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Pharmaceutical excipients: Metamorphosis from conventional formulation to 3D printing 药用辅料:从传统配方到3D打印的蜕变
Q1 Computer Science Pub Date : 2025-11-12 DOI: 10.1016/j.bprint.2025.e00454
Amit Kumar Das , Akramul Ansary , Bhargab Jyoti Sahariah , Nilutpal Sharma Bora
Pharmaceutical excipients have undergone a paradigm shift from traditionally inert formulation components to advanced functional materials that play critical roles in drug delivery, stability, manufacturability, and therapeutic efficacy. This review explores the transformation of excipients in the context of modern pharmaceutical manufacturing, with particular emphasis on their integration into additive manufacturing technologies such as 3D printing. Novel excipients—including smart polymers, co-processed materials, bioinspired nanostructures, and environmentally sustainable agents—have demonstrated enhanced rheological, thermal, and structural properties necessary for layer-by-layer drug fabrication. These advancements support the development of complex dosage forms, personalized medicines, and controlled-release systems that cannot be achieved through conventional manufacturing. Additionally, regulatory and analytical challenges associated with novel excipients are discussed, highlighting the need for global harmonization and advanced validation methods. As pharmaceutical manufacturing continues to embrace digital and precision-driven technologies, the strategic design and application of next-generation excipients will be central to enabling scalable, safe, and patient-centric drug delivery systems.
药用辅料经历了从传统惰性配方成分到先进功能材料的范式转变,这些功能材料在给药、稳定性、可制造性和治疗效果方面发挥着关键作用。这篇综述探讨了赋形剂在现代制药制造背景下的转变,特别强调了它们与增材制造技术(如3D打印)的整合。新型赋形剂——包括智能聚合物、协同加工材料、生物启发纳米结构和环境可持续剂——已经证明了对逐层药物制造所必需的增强的流变学、热学和结构特性。这些进步支持了复杂剂型、个体化药物和控释系统的开发,这些都是传统制造无法实现的。此外,还讨论了与新型辅料相关的监管和分析挑战,强调了全球统一和先进验证方法的必要性。随着制药制造不断采用数字化和精确驱动技术,下一代赋形剂的战略设计和应用将成为实现可扩展、安全和以患者为中心的给药系统的核心。
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引用次数: 0
Engineering in vitro vascularization: Enhanced network formation in bioprinted, vat photopolymerized dECM constructs 体外血管化工程:在生物打印、还原光聚合的dECM结构中增强网络形成
Q1 Computer Science Pub Date : 2025-11-11 DOI: 10.1016/j.bprint.2025.e00452
Kristin Schüler , Ahed Almalla , Sebastian Seitel , Friederike Ebner , Sebastian Seiffert , Marie Weinhart , Laura Elomaa
Formation of blood vessels sustaining the metabolic demands of the tissue-forming cells remains the greatest challenge in engineered tissues for regenerative medicine and in vitro organ modelling. We investigated vascularization of covalently crosslinked hydrogels derived from porcine decellularized small intestinal submucosa (dSIS), focusing on optimizing conditions for bioprinting and subsequent vascular network formation. dSIS was solubilized via enzymatic digestion with papain and formulated into a photocrosslinkable bioresin by combining it with a photoinitiator system of ruthenium/sodium persulfate (Ru/SPS) and human umbilical vein endothelial cells (HUVECs). This bioresin allowed bioprinting of cell-laden dSIS hydrogels via vat photopolymerization. Cytotoxicity testing of the bioresins revealed high viability of HUVECs encapsulated in the dSIS hydrogels, and coculturing the bioprinted HUVEC-laden hydrogels in presence of human dermal fibroblasts resulted in the formation of an interconnected vascular network within the gels. A lower Ru/SPS concentration (0.25/5 mM) in the bioresin led to the formation of a denser vascular network compared to the higher one (0.5/5 mM), indicating the significance of the Ru/SPS concentration in the covalent hydrogel crosslinking and the subsequent vascularization. The lowest dSIS concentration (0.375 wt-%) yielded soft hydrogels with incomplete printing fidelity, while the stiffest (0.75 wt-%) hydrogels failed to support the HUVEC network formation. The dSIS concentration of 0.5 wt-% was found optimal for both the bioprinting fidelity and the vascular network formation. Our findings highlighted the need for optimizing hydrogel composition and thus its covalent crosslinking for efficient vascularization of bioprinted tissue constructs, with potential implications for further development of vascularized 3D tissue models.
血管的形成维持组织形成细胞的代谢需求仍然是再生医学和体外器官建模工程组织的最大挑战。我们研究了猪脱细胞小肠粘膜下层(dSIS)的共价交联水凝胶的血管化,重点研究了生物打印和随后血管网络形成的优化条件。dSIS经木瓜蛋白酶酶解溶解,并与钌/过硫酸钠(Ru/SPS)和人脐静脉内皮细胞(HUVECs)的光引发剂体系结合制成光交联生物树脂。这种生物树脂允许生物打印细胞负载的dSIS水凝胶通过还原光聚合。生物树脂的细胞毒性测试显示,包裹在dSIS水凝胶中的HUVECs具有很高的活力,并且将生物打印的HUVECs水凝胶与人类真皮成纤维细胞共培养,导致凝胶内形成相互连接的血管网络。生物树脂中较低的Ru/SPS浓度(0.25/5 mM)比较高的Ru/SPS浓度(0.5/5 mM)形成了更致密的血管网络,这表明Ru/SPS浓度在共价水凝胶交联和随后的血管化过程中具有重要意义。最低dSIS浓度(0.375 wt-%)产生的软水凝胶具有不完整的打印保真度,而最硬的水凝胶(0.75 wt-%)无法支持HUVEC网络的形成。发现dSIS浓度为0.5 wt-%对生物打印保真度和血管网络形成都是最佳的。我们的研究结果强调了优化水凝胶组成及其共价交联的必要性,以实现生物打印组织结构的高效血管化,这对血管化3D组织模型的进一步发展具有潜在的意义。
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引用次数: 0
Bioprinting microbial harmony: Engineering spatially organized probiotic ecosystems via chaotic bioprinting 生物打印微生物和谐:通过混沌生物打印工程空间组织的益生菌生态系统
Q1 Computer Science Pub Date : 2025-11-11 DOI: 10.1016/j.bprint.2025.e00453
Francisco Javier Flores-Loera , Ariel Cantoral-Sánchez , Luis Fernando Carmona-Ramirez , Ilsa Pamela de los Santos-Hernández , Saulo Montaño-Medina , David Cantú-Fernández , Esther Pérez-Carrillo , José Rodríguez-Rodríguez , Claudia Maribel Luna-Aguirre , Francisco Javier Sierra-Valdez , Grissel Trujillo-de Santiago , Mario Moisés Alvarez
Probiotic therapies offer great potential for addressing gut dysbiosis, but current approaches are limited by low strain diversity, high production costs, and the challenges of culturing strict anaerobes. To overcome these limitations, this work introduces a novel strategy based on continuous chaotic bioprinting to create structured cocultures of probiotic bacteria. Using a Kenics static mixer–based printhead, we fabricated alginate hydrogel filaments with an internal multilayered microarchitecture containing four probiotic strains: Bifidobacterium bifidum, Bacteroides fragilis, Lactobacillus rhamnosus, and Streptococcus thermophilus.
The spatial arrangement of the multilayered architecture was designed to promote cooperative interactions, particularly by embedding strict anaerobes between facultative anaerobes to create self-sustaining hypoxic niches. The printed constructs were characterized over 72 h using fluorescence microscopy, colony-forming unit counts, LIVE/DEAD assays, qPCR, gas chromatography, and dynamic mechanic analysis. Results showed that structured cocultures exhibited higher viability, enhanced growth, and more balanced population dynamics than the monocultures of each bacterial strain and unstructured (scrambled) cocultures. Short-Chain Fatty Acid Production suggests functional cross-feeding; coculture filaments exhibited notably higher levels of acetic and propionic acids than the corresponding monocultures.
This study demonstrates that chaotic bioprinting enables precise spatial control over microbial ecosystems, allowing the rational design of microbial communities with tailored interactions.
Furthermore, chaotically printed constructs preserved probiotic viability for at least six weeks under storage, survived food-buffered gastric simulations, and maintained structural integrity over time, underscoring their robustness and translational potential. Chaotic bacterial bioprinting presents a powerful and scalable platform for next-generation probiotic production and opens new opportunities for engineered microbiomes, synthetic biology, and living material design.
益生菌疗法为解决肠道生态失调提供了巨大的潜力,但目前的方法受到菌株多样性低、生产成本高和培养严格厌氧菌的挑战的限制。为了克服这些限制,本工作引入了一种基于连续混沌生物打印的新策略,以创建益生菌的结构化共培养。利用Kenics静态混合器打印头,我们制备了海藻酸盐水凝胶细丝,其内部具有多层微结构,含有四种益生菌菌株:两歧双歧杆菌、脆弱拟杆菌、鼠李糖乳杆菌和嗜热链球菌。多层建筑的空间安排旨在促进合作互动,特别是通过在兼性厌氧菌之间嵌入严格的厌氧菌,以创造自我维持的缺氧生态位。通过荧光显微镜、菌落形成单位计数、LIVE/DEAD测定、qPCR、气相色谱和动态力学分析对打印的构建体进行了72h的表征。结果表明,与单一培养和非结构化共培养相比,结构化共培养具有更高的生存能力、更强的生长能力和更平衡的种群动态。短链脂肪酸的产生提示功能性交叉饲养;共培养花丝的乙酸和丙酸含量明显高于单株。该研究表明,混沌生物打印可以对微生物生态系统进行精确的空间控制,从而可以通过定制的相互作用来合理设计微生物群落。此外,无序打印的构建物在储存中至少能保持益生菌活力六周,在食物缓冲的胃模拟中存活下来,并随着时间的推移保持结构完整性,强调了它们的稳健性和转化潜力。混沌细菌生物打印为下一代益生菌生产提供了一个强大的、可扩展的平台,并为工程微生物组、合成生物学和生物材料设计开辟了新的机会。
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引用次数: 0
Real-time force and rheological measurement for hydrogels 3D bioprinting using a piston-driven extrusion system 使用活塞驱动挤出系统进行水凝胶3D生物打印的实时力和流变性测量
Q1 Computer Science Pub Date : 2025-10-30 DOI: 10.1016/j.bprint.2025.e00446
Jéssica Heline Lopes da Fonseca , Ingri Julieth Mancilla Corzo , Rafael Abboud Azoubel , Rêner Pontes Tavares , Violeta Carvalho , Senhorinha F.C.F. Teixeira , José Luis Dávila , Marcos Akira d'Ávila
This study introduces and validates a custom load cell integrated into a 3D printer head for the in-situ measurement of pressures and rheological behavior during hydrogel printing in a piston-driven extrusion printer. In-situ force measurements were performed during extrusion of the three hydrogel formulations with distinct rheological properties to validate the load cell approach. The extrusion forces were converted into pressure values, and compared with predictions from analytical models, and further validated using Computational Fluid Dynamics (CFD) simulations, demonstrating a strong agreement. Apparent shear stress and viscosities were estimated from the extrusion force data using capillary rheometry principles and closely matched steady-shear values obtained from conventional rheometry. The load cell system was also used to investigate the effects of printing speed and needle diameter on extrusion behavior and print fidelity using CMC/CNC hydrogels. Higher printing speeds and narrower needle diameters resulted in increased extrusion pressures, significantly impacting shape fidelity. These findings are particularly relevant for 3D bioprinting, where real-time control of material properties is needed to balance resolution and cell viability.
本研究介绍并验证了集成在3D打印机头中的定制称重传感器,用于在活塞驱动的挤出打印机中水凝胶打印过程中的压力和流变行为的原位测量。在挤压具有不同流变特性的三种水凝胶配方期间进行了现场力测量,以验证称重传感器方法。将挤压力转换为压力值,并与分析模型的预测结果进行比较,并通过计算流体动力学(CFD)模拟进一步验证,结果表明两者非常吻合。表观剪切应力和黏度是利用毛细管流变学原理从挤压力数据中估计出来的,并与常规流变学得到的稳定剪切值密切匹配。该称重传感器系统还用于研究打印速度和针径对CMC/CNC水凝胶挤出行为和打印保真度的影响。更高的印刷速度和更窄的针径导致挤压压力增加,显著影响形状保真度。这些发现与3D生物打印特别相关,需要实时控制材料特性以平衡分辨率和细胞活力。
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引用次数: 0
Development of iPSC-derived full-thickness human skin via droplet-based 3D bioprinting 利用液滴生物3D打印技术制备ipsc衍生的全层人体皮肤
Q1 Computer Science Pub Date : 2025-10-28 DOI: 10.1016/j.bprint.2025.e00445
Jieun Baek , Yudong Hong , Donghyun Lee , Ashley Hyomin Roh , C-Yoon Kim , Hyung Min Chung , Ji-Heon Lee , KyoungWhee Jeon
This study successfully established a full-thickness artificial skin model (CLE-iFTs) composed solely of human iPSC-derived fibroblasts (FBs) and keratinocytes (KCs) using a 3D bioprinting system. To evaluate the validity and performance of this model, we compared it with a manually fabricated counterpart (M-iPSC-FTs).
Quantitative analysis revealed that the keratinocyte proliferation rate in CLE-iFTs, as indicated by the percentage of Ki-67 positive cells (18.7 ± 1.2 %, p < 0.01), was significantly higher than in M-iPSC-FTs (9.7 ± 2.8 %). The basal epidermal marker KRT14 showed an average integrated density of 79,621.67 ± 3913.36 in CLE-iFTs and 75,442 ± 3913.36 in M-iPSC-FTs (p < 0.05), while the suprabasal marker KRT10 exhibited an integrated density of 247,260.33 ± 15,570.34 and 193,760 ± 24,214.66, respectively (p < 0.01), indicating stronger epidermal differentiation in the bioprinted model.
In addition, the dermis of CLE-iFTs demonstrated faster cell proliferation and higher cellular density compared to the manual model. Functional assessments further revealed that CLE-iFTs exhibited greater resistance to chemically induced cytotoxicity (IC50 value: 3.087 mg/mL vs. 2.761 mg/mL, p < 0.05) and a more favorable response to UVB irradiation, as evidenced by lower MMP-1 expression (p < 0.001) and higher Pro-collagen levels (p < 0.01).
In conclusion, the CLE-iFTs model provides superior reproducibility, enhanced structural integrity, and improved functional performance compared to manually fabricated models. These results highlight the potential of CLE-iFTs as a robust and reliable platform for advanced skin research, disease modeling, and regenerative medicine applications.
本研究利用生物3D打印系统成功建立了完全由人ipsc衍生成纤维细胞(FBs)和角质形成细胞(KCs)组成的全层人造皮肤模型(CLE-iFTs)。为了评估该模型的有效性和性能,我们将其与手工制作的对应模型(M-iPSC-FTs)进行了比较。定量分析显示,CLE-iFTs的角质细胞增殖率(Ki-67阳性细胞比例为18.7±1.2%,p < 0.01)显著高于M-iPSC-FTs(9.7±2.8%)。基底表皮标记KRT14在CLE-iFTs和M-iPSC-FTs中的平均整合密度分别为79,621.67±3913.36 (p < 0.05)和75,442±3913.36 (p < 0.05),而基底上标记KRT10的平均整合密度分别为247,260.33±15,570.34和193,760±24,214.66 (p < 0.01),表明生物打印模型中表皮分化更强。此外,与手工模型相比,CLE-iFTs的真皮细胞增殖更快,细胞密度更高。功能评估进一步显示,CLE-iFTs对化学诱导的细胞毒性具有更强的抵抗力(IC50值:3.087 mg/mL vs. 2.761 mg/mL, p < 0.05),并且对UVB照射有更有利的反应,证明了较低的MMP-1表达(p < 0.001)和较高的前胶原水平(p < 0.01)。总之,与手工制作的模型相比,CLE-iFTs模型具有更好的可重复性,增强的结构完整性和改进的功能性能。这些结果突出了cle - ift作为先进皮肤研究、疾病建模和再生医学应用的强大可靠平台的潜力。
{"title":"Development of iPSC-derived full-thickness human skin via droplet-based 3D bioprinting","authors":"Jieun Baek ,&nbsp;Yudong Hong ,&nbsp;Donghyun Lee ,&nbsp;Ashley Hyomin Roh ,&nbsp;C-Yoon Kim ,&nbsp;Hyung Min Chung ,&nbsp;Ji-Heon Lee ,&nbsp;KyoungWhee Jeon","doi":"10.1016/j.bprint.2025.e00445","DOIUrl":"10.1016/j.bprint.2025.e00445","url":null,"abstract":"<div><div>This study successfully established a full-thickness artificial skin model (CLE-iFTs) composed solely of human iPSC-derived fibroblasts (FBs) and keratinocytes (KCs) using a 3D bioprinting system. To evaluate the validity and performance of this model, we compared it with a manually fabricated counterpart (M-iPSC-FTs).</div><div>Quantitative analysis revealed that the keratinocyte proliferation rate in CLE-iFTs, as indicated by the percentage of Ki-67 positive cells (18.7 ± 1.2 %, p &lt; 0.01), was significantly higher than in M-iPSC-FTs (9.7 ± 2.8 %). The basal epidermal marker KRT14 showed an average integrated density of 79,621.67 ± 3913.36 in CLE-iFTs and 75,442 ± 3913.36 in M-iPSC-FTs (p &lt; 0.05), while the suprabasal marker KRT10 exhibited an integrated density of 247,260.33 ± 15,570.34 and 193,760 ± 24,214.66, respectively (p &lt; 0.01), indicating stronger epidermal differentiation in the bioprinted model.</div><div>In addition, the dermis of CLE-iFTs demonstrated faster cell proliferation and higher cellular density compared to the manual model. Functional assessments further revealed that CLE-iFTs exhibited greater resistance to chemically induced cytotoxicity (IC<sub>50</sub> value: 3.087 mg/mL vs. 2.761 mg/mL, p &lt; 0.05) and a more favorable response to UVB irradiation, as evidenced by lower MMP-1 expression (p &lt; 0.001) and higher Pro-collagen levels (p &lt; 0.01).</div><div>In conclusion, the CLE-iFTs model provides superior reproducibility, enhanced structural integrity, and improved functional performance compared to manually fabricated models. These results highlight the potential of CLE-iFTs as a robust and reliable platform for advanced skin research, disease modeling, and regenerative medicine applications.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"52 ","pages":"Article e00445"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Polymer Degradation on Cellular Behavior in Tissue Engineering. 组织工程中聚合物降解对细胞行为的影响。
Q1 Computer Science Pub Date : 2025-10-01 Epub Date: 2025-07-30 DOI: 10.1016/j.bprint.2025.e00429
Kentaro Umemori, Dianne Little

Tissue engineering frequently employs biomimetic scaffolds to direct cell responses and facilitate the differentiation of cells into specific lineages. Biodegradable scaffolds mitigate immune responses, stress shielding concerns in load bearing tissues, and the need for secondary or revision surgical procedures for retrieval. However, during the degradation process, scaffold properties such as fiber diameter, fiber porosity, fiber alignment, surface properties and mechanical properties undergo changes that significantly alter the initial properties. This review aims to comprehensively assess the impact of degradation on scaffold properties from the perspective of their effects on cellular behavior by addressing four key aspects of polymer degradation: First, we review the variables that influence scaffold degradation. Second, we examine how degradation impacts scaffold properties. Third, we explore the effects of scaffold degradation products. Finally, we investigate measures to increase tunability of degradation rate. Harnessing and incorporating these degradation mechanisms into scaffold design holds great promise for advancing the development of tissue-engineered scaffolds, ultimately improving their efficacy and clinical utility.

组织工程经常使用仿生支架来指导细胞反应并促进细胞分化成特定的谱系。可生物降解的支架减轻了免疫反应,减轻了承载组织中的应力屏蔽问题,并减少了对二次或翻修外科手术的需要。然而,在降解过程中,支架性能如纤维直径、纤维孔隙度、纤维排列、表面性能和机械性能发生变化,显著改变了其初始性能。本综述旨在通过解决聚合物降解的四个关键方面,从降解对细胞行为的影响的角度全面评估降解对支架性能的影响:首先,我们回顾了影响支架降解的变量。其次,我们研究了降解如何影响支架性能。第三,我们探讨了支架降解产物的影响。最后,我们探讨了提高降解率可调性的措施。利用并将这些降解机制整合到支架设计中,对于推进组织工程支架的发展,最终提高其疗效和临床应用前景广阔。
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引用次数: 0
3D bioprinting of self-strengthening living materials using cellulose nanofiber-producing bacteria in sodium alginate hydrogel 利用海藻酸钠水凝胶中产生纤维素纳米纤维的细菌进行自我强化生物材料的3D生物打印
Q1 Computer Science Pub Date : 2025-09-26 DOI: 10.1016/j.bprint.2025.e00443
Nan Zhang , Imtiaz Qavi , Marco Araneda , Shaida Sultana Rumi , Noureddine Abidi , Sampa Halder , George Z. Tan
Three-dimensional (3D) bioprinting has emerged as a powerful tool for fabricating engineered living materials (ELMs). Despite recent advances in controlling the spatial distribution of bacteria in hydrogel, printing bacteria-laden hydrogels into bulk 3D structures remains a significant challenge. This study presents a partial crosslinking bioprinting strategy for fabricating bacterial cellulose (BC)-based living scaffolds using sodium alginate (SA) hydrogels embedded with Komagataeibacter xylinus. Pre-crosslinked SA was first printed to define the scaffold outline, followed by infilling with uncrosslinked, bacteria-laden SA bioink to enable in situ BC nanofiber production. As BC nanofibers formed within the hydrogel, the scaffolds exhibited self-strengthening and self-hardening property. The effects of SA concentration and culture duration on cellulose yield, rheological properties, printability, and mechanical performance were systematically evaluated. Based on the quantitative relationship between hydrogel formulation, bacterial activity, and scaffold functionality, we optimized the bioinks to enable both high-resolution printing and efficient cellulose formation. This microbial bioprinting technique provides a robust platform for constructing functional BC-based ELMs with potential applications in biomedicine and tissue engineering.
三维(3D)生物打印已经成为制造工程生物材料(elm)的有力工具。尽管最近在控制水凝胶中细菌的空间分布方面取得了进展,但将细菌负载的水凝胶打印成大块3D结构仍然是一个重大挑战。本研究提出了一种局部交联生物打印策略,利用海藻酸钠(SA)水凝胶包埋木状Komagataeibacter xylinus,制备细菌纤维素(BC)基活支架。首先打印预交联SA以确定支架轮廓,然后填充未交联的细菌SA生物链接,以实现原位BC纳米纤维的生产。由于BC纳米纤维在水凝胶中形成,支架具有自增强和自硬化的特性。系统评价了SA浓度和培养时间对纤维素产率、流变性能、印刷适性和机械性能的影响。基于水凝胶配方、细菌活性和支架功能之间的定量关系,我们优化了生物墨水,以实现高分辨率打印和高效纤维素形成。这种微生物生物打印技术为构建基于bc的功能性elm提供了一个强大的平台,在生物医学和组织工程方面具有潜在的应用前景。
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引用次数: 0
In vitro evaluation of 3D-printed PCL/forsterite scaffolds with aligned collagen and demineralized bone matrix for cranial bone regeneration 胶原-脱矿骨基质3d打印PCL/forsterite支架用于颅骨再生的体外评价
Q1 Computer Science Pub Date : 2025-09-24 DOI: 10.1016/j.bprint.2025.e00442
Fatemeh Saberi, Shohreh Mashayekhan
Developing an appropriate scaffold for cranioplasty applications remains challenging due to the high mechanical strength, controlled degradation, and support for cell migration and proliferation. Despite their common use, traditional materials such as titanium implants, bone allografts, hydroxyapatite, and poly methyl methacrylate have limitations that hinder their effectiveness. Achieving both robust mechanical performance and favorable biological properties in a single scaffold remains a significant challenge. In this study, we introduce a novel fabrication approach that combines 3D printing and directional freeze-casting to create a hybrid scaffold with enhanced structural and biological properties. A composite of polycaprolactone (PCL) and forsterite (FO) was 3D-printed to provide mechanical stability. Meanwhile, collagen and demineralized bone matrix (DBM) were freeze-cast into the pores to form radially aligned microchannels. This design enhances the biological properties and promotes cell migration by mimicking the native extracellular matrix architecture. Our results showed that adding 10 % forsterite to PCL increased the Young's modulus to 100 MPa, with 12 % degradation after one month of immersion in phosphate-buffered saline (PBS). The radially oriented collagen-DBM network supported a 2.4-fold increase in cell proliferation. Furthermore, the in vitro cell migration assay demonstrated enhanced cellular infiltration in aligned versus randomly structured scaffolds. Integrating a directional microstructure, chemical cues from ion release and DBM particles, along with a mechanically robust platform, offers a promising strategy for bone regeneration and cranioplasty applications.
由于高机械强度、可控降解和支持细胞迁移和增殖,开发适合颅骨成形术应用的支架仍然具有挑战性。尽管钛植入物、同种异体骨移植物、羟基磷灰石和聚甲基丙烯酸甲酯等传统材料被广泛使用,但它们的局限性阻碍了它们的有效性。在单一支架中实现强大的机械性能和良好的生物特性仍然是一个重大挑战。在这项研究中,我们介绍了一种新的制造方法,将3D打印和定向冷冻铸造相结合,以创建具有增强结构和生物特性的混合支架。聚己内酯(PCL)和forsterite (FO)的复合材料被3d打印以提供机械稳定性。同时,将胶原蛋白和脱矿骨基质(DBM)冻铸入孔内,形成径向排列的微通道。这种设计通过模仿天然的细胞外基质结构来增强生物特性和促进细胞迁移。我们的研究结果表明,在PCL中加入10%的forsterite可以将杨氏模量提高到100mpa,在磷酸盐缓冲盐水(PBS)中浸泡一个月后,杨氏模量降低了12%。径向导向的胶原- dbm网络支持细胞增殖增加2.4倍。此外,体外细胞迁移实验表明,排列支架与随机支架相比,细胞浸润增强。结合定向微观结构、离子释放的化学线索和DBM颗粒,以及机械坚固的平台,为骨再生和颅骨成形术应用提供了一种有前途的策略。
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引用次数: 0
Towards intelligent cultivated/cultured meat factories: The synergy of AI, 3D bioprinting and automation in next-gen food manufacturing 迈向智能养殖/养殖肉类工厂:人工智能、3D生物打印和自动化在下一代食品制造中的协同作用
Q1 Computer Science Pub Date : 2025-09-17 DOI: 10.1016/j.bprint.2025.e00441
Saumya Saraswat, Twinkle Bhargava, Juhi Landge, Kamalnayan Tibrewal
Global population growth, urbanization, and growing incomes have increased the need for protein, stressing the urgent need for sustainable alternatives to conventional livestock farming, which presents serious ethical, scalability, and environmental issues. Cultured meat, made by culturing animal cells under a controlled environment, is a possible alternative that can lower greenhouse gas emissions, land use, and animal suffering. However, large-scale production of cultured meat with the same texture, structure, and viability as conventional meat remains highly challenging. Even though three-dimensional (3D) bioprinting has become a crucial technique for precisely engineering meat-like, organized tissues, existing systems have hurdles with automation, repeatability, and throughput. The potential of recent (2020–2025) advancements in automation, Machine Learning (ML), and Artificial Intelligence (AI), primarily from the fields of regenerative medicine and tissue engineering, is examined in this paper along with its relevancy to large-scale cultured meat bioprinting.AI-driven process optimization, predictive modelling of cell viability and growth, real-time feedback through sensor-based control systems, robotic integration for material handling and post-processing, automated bioreactor integration, and early company adoption of AI and automation are some of the main topics. Research highlights advantages including less trial-and-error, improved accuracy with robotic systems, computer vision-based real-time print adjustments, and closed-loop feedback that requires less human engagement. The groundwork for intelligent, high-throughput "smart bioprinting factories" is laid by these technologies. This analysis maps out a route toward scalable, affordable cultured meat production with significant promise for industrial use and sustainable protein supply by combining advancements in AI, ML, and robotics.
全球人口增长、城市化和收入增长增加了对蛋白质的需求,迫切需要可持续的替代传统畜牧业,这带来了严重的伦理、可扩展性和环境问题。通过在受控环境下培养动物细胞制成的人造肉是一种可能的替代品,可以减少温室气体排放、土地使用和动物痛苦。然而,大规模生产具有与传统肉类相同质地,结构和活力的培养肉仍然具有很高的挑战性。尽管三维(3D)生物打印已经成为一项关键技术,用于精确地制造类肉组织,但现有的系统在自动化、可重复性和吞吐量方面存在障碍。本文研究了主要来自再生医学和组织工程领域的自动化、机器学习(ML)和人工智能(AI)最近(2020-2025)进步的潜力,以及它与大规模培养肉生物打印的相关性。人工智能驱动的过程优化、细胞活力和生长的预测建模、基于传感器的控制系统的实时反馈、材料处理和后处理的机器人集成、自动化生物反应器集成以及公司早期采用人工智能和自动化是一些主要主题。研究强调了其优点,包括减少试错,提高机器人系统的精度,基于计算机视觉的实时打印调整,以及需要更少人工参与的闭环反馈。这些技术为智能化、高通量的“智能生物打印工厂”奠定了基础。该分析通过结合人工智能、机器学习和机器人技术的进步,为可扩展的、负担得起的培养肉生产指明了一条道路,该生产在工业用途和可持续蛋白质供应方面具有重大前景。
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引用次数: 0
Oxidized alginate-gelatin nanocomposite hydrogels incorporating MXene nanosheets for 3D bioprinting 氧化海藻酸盐-明胶纳米复合水凝胶结合MXene纳米片用于3D生物打印
Q1 Computer Science Pub Date : 2025-09-17 DOI: 10.1016/j.bprint.2025.e00440
Lisa Schöbel , Mariya Tulchynska , Elmira Mohajeri , Christian Polley , Hermann Seitz , Jesus Gonzalez-Julian , Aldo R. Boccaccini
Electrically conductive hydrogels (ECHs) and electrical stimulation effectively regulate osteoblast attachment, proliferation, and differentiation, thus triggering bone tissue regeneration. Here, an alginate dialdehyde-gelatin (ADA-GEL) based hydrogel is modified with an electrically conductive and osteogenic 2D nanomaterial, namely MXene, to produce degradable and 3D printable nanocomposite hydrogels exhibiting electrical conductivity. The effect of MXene filler content on resulting hydrogel characteristics such as morphology, mechanical and electrical properties, swelling and degradation behavior was investigated comprehensively. The results indicate tailorable properties depending on MXene concentration, thus opening a library of ADA-GEL-MXene nanocomposite hydrogels. Moreover, the suitability of ADA-GEL-MXene hydrogels for 3D printing of grid-like scaffolds of up to 10 layers was shown. Additional 3D bioprinting studies demonstrated the applicability of the nanocomposite hydrogels as bioinks for 3D bioprinting of MG-63 osteoblast-like cells. Although the electrical conductivity was increased at higher MXene concentrations, compromised cell behavior was observed. This points to the conclusion that the concentration of MXene nanosheets must be carefully chosen depending on the required properties. Taken together, the presented ADA-GEL-MXene composite hydrogels exhibit significant potential for 3D bioprinting in bone tissue engineering and could be employed for the electrical stimulation of bone cells in the future.
导电水凝胶(ECHs)和电刺激有效调节成骨细胞附着、增殖和分化,从而引发骨组织再生。在这里,一种海藻酸二醛明胶(ADA-GEL)为基础的水凝胶被一种导电和成骨的2D纳米材料,即MXene修饰,以产生具有导电性的可降解和3D打印的纳米复合水凝胶。研究了MXene填料含量对水凝胶形貌、力学性能、电学性能、溶胀和降解性能的影响。结果表明,根据MXene浓度的不同,ADA-GEL-MXene纳米复合水凝胶具有不同的性能,从而建立了一个数据库。此外,ADA-GEL-MXene水凝胶适合3D打印多达10层的网格状支架。另外的3D生物打印研究证明了纳米复合水凝胶作为MG-63成骨细胞样细胞3D生物打印的生物墨水的适用性。虽然在较高的MXene浓度下电导率增加,但观察到细胞行为受损。这表明,MXene纳米片的浓度必须根据所需的性质仔细选择。综上所述,ADA-GEL-MXene复合水凝胶在骨组织工程的生物3D打印中显示出巨大的潜力,并可在未来用于骨细胞的电刺激。
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