的,这使得我们可以很容易地实现球体的延时共聚焦显微镜,以及在同一个盘子里原位光学清除来研究球体结构。我们展示了在常用的96孔板上研究各种物质和纳米颗粒的细胞毒性的能力。最后,在本文中,我们描述了我们的方法的困难和局限性,并提出了解决这些问题的方法,允许读者不仅可以复制它,而且可以使用提供的3D模型和说明使其适应特定实验室的特定需求。
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引用次数: 0
Stimuli-responsive smart materials: Bridging the gap between biotechnology and regenerative medicine 刺激反应智能材料:弥合生物技术和再生医学之间的差距
Q1 Computer Science Pub Date : 2025-04-15 DOI: 10.1016/j.bprint.2025.e00415
Karthik K. Karunakar , Binoy Varghese Cheriyan , Ragavendran Anandakumar , Akshaya Murugathirumal , Abinaya Senthilkumar , J. Nandhini , Kunal Kataria , Lincy Yabase
Stimuli-responsive smart materials have emerged as transformative tools at the interface of biotechnology and regenerative medicine. These materials, capable of responding dynamically to diverse physical, chemical, and biological stimuli, present innovative solutions to longstanding challenges in tissue engineering, drug delivery, and wound healing. This review covers the main principles of stimuli-responsive materials, their classifications, and underlying mechanisms of response. The emphasis lies on the central role that smart materials play in the advancement of biomedical applications. The versatility and functional adaptability of key categories of smart materials, such as polymers, hydrogels, and nanostructures, are reviewed for their utility in therapeutic applications. With an eye on smart scaffolds, controlled drug delivery systems, and new wound healing techniques, we also go over their uses in tissue engineering. Emerging technologies such as 3D/4D bioprinting, microfluidic fabrication, and the incorporation of biosensors, artificial intelligence (AI), and the Internet of Things (IoT) into the design and development of smart materials are also covered. The review will clearly establish that stimuli-responsive smart materials have boundless potential for transformative usefulness in regenerative medicine and health futures by highlighting key concerns, particularly those related to scalability and the regulatory landscape.
刺激响应智能材料已经成为生物技术和再生医学领域的变革性工具。这些材料能够对各种物理、化学和生物刺激做出动态反应,为组织工程、药物输送和伤口愈合方面的长期挑战提供了创新的解决方案。本文综述了刺激反应物质的主要原理、分类以及刺激反应的基本机制。重点在于智能材料在生物医学应用的进步中发挥的核心作用。主要类别的智能材料,如聚合物、水凝胶和纳米结构的多功能性和功能适应性,综述了它们在治疗应用中的用途。着眼于智能支架,控制药物输送系统,以及新的伤口愈合技术,我们也将讨论它们在组织工程中的应用。新兴技术,如3D/4D生物打印,微流体制造,以及生物传感器,人工智能(AI)和物联网(IoT)纳入智能材料的设计和开发也被涵盖。通过强调关键问题,特别是与可扩展性和监管环境相关的问题,该综述将清楚地确定,刺激响应型智能材料在再生医学和健康未来方面具有无限的变革性用途潜力。
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引用次数: 0
3D Printing β-TCP-laden GelMA/Alginate interpenetrating-polymer-network biomaterial inks for bone tissue engineering 用于骨组织工程的3D打印β- tcp负载GelMA/海藻酸盐互穿聚合物网络生物材料墨水
Q1 Computer Science Pub Date : 2025-04-14 DOI: 10.1016/j.bprint.2025.e00413
Joyce R. de Souza , Maedeh Rahimnejad , Igor P. Mendes Soares , Caroline Anselmi , Pedro H.C. de Oliveira , Alexandre H. dos Reis-Prado , Victoria Maglaras , Renan Dal-Fabbro , Eliandra S. Trichês , Marco C. Bottino
Bone's capacity for self-repair is limited when large defects arise from trauma or infection. Traditional grafting methods like autografts and allografts often face challenges like immune rejection and limited availability. Traditional scaffold manufacturing techniques for bone tissue engineering frequently lack precise control over the constructs' material composition and pore architecture. Recently, 3D printing technology, particularly with interpenetrating polymer networks (IPNs), has successfully addressed these limitations, improving biocompatibility, strength, and degradation. Our study investigated gelatin methacryloyl (GelMA)/Alginate IPNs laden with beta tri-calcium phosphate (β-TCP) particles in a 3D-printed format to optimize cell proliferation and tissue regeneration conditions. Rheology studies showed shear-thinning viscosity and fast recovery (∼90 %) to primary viscosity after stress removal, confirming the inks' suitability for extrusion-based printing. Both inks demonstrated high resolution and acceptable printability (0.9–1). Incorporating β-TCP increased the compressive modulus (0.09 ± 0.01 MPa for the control group vs. 0.15 ± 0.01 MPa for 15 % (w/v) β-TCP, ∗∗∗p < 0.001) and swelling ratio, decreasing biodegradation over 35 days. Cell assays showed enhanced cell proliferation over 7 days, with no significant differences between groups. Compared to basal and osteogenic media controls, higher mineralization and osteogenic gene expression were observed in 15 % β-TCP-laden 3D-printed constructs on days 14 and 21. Histological analysis in vivo showed no signs of inflammation after three weeks, suggesting favorable tissue compatibility. Furthermore, calcium carbonate deposits were identified, evidencing the successful differentiation of mesenchymal stem cells into cells capable of producing a mineralized matrix. This study demonstrated that the (GelMA)/Alginate IPN containing β-TCP could be a successful biomaterial ink with promising bioactive properties for bone tissue engineering.
当创伤或感染造成大面积缺损时,骨骼的自我修复能力就会受到限制。自体移植物和异体移植物等传统移植方法往往面临免疫排斥和供应有限等挑战。用于骨组织工程的传统支架制造技术往往无法精确控制构建物的材料成分和孔隙结构。最近,三维打印技术,尤其是互穿聚合物网络(IPN),成功地解决了这些局限性,改善了生物相容性、强度和降解性。我们的研究以三维打印的形式研究了含有β-磷酸三钙(β-TCP)颗粒的明胶甲基丙烯酰(GelMA)/海藻酸盐 IPN,以优化细胞增殖和组织再生条件。流变学研究显示了剪切稀化粘度和去除应力后快速恢复(90%)的原始粘度,这证实了油墨适用于基于挤压的打印。两种油墨都具有高分辨率和可接受的印刷适性(0.9-1)。加入 β-TCP 增加了压缩模量(对照组为 0.09 ± 0.01 MPa,15 %(w/v)β-TCP 为 0.15 ± 0.01 MPa,∗∗∗p < 0.001)和膨胀率,减少了 35 天内的生物降解。细胞检测显示,7 天内细胞增殖增强,组间无显著差异。与基础培养基和成骨培养基对照组相比,15% β-TCP 加载的三维打印构建体在第 14 天和第 21 天的矿化度和成骨基因表达更高。体内组织学分析表明,三周后无炎症迹象,表明组织相容性良好。此外,还发现了碳酸钙沉积物,证明间充质干细胞成功分化为能够产生矿化基质的细胞。这项研究表明,含有β-TCP的(GelMA)/海藻酸盐IPN是一种成功的生物材料墨水,具有良好的生物活性,可用于骨组织工程。
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引用次数: 0
Characteristics and osteogenic potential of scaffolds with controlled pore geometry obtained by FDM 3D printing technology from resorbable bioplastics 利用可吸收生物塑料的 FDM 3D 打印技术获得的具有可控孔隙几何形状的支架的特性和成骨潜力
Q1 Computer Science Pub Date : 2025-04-12 DOI: 10.1016/j.bprint.2025.e00414
Galina A. Ryltseva , Alexey E. Dudaev , Sergei Y. Lipaikin , Konstantin A. Kistersky , Ekaterina I. Shishatskaya , Tatiana G. Volova
In the field of tissue engineering, the architecture of a scaffold plays a critical role in determining how cells behave and how new tissue structures are formed. In this study, we have for the first time developed and compared four different types of 3D printed scaffolds made from biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate). These scaffolds varied in terms of their internal channel topologies, which included triangular, square, and hexagonal geometry, as well as a configuration based on the Hilbert curve. The scaffolds were fabricated via the process of 3D printing using the method of fused deposition modeling, based on pre-designed computer models. The investigation into the proliferation, metabolic activity, and osteogenic differentiation of human mesenchymal stem cells (MSCs) revealed a substantial impact of scaffold architecture on the dynamics of channel closure. Initially, MSCs tended to adhere and proliferate in regions of high curvature, such as corners of triangular channels or bends of the Hilbert curve-shaped channels. The cells on the scaffolds with a triangular structure of pores exhibited a higher level of metabolic activity and a faster rate of channel closure compared to other structures. At the later stages of cultivation, all types of channels were fully colonized by cells, with no indication of a decrease in metabolic activity. Analysis of osteogenic differentiation revealed that all scaffolds facilitate the differentiation of MSCs into osteoblasts; however, on day 14 of cultivation, slightly lower alkaline phosphatase activity was observed on scaffolds with square-shaped channels. On day 28 of cultivation, the scaffolds with the Hilbert curve geometry of channels demonstrated the highest degree of mineralization. Our research is a step forward in the exploration of the design and 3D printing of polyhydroxyalkanoate-based scaffolds with different cell-stimulating geometries for restoration of critical-size bone defects. This research contributes to the development of innovative functional materials.
在组织工程领域,支架的结构在决定细胞如何行为和新组织结构如何形成方面起着关键作用。在这项研究中,我们首次开发并比较了四种不同类型的由可生物降解聚合物聚(3-羟基丁酸酯-co-3-羟基戊酸酯)制成的3D打印支架。这些支架的内部通道拓扑结构各不相同,包括三角形、正方形和六边形几何形状,以及基于希尔伯特曲线的配置。基于预先设计的计算机模型,采用熔融沉积建模的方法通过3D打印工艺制造支架。对人间充质干细胞(MSCs)的增殖、代谢活性和成骨分化的研究揭示了支架结构对通道关闭动力学的重大影响。最初,间质干细胞倾向于在高曲率区域粘附和增殖,如三角形通道的角落或希尔伯特曲线形状通道的弯曲处。与其他结构的细胞相比,具有三角形孔结构的支架细胞表现出更高的代谢活性和更快的通道关闭速度。在培养后期,所有类型的通道都被细胞完全定植,没有代谢活性下降的迹象。成骨分化分析表明,所有支架均能促进间充质干细胞向成骨细胞分化;但在培养第14天,方形通道支架的碱性磷酸酶活性略低。培养第28天,通道呈Hilbert曲线的支架矿化程度最高。我们的研究是探索设计和3D打印具有不同细胞刺激几何形状的聚羟基烷酸酯基支架的一步,用于修复临界尺寸的骨缺陷。这项研究有助于创新功能材料的发展。
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引用次数: 0
Reproducing viscoelastic properties of soft tissues in 3D printed silicone models by two-phase infill tuning 采用两相填充调谐技术在3D打印硅胶模型中再现软组织的粘弹性特性
Q1 Computer Science Pub Date : 2025-04-05 DOI: 10.1016/j.bprint.2025.e00408
Stephan Dehen , Felix Groß , Andrea Lorenz , Dieter H. Pahr , Andreas G. Reisinger
Anatomical models are essential tools for teaching, patient education, or training. Recent developments in 3D printing enabled the production of customised models based on individual imaging data. Although most 3D printing processes can accurately reproduce anatomical structures geometrically, they lack similarity in haptic properties. Therefore, in this study, we investigated the influence of highly viscous silicone oil injections in 3D printed silicone samples on enhancing viscoelastic behaviour. For this, 72 specimens with 3 different infill densities (20 %, 30 %, 40 %) were printed and tested using stress relaxation tests. Afterwards, they were filled using 3 different high viscous silicone oils (1 kPas, 5 kPas, 10 kPas) and retested. The material properties of the silicone infill/silicone oil combination were extracted from the structural properties of the tested samples using an optimisation strategy based on a finite element model to get the material response for the infill only. Alongside the infill density, the storage modulus increases from 28.0 to 52.3 kPa for empty samples. By adding high viscous silicone oil the loss modulus is increased from 3.3–5.6 kPa up to 12.0–20.0 kPa. The resulting loss tangent increases from 0.10–0.12 to 0.28–0.29 for the different infill densities. With this range of possible viscoelastic properties, several different biological soft tissues can be modelled. It could be proven that a silicone oil injection is a promising way to increase the loss moduli of 3D printed silicone samples, greatly increasing the design space of possible printable viscoelastic properties.
解剖模型是教学、患者教育或培训必不可少的工具。3D打印的最新发展使基于个人成像数据的定制模型的生产成为可能。虽然大多数3D打印工艺可以在几何上精确地复制解剖结构,但它们在触觉特性上缺乏相似性。因此,在本研究中,我们研究了在3D打印硅胶样品中注射高粘性硅油对增强粘弹性行为的影响。为此,打印了72个具有3种不同填充密度(20%,30%,40%)的试件,并使用应力松弛试验进行了测试。然后,用3种不同的高粘性硅油(1 kPa⋅s、5 kPa⋅s、10 kPa⋅s)填充并重新测试。利用基于有限元模型的优化策略,从测试样品的结构特性中提取有机硅填充物/硅油组合的材料特性,以获得仅对填充物的材料响应。随着填充密度的增加,空样品的存储模量从28.0增加到52.3 kPa。加入高粘性硅油后,损失模量由3.3 ~ 5.6 kPa提高到12.0 ~ 20.0 kPa。对于不同的充填密度,损失切线从0.10-0.12增加到0.28-0.29。有了这种可能的粘弹性特性,几种不同的生物软组织可以建模。可以证明,注入硅油是一种很有前途的方法,可以增加3D打印硅胶样品的损失模量,大大增加了可能打印的粘弹性性能的设计空间。
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引用次数: 0
Cryopreservation of vascularizable tissue with temperature-controlled-cryoprinting 用温度控制的冷冻打印技术冷冻保存可血管组织
Q1 Computer Science Pub Date : 2025-04-02 DOI: 10.1016/j.bprint.2025.e00411
Linnea Warburton , Angie Cheng , Boris Rubinsky
Advancements in regenerative medicine have made it possible to fabricate complex, engineered tissues which closely mimic in vivo tissue. As with in vivo tissue, vascularization is crucial for supplying cells in the engineered tissue with nutrients. However, cryopreserving engineered tissues remains challenging due to their large 3D volume. Without effective cryopreservation techniques, it is difficult to use vascularized tissues at scale for drug development or to create banks for patient transplantation. Previously, our group developed Temperature-Controlled-Cryoprinting as a novel technology for simultaneously fabricating and cryopreserving 3D bioprinted tissue. During Temperature-Controlled-Cryoprinting, a cell-laden bioink is printed and frozen layer-by-layer under optimal cooling rates. In this study, we demonstrate that this approach can be used to cryopreserve the cell types which are most sensitive to cryopreservation: primary cells and stem cells. Human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were encapsulated in a collagen bioink and cryoprinted. The tissues were stored at −80 °C, and then thawed at 37 °C. After thawing, the HUVECs and hMSCs naturally self-assembled into hollow capillaries, creating vascularized tissue. Analysis with Fiji found that vascular network formation was not impeded by cryopreservation and resembled that of a non-cryopreserved tissue. The ability to cryopreserve vascularizable tissue is an important advance, as it allows these tissues to become a shelf-stable product that can be shipped or stored long-term.
再生医学的进步使得制造复杂的、近似活体组织的工程组织成为可能。与体内组织一样,血管化对于为工程组织中的细胞提供营养至关重要。然而,由于工程组织的三维体积较大,低温保存工程组织仍然具有挑战性。如果没有有效的低温保存技术,就很难将血管化组织大规模地用于药物开发或建立患者移植库。此前,我们的研究小组开发了温控冷冻打印技术(Temperature-Controlled-Cryoprinting),作为同时制造和冷冻保存三维生物打印组织的新技术。在温控冷冻打印过程中,含有细胞的生物墨水逐层打印并在最佳冷却速率下冷冻。在这项研究中,我们证明了这种方法可用于低温保存对低温保存最敏感的细胞类型:原代细胞和干细胞。我们将人脐静脉内皮细胞(HUVECs)和人间充质干细胞(hMSCs)包裹在胶原蛋白生物墨水中并进行了低温打印。组织在-80 °C下保存,然后在37 °C下解冻。解冻后,HUVECs 和 hMSCs 自然自组装成空心毛细血管,形成血管化组织。利用 Fiji 进行的分析发现,血管网络的形成不受冷冻保存的阻碍,与未冷冻保存的组织相似。低温保存血管化组织的能力是一项重要的进步,因为它使这些组织成为一种可长期运输或储存的货架稳定产品。
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引用次数: 0
3D printed osteoporotic bone model validated in dynamic culture 3D打印骨质疏松症骨模型在动态培养中得到验证
Q1 Computer Science Pub Date : 2025-04-02 DOI: 10.1016/j.bprint.2025.e00410
Elisa Batoni , Nikoleta N. Tavernaraki , Varvara Platania , Carmelo De Maria , Maria Chatzinikolaidou , Giovanni Vozzi
Osteoporosis is a worldwide bone disease characterized by reduced bone mass and an alteration of bone architecture, leading to bone fragility and an increased risk of fractures. Although animal models are still the gold standard for studying and testing new anti-osteoporotic drugs, they are expensive and unable to reproduce the in vivo conditions accurately, thus making their replacement with alternative methods an urgent need. In the field of bone tissue engineering, pathological three-dimensional (3D) in vitro bone models have been recently considered to overcome economic and ethical issues associated with traditional pre-clinical testing methods. As a result, this study aimed to design a 3D in vitro model of osteoporotic bone consisting of 3D printed scaffolds that resemble the architectural and bone mineral content differences between physiological and osteoporotic bone, and pre-osteoblastic cells seeded onto the scaffolds. A physiological 3D in vitro bone model was designed and printed as a control condition. A comprehensive physicochemical characterization of unseeded scaffolds was conducted in terms of mechanical and thermal properties, swelling behaviour, degradation, and morphology examination under scanning electron microscopy. Cell-seeded physiological and osteoporotic bone scaffolds were cultured under mechanical stimulation to mimic the mechanical forces experienced daily by human bones. The application of mechanical stimuli had a significantly positive effect on the osteogenic differentiation of the pre-osteoblastic cells, with cell-seeded osteoporotic scaffolds reporting the lowest values, thus resembling the reduction in bone formation in osteoporotic patients.
骨质疏松症是一种世界性的骨病,其特征是骨量减少和骨结构改变,导致骨脆性和骨折风险增加。尽管动物模型仍然是研究和测试新型抗骨质疏松药物的金标准,但动物模型价格昂贵且无法准确再现体内条件,因此迫切需要用替代方法替代动物模型。在骨组织工程领域,病理三维(3D)体外骨模型最近被认为克服了与传统临床前测试方法相关的经济和伦理问题。因此,本研究旨在设计一个骨质疏松性骨的3D体外模型,该模型由3D打印支架组成,该支架与生理性骨和骨质疏松性骨的结构和骨矿物质含量差异相似,并将成骨前细胞植入支架上。设计并打印体外生理三维骨模型作为对照条件。在扫描电镜下对未播种的支架进行了全面的物理化学表征,包括机械和热性能、膨胀行为、降解和形态学检查。在机械刺激下培养细胞种子生理性和骨质疏松性骨支架,以模拟人类骨骼日常承受的机械力。机械刺激的应用对成骨前细胞的成骨分化有显著的积极影响,其中细胞种子的骨质疏松支架的成骨分化值最低,因此类似于骨质疏松患者骨形成的减少。
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引用次数: 0
Topology optimization and manufacturing of maxillofacial patient specific implant using FEA and AM 基于有限元分析和AM技术的颌面部患者特异性种植体拓扑优化与制造
Q1 Computer Science Pub Date : 2025-04-02 DOI: 10.1016/j.bprint.2025.e00412
Rakesh Koppunur , K. Ramakrishna , A. Manmadhachary , Dama Kiran Kumar , V. Sridhar
Patient-specific implants have gained significant attention due to their adaptability and precision in addressing individual anatomical variations. However, optimizing the strength-to-weight ratio remains a critical design challenge. This study focuses on the analysis and topological optimization of patient-specific implants to enhance their mechanical performance while minimizing weight. Finite Element Analysis (FEA) is employed to evaluate the maximum mastication force that a maxillofacial implant can withstand, ensuring that stress distribution and deformation remain within acceptable limits. Given the crucial role of mastication forces in implant stability and longevity, design iterations are conducted to achieve an improved strength-to-weight ratio. The optimized design undergoes validation through FEA under identical boundary and loading conditions. Results indicate a 4.43 % reduction in implant weight with a marginal 4 μm increase in deformation compared to the non-optimized design. To manufacture the optimized implant with high precision and structural integrity, Direct Metal Laser Sintering (DMLS), an advanced Additive Manufacturing (AM) technique, is utilized. This approach enables the fabrication of complex geometries while maintaining superior mechanical properties, ensuring the feasibility of the optimized implant for clinical applications.
患者特异性植入物由于其在解决个体解剖变异方面的适应性和精确性而获得了极大的关注。然而,优化强度重量比仍然是一个关键的设计挑战。本研究的重点是对患者特异性植入物的分析和拓扑优化,以提高其机械性能,同时最小化重量。采用有限元分析(FEA)评估颌面种植体所能承受的最大咀嚼力,确保应力分布和变形保持在可接受的范围内。考虑到咀嚼力对种植体稳定性和寿命的关键作用,设计迭代进行,以实现改进的强度重量比。在相同的边界和载荷条件下,通过有限元分析对优化设计进行了验证。结果表明,与非优化设计相比,植入物重量减少了4.43%,变形增加了4 μm。为了制造高精度和结构完整的优化种植体,使用了直接金属激光烧结(DMLS),一种先进的增材制造(AM)技术。这种方法可以制造复杂的几何形状,同时保持优越的机械性能,确保优化的植入物在临床应用中的可行性。
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引用次数: 0
Three-dimensional meltblowing as a high-speed fabrication process for tendon tissue engineered scaffolds 三维熔喷法制备肌腱组织工程支架
Q1 Computer Science Pub Date : 2025-03-28 DOI: 10.1016/j.bprint.2025.e00409
Kentaro Umemori , Benham Pourdeyhimi , Dianne Little
Rotator cuff tears continue to be a critical challenge for successful repair due to the formation of fibrotic scar tissue during healing. Tendon tissue engineering seeks to improve these outcomes using nonwoven fabrication methods to produce biomimetic scaffolds. Meltblowing has several advantages over other nonwoven approaches including non-toxic fabrication processes and being high-throughput and economical, while accurately producing fiber diameters comparable to native tendon microstructure. Recently 3D meltblowing (3DMB) introduced high degrees of tunability to the core process, allowing for production of highly aligned fiber mats at anatomically relevant dimensions. Here, we evaluated 3DMB scaffolds fabricated using poly-L-lactic acid (PLA) and poly-ε-caprolactone (PCL) by characterizing scaffold properties before and after culture with human adipose stem cells (hASCs). Mechanical and fiber characterization of 3DMB scaffolds closely resembled tendon microarchitecture by exhibiting high fiber alignment and mechanical anisotropy. hASC-seeded 3DMB scaffolds after 28 days of culture proliferated and deposited aligned tendon-like extracellular matrix. Furthermore, cell culture enhanced the Young's modulus of PLA 3DMB scaffolds and improved yield stress, yield stretch, and stiffness of both 3DMB scaffolds. The proteome of cultured 3DMB scaffolds increased expression of tendon-related proteins after 28 days of culture, but polymer-dependent differences in glycoprotein composition was observed. Together, 3DMB is a promising method for tendon tissue engineering, by showing improved fiber and mechanical properties compared to meltblown scaffolds. However, while an improvement on prior iterations, continued development of this 3DMB technology is needed to better mimic the mechanical properties and biologic composition of native tendon.
由于纤维化瘢痕组织在愈合过程中的形成,肩袖撕裂仍是成功修复的关键挑战。肌腱组织工程学试图利用无纺布制造方法来生产仿生物支架,从而改善这些结果。与其他无纺布方法相比,熔喷技术具有多项优势,包括无毒制造工艺、高通量和经济性,同时还能精确制造出与原生肌腱微观结构相当的纤维直径。最近,三维熔喷(3DMB)为核心工艺引入了高度可调性,可生产出解剖相关尺寸的高度对齐的纤维毡。在此,我们评估了使用聚左旋乳酸(PLA)和聚ε-己内酯(PCL)制作的三维MB支架,在培养人脂肪干细胞(hASCs)前后对支架特性进行了表征。三维MB支架的机械和纤维特性与肌腱的微结构非常相似,表现出高度的纤维排列和机械各向异性。此外,细胞培养还提高了聚乳酸三维MB支架的杨氏模量,改善了两种三维MB支架的屈服应力、屈服拉伸和刚度。培养三维MB支架的蛋白质组在培养28天后增加了肌腱相关蛋白的表达,但观察到糖蛋白组成的差异取决于聚合物。总之,与熔喷支架相比,三维MB具有更好的纤维和机械性能,是一种很有前景的肌腱组织工程方法。不过,虽然三维MB技术比以前的迭代技术有所改进,但仍需继续开发,以更好地模拟原生肌腱的机械性能和生物组成。
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