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Droplet-based bioprinting for fabrication of tumor spheroids 基于液滴的生物打印技术制造肿瘤球体
IF 8.4 3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-01-02 DOI: 10.36922/ijb.1214
Congying Liu, Yuhe Chen, Huawei Chen, Pengfei Zhang
Cancer is now one of the leading causes of mortality worldwide, and the cancer treatment development is still slow due to the lack of efficient in vitro tumor models for studying tumorigenesis and facilitating drug development. Multicellular tumor spheroids can recapitulate the critical properties of tumors in vivo, including spatial organization, physiological responses, and metabolism, and are considered powerful platform for disease study and drug screening. Although several spheroid fabrication methods have been developed, most of them result in uncontrolled cell aggregations, yielding spheroids of variable size and function. Droplet-based bioprinting is capable of depositing cells in spatiotemporal manner so as to control the composition and distribution of printed biological constructs, thereby facilitating high-throughput fabrication of complicated and reproducible tumor spheroids. In this review, we introduce the progress of droplet-based bioprinting technology for the fabrication of tumor spheroids. First, different droplet-based bioprinting technologies are compared in terms of their strengths and shortcomings, which should be taken into account while fabricating tumor spheroids. Second, the latest advances in modeling distinct types of cancers and the enabled applications with tumor spheroids are summarized. Finally, we discuss the challenges and potentials revolving around the advances of bioprinting technology, improvement of spheroid quality, and integration of different technologies.
癌症是目前导致全球死亡的主要原因之一,而由于缺乏研究肿瘤发生和促进药物开发的高效体外肿瘤模型,癌症治疗的发展仍然缓慢。多细胞肿瘤球可以再现体内肿瘤的关键特性,包括空间组织、生理反应和新陈代谢,被认为是疾病研究和药物筛选的强大平台。虽然目前已开发出多种球体制造方法,但大多数方法都会导致细胞聚集失控,产生大小和功能各异的球体。基于液滴的生物打印技术能以时空方式沉积细胞,从而控制打印生物构建体的组成和分布,因此有助于高通量制造复杂且可重复的肿瘤球体。在这篇综述中,我们将介绍基于液滴的生物打印技术在制造肿瘤球体方面的进展。首先,比较了不同液滴生物打印技术的优缺点,这些优缺点是在制作肿瘤球体时应该考虑的。其次,总结了不同类型癌症建模的最新进展以及肿瘤球体的应用。最后,我们讨论了围绕生物打印技术的进步、球形体质量的提高以及不同技术的整合所带来的挑战和潜力。
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引用次数: 0
Microfluidic fiber spinning for 3D bioprinting: Harnessing microchannels to build macrotissues 用于三维生物打印的微流体纤维纺丝:利用微通道构建大组织
IF 8.4 3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-01-02 DOI: 10.36922/ijb.1404
Federico Serpe, C. Casciola, Giancarlo Ruocco, Gianluca Cidonio, C. Scognamiglio
Microfluidics is rapidly revolutionizing the scientific panorama, providing unmatched high-throughput platforms that find application in numerous areas of physics, chemistry, biology, and materials science. Recently, microfluidic chips have been proposed, in combination with bioactive materials, as promising tools for spinning cell-laden fibers with on-demand characteristics. However, cells encapsulated in filaments produced via microfluidic spinning technology are confined in a quasi-three-dimensional (3D) environment that fails to replicate the intricate 3D architecture of biological tissues. Thanks to the recent synergistic combination of microfluidic devices with 3D bioprinting technologies that enable the production of sophisticated microfibers serving as the backbone of 3D structures, a new age of tissue engineering is emerging. This review looks at how combining microfluidics with 3D printing is contributing to the biofabrication of relevant human substitutes and implants. This paper also describes the whole manufacturing process from the production of the microfluidic tool to the printing of tissue models, focusing on cutting-edge fabrication technologies and emphasizing the most noticeable achievements for microfluidic spinning technology. A theoretical insight for thixotropic hydrogels is also proposed to predict the fiber size and shear stress developing within microfluidic channels. The potential of using microfluidic chips as bio-printheads for multi-material and multi-cellular bioprinting is discussed, highlighting the challenges that microfluidic bioprinting still faces in advancing the field of biofabrication for tissue engineering and regenerative medicine purposes.
微流控技术正在迅速革新科学领域,它提供了无与伦比的高通量平台,可应用于物理、化学、生物和材料科学的众多领域。最近,有人提出将微流控芯片与生物活性材料结合起来,作为按需纺制含有细胞的纤维的理想工具。然而,通过微流体纺丝技术生产的纤维丝中包裹的细胞被限制在一个准三维(3D)环境中,无法复制生物组织错综复杂的三维结构。近年来,微流体设备与三维生物打印技术协同结合,生产出作为三维结构骨架的精密微纤维,组织工程的新时代正在到来。本综述探讨了微流控技术与三维打印技术的结合如何促进相关人体替代品和植入物的生物制造。本文还介绍了从生产微流控工具到打印组织模型的整个制造过程,重点关注最前沿的制造技术,并强调了微流控纺丝技术最显著的成就。此外,还提出了触变性水凝胶的理论见解,以预测微流体通道内纤维尺寸和剪切应力的发展。讨论了使用微流控芯片作为生物打印头进行多材料和多细胞生物打印的潜力,强调了微流控生物打印在推进用于组织工程和再生医学的生物制造领域中仍然面临的挑战。
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引用次数: 0
Application of biomaterial-based three-dimensional bioprinting for organ-on-a-chip fabrication 将基于生物材料的三维生物打印技术应用于芯片上器官的制造
IF 8.4 3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-01-02 DOI: 10.36922/ijb.1972
Joeng Ju Kim, Mihyeon Bae, Jongmin Kim, Dong-Woo Cho
An organ-on-a-chip is a microfluidic device that simulates the microenvironment of organs, facilitating the study of human physiology and disease mechanisms. Through the integration of tissue engineering and micromachining technologies, it effectively manages the cellular microenvironment and implements tissue-specific functions and physiological responses with high fidelity. Several factors must be appropriately considered in the fabrication of an organ-on-a-chip, including the choice of biomaterials to simulate the extracellular matrix (ECM), selection of cells constituting the target organ, incorporation of humanized design to realize the primary function and structure of the organ, and the use of appropriate biofabrication methods to build a tissue-specific environment. Notably, three-dimensional (3D) bioprinting has emerged as a promising method for biofabricating organ-on-a-chip. Three-dimensional bioprinting offers versatility in adapting to various biomaterials with different physical properties, allowing precise control of 3D cell arrays and facilitating cyclic movements of fluidic flow within microfluidic platforms. These capabilities enable the precise fabrication of organ-on-a-chip that reflects tissue-specific functions and microenvironments. Additionally, 3D-bioprinted organ-on-a-chip can serve as a disease-on-a-chip platform, achieved through the implementation of pathophysiological environments and integration with devices such as bioreactors. Their significance in pharmacology research lies in their exceptional resemblance to the 3D microenvironment structure of actual organs, which are conducive for the validation of sequential mechanism of drug action. This review describes recent examples of organ-on-a-chip applications for various organs and state-of-the-art 3D bioprinting techniques employed in organ-on-a-chip fabrication. The discussion extends to the future prospects of this technology, encompassing aspects such as commercialization through mass production and its potential application in personalized medicine or drug-screening platforms. Serving as a relevant guide, this review offers insights for future research and developments in in vitro micromodel fabrication.
器官芯片是一种模拟器官微环境的微流控装置,有助于研究人体生理和疾病机制。通过整合组织工程和微机械加工技术,它能有效管理细胞微环境,高保真地实现组织特异功能和生理反应。制造芯片上的器官必须适当考虑几个因素,包括选择生物材料来模拟细胞外基质(ECM)、选择构成目标器官的细胞、结合人性化设计来实现器官的主要功能和结构,以及使用适当的生物制造方法来构建组织特异性环境。值得注意的是,三维(3D)生物打印已成为生物制造片上器官的一种有前途的方法。三维生物打印具有适应各种不同物理性质生物材料的多功能性,可精确控制三维细胞阵列,并促进微流体平台内流体流动的循环运动。有了这些功能,就能精确制造出反映组织特异功能和微环境的芯片器官。此外,三维生物打印器官芯片还可作为疾病芯片平台,通过实施病理生理环境并与生物反应器等设备集成来实现。它们在药理学研究中的意义在于其与实际器官的三维微环境结构极为相似,有利于验证药物作用的顺序机制。本综述介绍了器官芯片应用于各种器官的最新实例,以及器官芯片制造中采用的最先进的三维生物打印技术。讨论延伸到这项技术的未来前景,包括通过大规模生产实现商业化及其在个性化医疗或药物筛选平台中的潜在应用等方面。作为相关指南,本综述为体外微模型制造的未来研究和发展提供了见解。
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引用次数: 0
Three-dimensional bioprinting for musculoskeletal regeneration and disease modeling 用于肌肉骨骼再生和疾病建模的三维生物打印技术
IF 8.4 3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-01-02 DOI: 10.36922/ijb.1037
Qiang Wei, Yuhao Peng, Weicheng Chen, Yudong Duan, Genglei Chua, Jie Hu, Shujun Lyu, Zhigang Chen, F. Han, Bin Li
Musculoskeletal disease and injury are highly prevalent disorders that impose tremendous medical and socioeconomic burdens. Tissue engineering has attracted increasing attention as a promising technique of regenerative medicine to restore degenerative or damaged tissues and is used to produce functional disease models. As a revolutionary technology, three-dimensional (3D) bioprinting has demonstrated a considerable potential in enhancing the versatility of tissue engineering. 3D bioprinting allows for the rapid and accurate spatial patterning of cells, growth factors, and biomaterials to generate biomimetic tissue constructs. Meanwhile, 3D-bioprinted in vitro models also offer a viable option to enable precise pharmacological interventions in various diseases. This review provides an overview of 3D bioprinting methods and bioinks for therapeutic applications and describes their potential for musculoskeletal tissue regeneration. We also highlight the fabrication of 3D-bioprinted models for drug development targeting musculoskeletal disease. Finally, the existing challenges and future perspectives of 3D bioprinting for musculoskeletal regeneration and disease modeling are discussed.
肌肉骨骼疾病和损伤是非常普遍的疾病,给医疗和社会经济造成了巨大负担。组织工程作为一种前景广阔的再生医学技术,在恢复退化或受损组织以及用于制作功能性疾病模型方面吸引了越来越多的关注。作为一项革命性技术,三维(3D)生物打印技术在提高组织工程的多功能性方面展现出了巨大的潜力。三维生物打印可以快速、准确地对细胞、生长因子和生物材料进行空间图案化,从而生成仿生组织结构。同时,三维生物打印体外模型也为对各种疾病进行精确的药物干预提供了可行的选择。本综述概述了用于治疗的三维生物打印方法和生物墨水,并介绍了它们在肌肉骨骼组织再生方面的潜力。我们还重点介绍了三维生物打印模型的制作,用于针对肌肉骨骼疾病的药物开发。最后,讨论了三维生物打印在肌肉骨骼再生和疾病建模方面的现有挑战和未来前景。
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引用次数: 0
Exploring the mechanical strength, antimicrobial performance, and bioactivity of 3D-printed silicon nitride-PEEK composites in cervical spinal cages. 探索3d打印氮化硅- peek复合材料在颈椎笼中的机械强度、抗菌性能和生物活性。
IF 6 3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-01-01 Epub Date: 2024-02-26 DOI: 10.36922/ijb.2124
Cemile Basgul, Paul DeSantis, Tabitha Derr, Noreen J Hickok, Ryan M Bock, Steven M Kurtz

In this study, our goal was to assess the suitability of a polyether-ether-ketone (PEEK) and silicon nitride (Si3N4) polymer composite for antimicrobial three-dimensional (3D)-printed cervical cages. Generic cage designs (PEEK and 15 vol.% Si3N4-PEEK) were 3D-printed, including solid and porous cage designs. Cages were tested in static compression, compression shear, and torsion per ASTM F2077. For antibacterial testing, virgin and composite filament samples were inoculated with Staphylococcus epidermidis and Escherichia coli. In vitro cell testing was conducted using MC3T3-E1 mouse preosteoblasts, where cell proliferation, cumulative mineralization, and osteogenic activity were measured. The 3D-printed PEEK and Si3N4-PEEK cages exhibited adequate mechanical strength for all designs, exceeding 14.7 kN in compression and 6.9 kN in compression shear. Si3N4-PEEK exhibited significantly lower bacterial adhesion levels, with a 93.9% reduction (1.21 log), and enhanced cell proliferation when compared to PEEK. Si3N4-PEEK would allow for custom fabrication of 3D-printed spinal implants that reduce the risk of infection compared to unfilled PEEK or metallic alloys.

在这项研究中,我们的目标是评估聚醚醚酮(PEEK)和氮化硅(Si3N4)聚合物复合材料用于抗菌三维(3D)打印颈椎笼的适用性。通用笼设计(PEEK和15 vol.% Si3N4-PEEK)是3d打印的,包括固体和多孔笼设计。笼子按照ASTM F2077进行静态压缩、压缩剪切和扭转测试。用表皮葡萄球菌和大肠杆菌分别接种原丝和复合丝进行抑菌试验。使用MC3T3-E1小鼠成骨前细胞进行体外细胞测试,测量细胞增殖、累积矿化和成骨活性。3d打印的PEEK和Si3N4-PEEK保持架在所有设计中都表现出足够的机械强度,压缩强度超过14.7 kN,压缩剪切强度超过6.9 kN。与PEEK相比,Si3N4-PEEK的细菌粘附水平显著降低,降低了93.9% (1.21 log),并增强了细胞增殖。Si3N4-PEEK将允许定制制造3d打印脊柱植入物,与未填充的PEEK或金属合金相比,可以降低感染风险。
{"title":"Exploring the mechanical strength, antimicrobial performance, and bioactivity of 3D-printed silicon nitride-PEEK composites in cervical spinal cages.","authors":"Cemile Basgul, Paul DeSantis, Tabitha Derr, Noreen J Hickok, Ryan M Bock, Steven M Kurtz","doi":"10.36922/ijb.2124","DOIUrl":"10.36922/ijb.2124","url":null,"abstract":"<p><p>In this study, our goal was to assess the suitability of a polyether-ether-ketone (PEEK) and silicon nitride (Si<sub>3</sub>N<sub>4</sub>) polymer composite for antimicrobial three-dimensional (3D)-printed cervical cages. Generic cage designs (PEEK and 15 vol.% Si<sub>3</sub>N<sub>4</sub>-PEEK) were 3D-printed, including solid and porous cage designs. Cages were tested in static compression, compression shear, and torsion per ASTM F2077. For antibacterial testing, virgin and composite filament samples were inoculated with <i>Staphylococcus epidermidis</i> and <i>Escherichia coli</i>. <i>In vitro</i> cell testing was conducted using MC3T3-E1 mouse preosteoblasts, where cell proliferation, cumulative mineralization, and osteogenic activity were measured. The 3D-printed PEEK and Si<sub>3</sub>N<sub>4</sub>-PEEK cages exhibited adequate mechanical strength for all designs, exceeding 14.7 kN in compression and 6.9 kN in compression shear. Si<sub>3</sub>N<sub>4</sub>-PEEK exhibited significantly lower bacterial adhesion levels, with a 93.9% reduction (1.21 log), and enhanced cell proliferation when compared to PEEK. Si<sub>3</sub>N<sub>4</sub>-PEEK would allow for custom fabrication of 3D-printed spinal implants that reduce the risk of infection compared to unfilled PEEK or metallic alloys.</p>","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":"10 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced osteogenesis and bactericidal performance of additively manufactured MgO-and Cu-added CpTi for load-bearing implants 增材制造的mgo和添加cu的CpTi用于承重植入物的成骨和杀菌性能增强
3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-10-11 DOI: 10.36922/ijb.1167
Sushant Ciliveri, Amit Bandyopadhyay
The bio-inertness of titanium, which is the ultimate choice of metallic material for implant applications, causes delayed bone&ndash;tissue integration at the implant site and prevents expedited healing for the patient. This can result in a severe issue for patients with immunocompromised bone health as titanium does not offer inherent antimicrobial properties, and thus, infections at the implant site are another concern. Current strategies addressing the issues above include using cemented implants as a coating on Ti6Al4V bulk material for orthopedic applications. Roadblock arises with coating failure due to weak interfacial bond at the Ti&ndash;cement interface, which necessitates revision surgeries. In this study, we added osteogenic MgO and antibacterial Cu to commercially pure titanium (CpTi) and processed them using metal additive manufacturing. Mg, an essential trace element in the body, has been proven to enhance osseointegration in vivo. Cu has been popular for its bactericidal capabilities. With the addition of 1 wt.% of MgO to the CpTi matrix, we observed a four-fold increase in the mineralized bone formation at the bone&ndash;implant interface in vivo. The addition of 3 wt.% of Cu did not result in cytotoxicity, and adding Cu to CpTi-MgO chemical makeup yielded in vivo performance similar to that in CpTi-MgO. In in vitro bacterial studies with gram-positive Staphylococcus aureus, CpTi-MgO-Cu displayed an antibacterial efficacy of 81% at the end of 72 h of culture. Our findings highlight the synergistic benefits of CpTi-MgO-Cu, which exhibit superior early-stage osseointegration and antimicrobial capabilities.
钛的生物惰性是种植体应用的金属材料的最终选择,它会导致种植体部位的骨和组织整合延迟,并阻碍患者的快速愈合。由于钛不具有固有的抗菌特性,这可能会给骨骼免疫功能低下的患者带来严重的问题,因此,种植体部位的感染是另一个问题。目前解决上述问题的策略包括使用骨水泥植入物作为矫形应用的Ti6Al4V块状材料的涂层。由于Ti& ash;水泥界面的界面结合较弱,导致涂层失效,这就需要进行翻修手术。在本研究中,我们将成骨MgO和抗菌Cu添加到商业纯钛(CpTi)中,并使用金属增材制造对其进行加工。镁是人体必需的微量元素,已被证明能促进体内骨整合。铜因其杀菌能力而广受欢迎。在CpTi基质中加入1 wt.%的MgO后,我们观察到体内骨和种植体界面的矿化骨形成增加了4倍。添加3 wt.%的Cu不会导致细胞毒性,并且在CpTi-MgO化学组成中添加Cu产生的体内性能与CpTi-MgO相似。在革兰氏阳性金黄色葡萄球菌的体外细菌研究中,CpTi-MgO-Cu在培养72 h时的抗菌效果为81%。我们的研究结果强调了CpTi-MgO-Cu的协同效益,它表现出优越的早期骨整合和抗菌能力。
{"title":"Enhanced osteogenesis and bactericidal performance of additively manufactured MgO-and Cu-added CpTi for load-bearing implants","authors":"Sushant Ciliveri, Amit Bandyopadhyay","doi":"10.36922/ijb.1167","DOIUrl":"https://doi.org/10.36922/ijb.1167","url":null,"abstract":"The bio-inertness of titanium, which is the ultimate choice of metallic material for implant applications, causes delayed bone&amp;ndash;tissue integration at the implant site and prevents expedited healing for the patient. This can result in a severe issue for patients with immunocompromised bone health as titanium does not offer inherent antimicrobial properties, and thus, infections at the implant site are another concern. Current strategies addressing the issues above include using cemented implants as a coating on Ti6Al4V bulk material for orthopedic applications. Roadblock arises with coating failure due to weak interfacial bond at the Ti&amp;ndash;cement interface, which necessitates revision surgeries. In this study, we added osteogenic MgO and antibacterial Cu to commercially pure titanium (CpTi) and processed them using metal additive manufacturing. Mg, an essential trace element in the body, has been proven to enhance osseointegration in vivo. Cu has been popular for its bactericidal capabilities. With the addition of 1 wt.% of MgO to the CpTi matrix, we observed a four-fold increase in the mineralized bone formation at the bone&amp;ndash;implant interface in vivo. The addition of 3 wt.% of Cu did not result in cytotoxicity, and adding Cu to CpTi-MgO chemical makeup yielded in vivo performance similar to that in CpTi-MgO. In in vitro bacterial studies with gram-positive Staphylococcus aureus, CpTi-MgO-Cu displayed an antibacterial efficacy of 81% at the end of 72 h of culture. Our findings highlight the synergistic benefits of CpTi-MgO-Cu, which exhibit superior early-stage osseointegration and antimicrobial capabilities.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":"203 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136213526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Strontium-doped calcium silicate scaffolds with enhanced mechanical properties and tunable biodegradability fabricated by vat photopolymerization 用还原光聚合法制备具有增强力学性能和可调生物降解性的掺锶硅酸钙支架
3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-09-14 DOI: 10.36922/ijb.1233
Yinjin Li, Jin Su, Annan Chen, Yifei Li, Xi Yuan, Kezhuo Chen, Zhaoqing Li, Chunze Yan, Jian Lu, Yusheng Shi
&nbsp;Strontium-doped calcium silicate (SrCS) bioceramics have demonstrated outstanding vasculogenic ability to repair large segmental bone defects, while their poor mechanical properties and rapid degradation rate remain the major obstacles in clinical treatment. Here, we proposed a novel approach to significantly enhance the mechanical properties of SrCS bioceramics with tunable biodegradability using micron barium titanate-based (BTA) powders as a dopant. Biomimetic SrCS-BTA scaffolds with triply periodic minimal surface structures were fabricated by vat photopolymerization. The effects of BTA content on microtopography, mechanical properties, degradability, and bioactivity of composite scaffolds were studied. On the one hand, the BTA greatly increased the maximum densification rate of SrCS ceramics by 84.37%, while the corresponding densification temperature decreased by 95&deg;C. On the other hand, CaTiO3 generated by the reaction of SrCS and BTA intercepted cracks at the grain boundaries, and thus, the mechanical properties were enhanced due to the pinning effect. The SrCS-40BTA scaffold exhibited much higher compressive strength and elastic modulus by 296% compared with the pure SrCS scaffold. The energy absorption of SrCS-40BTA scaffolds was 5.6 times higher than that of the pure SrCS scaffold. In addition, biocompatible SrCS-BTA scaffolds with lower degradation rates can play a supporting role in the process of repair for a longer duration. This work provides a promising strategy to fabricate biomimetic scaffolds with highly enhanced mechanical properties and tunable biodegradability for repairing damaged large segmental bone tissues.
锶掺杂硅酸钙(SrCS)生物陶瓷在修复大节段骨缺损方面表现出了出色的血管生成能力,但其力学性能差、降解速度快仍然是临床治疗的主要障碍。在这里,我们提出了一种新的方法,以微米钛酸钡基(BTA)粉末作为掺杂剂,显著提高具有可调节生物降解性的SrCS生物陶瓷的力学性能。采用还原光聚合法制备了具有三周期最小表面结构的仿生SrCS-BTA支架。研究了BTA含量对复合支架微形貌、力学性能、可降解性和生物活性的影响。一方面,BTA使SrCS陶瓷的最大致密化率提高了84.37%,而致密化温度降低了95℃;另一方面,由SrCS和BTA反应生成的CaTiO3在晶界处拦截裂纹,从而由于钉钉效应而提高了力学性能。与纯SrCS相比,SrCS- 40bta支架的抗压强度和弹性模量提高了296%。SrCS- 40bta支架的吸能比纯SrCS支架高5.6倍。此外,具有较低降解率的生物相容性SrCS-BTA支架可以在更长的修复过程中发挥支持作用。这项工作为制造具有高机械性能和可调节生物降解性的仿生支架修复受损的大节段骨组织提供了一种有前途的策略。
{"title":"Strontium-doped calcium silicate scaffolds with enhanced mechanical properties and tunable biodegradability fabricated by vat photopolymerization","authors":"Yinjin Li, Jin Su, Annan Chen, Yifei Li, Xi Yuan, Kezhuo Chen, Zhaoqing Li, Chunze Yan, Jian Lu, Yusheng Shi","doi":"10.36922/ijb.1233","DOIUrl":"https://doi.org/10.36922/ijb.1233","url":null,"abstract":"&amp;nbsp;Strontium-doped calcium silicate (SrCS) bioceramics have demonstrated outstanding vasculogenic ability to repair large segmental bone defects, while their poor mechanical properties and rapid degradation rate remain the major obstacles in clinical treatment. Here, we proposed a novel approach to significantly enhance the mechanical properties of SrCS bioceramics with tunable biodegradability using micron barium titanate-based (BTA) powders as a dopant. Biomimetic SrCS-BTA scaffolds with triply periodic minimal surface structures were fabricated by vat photopolymerization. The effects of BTA content on microtopography, mechanical properties, degradability, and bioactivity of composite scaffolds were studied. On the one hand, the BTA greatly increased the maximum densification rate of SrCS ceramics by 84.37%, while the corresponding densification temperature decreased by 95&amp;deg;C. On the other hand, CaTiO3 generated by the reaction of SrCS and BTA intercepted cracks at the grain boundaries, and thus, the mechanical properties were enhanced due to the pinning effect. The SrCS-40BTA scaffold exhibited much higher compressive strength and elastic modulus by 296% compared with the pure SrCS scaffold. The energy absorption of SrCS-40BTA scaffolds was 5.6 times higher than that of the pure SrCS scaffold. In addition, biocompatible SrCS-BTA scaffolds with lower degradation rates can play a supporting role in the process of repair for a longer duration. This work provides a promising strategy to fabricate biomimetic scaffolds with highly enhanced mechanical properties and tunable biodegradability for repairing damaged large segmental bone tissues.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134972970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Uncovering advances in final end-user applications, user acceptability, quality assurance, and digital technologies for 3D-printed oral drug delivery systems 揭示3d打印口服给药系统在最终用户应用、用户可接受性、质量保证和数字技术方面的进展
3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-09-08 DOI: 10.36922/ijb.1119
Veronica L. Rios-Mata, Marisela Rodriguez-Salvador, Jia An, Chee Kai Chua, Pedro F. Castillo-Valdez
The increasing demand for innovative drugs and personalized treatment is radically changing the pharmaceutical industry, where significant efforts in research and development (R&D) are taking place. Three-dimensional (3D) printing offers interesting solutions for these demands, solving some of the limitations of current manufacturing processes. 3D-printed oral drug delivery systems can improve the delivery of pharmaceutical substances in the body, and the dynamic interaction between pharmaceutical ingredients, while providing personalized formulations, geometries, sizes, controlled release rates, and increasing time in the gastrointestinal tract. Advances in 3D printing for oral drug delivery systems have been investigated in terms of processes, materials, and effects. However, it is important to also consider other topics, such as the specific needs of the users to enhance drugs acceptability, the quality control processes due to the absence of approved guidelines, and the digitalization of the industry to respond to future challenges of the digital era; nevertheless, there are no studies that comprise these elements. To fill this gap, the aim of this research is to identify advances in terms of final end-user applications, quality assurance, user acceptability, and digital technologies for 3D-printed oral drug delivery systems. To accomplish this, a competitive technology intelligence (CTI) methodology was applied, where scientific literature was retrieved from the Web of Science covering the period from January 1, 1900, to May 1, 2023. For this task, a scientometric analysis was performed, and the main trends involving the previously mentioned elements were identified. In the first case, 3D-printed oral drug delivery systems are being designed for different purposes, including as anti-deterrent formulations to decrease the global problem of opioid abuse. For quality assurance, the results demonstrated the implementation of approaches like quality by design to increase the quality of the 3D-printed dosage forms. In the case of user acceptability, the interest in creating more attractive formulations was identified; for this, innovative technologies such as ColorJet 3D printing are being used. Lastly, regarding digital technologies, the importance of cyberattacks while sending the 3D-printed dosage form file to the 3D printer is highlighted; for this, cybersecurity systems are being studied. The outcomes of this study can add value to researchers, organizations, and investment firms interested in the R&D of novel and personalized treatments, and the areas of 3D printing, pharmaceutical, medical, and health. &nbsp; &nbsp;
对创新药物和个性化治疗日益增长的需求正在从根本上改变制药行业,该行业正在进行重大的研究和开发(R&D)。三维(3D)打印为这些需求提供了有趣的解决方案,解决了当前制造工艺的一些限制。3d打印的口服给药系统可以改善药物在体内的传递,以及药物成分之间的动态相互作用,同时提供个性化的配方、几何形状、大小、可控释放率,并增加在胃肠道中的时间。3D打印用于口服药物输送系统的进展已经在工艺、材料和效果方面进行了研究。然而,也必须考虑其他主题,例如用户提高药物可接受性的特定需求,由于缺乏批准指南而导致的质量控制过程,以及行业的数字化以应对数字时代的未来挑战;然而,没有研究包含这些要素。为了填补这一空白,本研究的目的是确定3d打印口服给药系统在最终用户应用、质量保证、用户可接受性和数字技术方面的进展。为了实现这一目标,我们采用了竞争技术情报(CTI)方法,从科学网上检索了从1900年1月1日到2023年5月1日的科学文献。为了完成这项任务,我们进行了科学计量分析,并确定了涉及上述元素的主要趋势。在第一个案例中,3d打印的口服药物输送系统被设计用于不同的目的,包括作为反威慑配方,以减少阿片类药物滥用的全球问题。为了保证质量,结果证明了通过设计提高质量等方法的实施,以提高3d打印剂型的质量。在用户可接受的情况下,确定了创造更有吸引力的配方的兴趣;为此,正在使用ColorJet 3D打印等创新技术。最后,关于数字技术,在将3D打印的剂型文件发送到3D打印机时,强调了网络攻击的重要性;为此,人们正在研究网络安全系统。这项研究的结果可以为研究人员、组织和投资公司增加价值,这些公司对新型和个性化治疗的研发以及3D打印、制药、医疗和健康领域感兴趣。,,,,
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引用次数: 0
Bioprinting of cell-laden protein-based hydrogels: From cartilage to bone tissue engineering 细胞载蛋白水凝胶的生物打印:从软骨到骨组织工程
3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-09-07 DOI: 10.36922/ijb.1089
Mehran Khajehmohammadi, Negar Bakhtiary, Niyousha Davari, Soulmaz Sarkari, Hamidreza Tolabi, Dejian Li, Behafarid Ghalandari, Baoqing Yu, Farnaz Ghorbani
The fabrication of cell-laden protein-based hydrogels (PBHs) for bioprinting necessitates careful consideration of numerous factors to ensure optimal structure and functionality. Bioprinting techniques, such as single-cell, multi-cell, and cell aggregate bioprinting, are employed to encapsulate cells within PBHs bioink, enabling the creation of scaffolds for cartilage and bone regeneration. During the fabrication process, it is imperative to account for biophysical and biochemical factors that influence cell behavior and protein structure within the PBHs. Precise control of crosslinking methods, hydrogel rheological properties, and printing parameters is also crucial to achieve desired scaffold properties without compromising cell viability and protein integrity. This review primarily focuses on the influence of biophysical factors, including composition, microstructure, biodegradation, and crosslinking, as well as biochemical factors, including chemical structure, growth factors, and signaling molecules, on protein structure and cell behavior. Additionally, key considerations for bioprinting PBHs and their impact on the successful regeneration of tissues are discussed. Furthermore, the review highlights current advancements, existing challenges, and promising prospects in the development of cell-laden PBHs for bioprinting applications and the regeneration of bone and cartilage.
用于生物打印的细胞负载蛋白基水凝胶(PBHs)的制造需要仔细考虑许多因素,以确保最佳的结构和功能。生物打印技术,如单细胞、多细胞和细胞聚合生物打印,被用于将细胞包裹在PBHs生物链接中,从而能够创建软骨和骨再生的支架。在制造过程中,必须考虑影响pbh内细胞行为和蛋白质结构的生物物理和生化因素。精确控制交联方法、水凝胶流变特性和打印参数对于在不影响细胞活力和蛋白质完整性的情况下实现所需的支架特性也至关重要。本文主要综述了生物物理因素(包括组成、微观结构、生物降解和交联)和生化因素(包括化学结构、生长因子和信号分子)对蛋白质结构和细胞行为的影响。此外,还讨论了生物打印pbh的关键考虑因素及其对组织成功再生的影响。此外,本文还重点介绍了负载细胞pbh在生物打印和骨软骨再生方面的发展现状、存在的挑战和前景。
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引用次数: 0
Evaluation of a synthetic peptide-based bioink (PeptiInk Alpha 1) for in vitro 3D bioprinting of cartilage tissue models 合成肽基生物链接(PeptiInk Alpha 1)用于软骨组织模型体外3D生物打印的评价
3区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-09-06 DOI: 10.36922/ijb.0899
Patricia Santos-Beato, Andrew A. Pitsillides, Alberto Saiani, Aline Miller, Ryo Torii, Deepak M. Kalaskar
Cartilage pathology in human disease is poorly understood and requires further research. Various attempts have been made to study cartilage pathologies using in vitro human cartilage models as an alternative for preclinical research. Three-dimensional (3D) bioprinting is a technique that has been used to 3D-bioprint cartilage tissue models in vitro using animal-derived materials such as gelatine or hyaluronan, which present challenges in terms of scalability, reproducibility, and ethical concerns. We present an assessment of synthetic self-assembling peptides as bioinks for bioprinted human in vitro cartilage models. Primary human chondrocytes were mixed with PeptiInk Alpha 1, 3D-bioprinted and cultured for 14 days, and compared with 3D chondrocyte pellet controls. Cell viability was assessed through LIVE/DEAD assays and DNA quantification. High cell viability was observed in the PeptiInk culture, while a fast decrease in DNA levels was observed in the 3D pellet control. Histological evaluation using hematoxylin and eosin staining and immunofluorescence labeling for SOX-9, collagen type II, and aggrecan showed a homogeneous cell distribution in the 3D-bioprinted PeptiInks as well as high expression of chondrogenic markers in both control and PeptiInk cultures. mRNA expression levels assessed by - qRT-PCR (quantitative real time-polymerase chain reaction) confirmed chondrogenic cell behavior. These data showed promise in the potential use of PeptiInk Alpha 1 as a bioprintable manufacturing material for human cartilage in vitro models.
软骨病理在人类疾病的了解很少,需要进一步的研究。利用体外人软骨模型作为临床前研究的替代方法,已经进行了各种各样的尝试来研究软骨病理。三维(3D)生物打印是一种使用动物源性材料(如明胶或透明质酸)体外3D生物打印软骨组织模型的技术,但在可扩展性、可重复性和伦理问题方面存在挑战。我们提出了一种评估合成自组装肽作为生物打印人类体外软骨模型的生物墨水。将人原代软骨细胞与PeptiInk Alpha 1混合,3D打印培养14天,并与3D软骨细胞颗粒对照进行比较。通过LIVE/DEAD测定和DNA定量评估细胞活力。在PeptiInk培养中观察到高细胞活力,而在3D颗粒对照中观察到DNA水平快速下降。使用苏木精和伊红染色以及免疫荧光标记对SOX-9、II型胶原和聚集蛋白进行组织学评估显示,3d生物打印的PeptiInk中细胞分布均匀,并且在对照和PeptiInk培养物中软骨标志物的高表达。通过定量实时聚合酶链反应(qRT-PCR)评估mRNA表达水平证实了软骨细胞的行为。这些数据显示了PeptiInk Alpha 1作为人体软骨体外模型的生物可打印制造材料的潜力。
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International Journal of Bioprinting
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