Bioprinting最新文献_第10页

Development and characterization of bioinks for 3D bioprinting of in vitro skeletal muscle constructs 用于体外骨骼肌结构3D生物打印的生物墨水的开发和表征

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-31 DOI: 10.1016/j.bprint.2025.e00396

Rodi Kado Abdalkader , Kosei Yamauchi , Satoshi Konishi , Takuya Fujita

The use of 3D bioprinting to construct in vitro skeletal muscle models presents a promising approach; however, selecting an optimal bioink remains a common challenge. This study focuses on the development and characterization of bioinks for extrusion-based 3D bioprinting, specifically targeting the creation of accurate skeletal muscle models. By exploring various compositions of alginate, gelatin, fibrinogen, and nanofiber cellulose, we evaluate these formulations based on printability and their support for the growth and differentiation of C2C12 myoblast cells.

While alginate provided a strong, stable matrix for printing scaffolds embedded with C2C12 cells, it did not effectively promote cell growth and differentiation. The addition of fibrinogen to alginate enhanced cell growth and differentiation but was limited mainly to the scaffold surfaces, even with the inclusion of gelatin as a sacrificial ink. Notably, replacing alginate with nanofiber cellulose (NFC) alongside fibrinogen significantly improved cell growth and differentiation, leading to the formation of mature myotubes. Cell distribution was observed both inside and on the surfaces of the scaffolds, indicating effective spatial cell distribution. Furthermore, the scaffolds were tailored to form skeletal muscle bundles anchored between PDMS pillars for contractility testing. Upon exposure to electrical stimulation, the cells displayed measurable displacement, demonstrating contractile function.

These findings offer valuable insights into optimizing bioink formulations that promote myoblast growth and differentiation into skeletal muscle in vitro, with potential applications in future neuromuscular disease modeling.

利用生物3D打印技术构建体外骨骼肌模型是一种很有前途的方法；然而，选择一种最佳的生物链接仍然是一个共同的挑战。本研究的重点是基于挤压的生物3D打印的生物墨水的开发和表征，特别是针对精确的骨骼肌模型的创建。通过探索海藻酸盐、明胶、纤维蛋白原和纳米纤维纤维素的不同组成，我们评估了这些配方的可打印性及其对C2C12成肌细胞生长和分化的支持。海藻酸盐为C2C12细胞包埋的打印支架提供了坚固、稳定的基质，但不能有效促进细胞生长和分化。在海藻酸盐中加入纤维蛋白原可以促进细胞生长和分化，但主要局限于支架表面，即使加入明胶作为牺牲墨水也是如此。值得注意的是，用纳米纤维纤维素（NFC）和纤维蛋白原代替海藻酸盐显著改善了细胞生长和分化，导致成熟肌管的形成。在支架内部和表面均观察到细胞的分布，表明细胞的空间分布是有效的。此外，这些支架被定制成固定在PDMS支柱之间的骨骼肌束，用于收缩性测试。当受到电刺激时，这些细胞显示出可测量的位移，显示出收缩功能。这些发现为优化促进成肌细胞生长和向体外骨骼肌分化的生物链接配方提供了有价值的见解，在未来神经肌肉疾病建模中具有潜在的应用前景。

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引用次数: 0

3D printed cellulose nanofiber-reinforced and iron-crosslinked double network hydrogel composites for tissue engineering applications: Mechanical properties and cellular viability 用于组织工程应用的3D打印纤维素纳米纤维增强和铁交联双网水凝胶复合材料：机械性能和细胞活力

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-27 DOI: 10.1016/j.bprint.2025.e00392

Rohit Goyal , Soumyasri Nikhilesh Mahapatra , Rashmi Yadav , Santanu Mitra , Animesh Samanta , Anuj Kumar , Bimlesh Lochab

Additive manufacturing (i.e. 3D printing) is a promising technology for creating three-dimensional (3D) complex tissue-engineered hydrogel structures based on computer digital models resulting from patient-specific anatomical data of the organs. However, besides the printing process, it is worth studying the variation of individual components of the developed hydrogel composites to enable their suitability for tissue engineering. In this work, we shaped 3D printed multi-layered dual (UV- and Fe³⁺ ions)-crosslinked structures using hydrogel-inks composed of polyacrylamide (PAM), alginate (ALG), and cellulose nanofibres (CNFs). For extrusion, ALG in hydrogel precursor ink acted as a viscosity modifier owing to rapid gelation in the presence of low Ca²⁺ ions and CNF provided shear-thinning behavior. With the addition of optimal content of CNF (3 wt%), the mechanical properties of 3D printed composite hydrogel were enhanced and tuned using different fiber orientations. The maximum tensile stress of PAM/ALG_1.5/3CNF composite hydrogel is measured as ∼162 kPa, and maximum tensile toughness as ∼54 kJ/m³ supporting a good fracture resistance. Moreover, CNF-Fe³⁺ loaded 3D printed dual-networked composite hydrogels could disperse energy more efficiently and displayed maximum tensile stress as ∼285 kPa and maximum toughness as ∼200 kJ/m³. Further, In the current study, developed composite structures exhibited enhanced swelling ratio and thermal stability. In addition, finite element (FE) modelling was also exploited to analyze the novel anisotropic composite structures using efficient computational techniques. It is established that varying nanofiber content and fibrils orientation can be utilized to modulate the physicochemical, mechanical, and biological characteristics of printed structures. Overall, PAM/ALG_1.5/3CNF-Fe³⁺ printed composite structures present substantial stretchability, enhanced anisotropic mechanical and physicochemical properties with excellent cytocompatibility.

增材制造（即3D打印）是一种很有前途的技术，用于基于患者特定器官解剖数据产生的计算机数字模型创建三维（3D）复杂的组织工程水凝胶结构。然而，除了打印过程之外，值得研究的是所开发的水凝胶复合材料的单个组分的变化，以使其适合于组织工程。在这项工作中，我们使用由聚丙烯酰胺（PAM）、海藻酸盐（ALG）和纤维素纳米纤维（cnf）组成的水凝胶墨水，塑造了3D打印多层双（UV-和Fe3+离子）交联结构。对于挤压，水凝胶前驱体油墨中的ALG由于在低Ca2+离子存在下快速凝胶化而充当粘度调节剂，CNF提供剪切变薄行为。随着CNF的最佳含量（3wt %）的加入，3D打印复合水凝胶的力学性能得到了增强和调整，并采用不同的纤维取向。PAM/ALG1.5/3CNF复合水凝胶的最大拉伸应力为~ 162 kPa，最大拉伸韧性为~ 54 kJ/m3，具有良好的抗断裂性能。此外，负载CNF-Fe3+的3D打印双网络复合水凝胶可以更有效地分散能量，最大拉伸应力为~ 285 kPa，最大韧性为~ 200 kJ/m3。此外，在本研究中，开发的复合材料结构具有增强的膨胀率和热稳定性。此外，还利用有限元模型，利用高效的计算技术对新型各向异性复合材料结构进行了分析。研究表明，改变纳米纤维含量和原纤维取向可以调节打印结构的物理化学、力学和生物学特性。总体而言，PAM/ALG1.5/3CNF-Fe3+打印的复合材料结构具有良好的拉伸性能，增强的各向异性力学和物理化学性能，具有优异的细胞相容性。

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引用次数: 0

Innovations in 3D printing of magnesium alloys and composites for biodegradable biomedical devices 用于生物可降解生物医学设备的镁合金和复合材料的3D打印创新

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-24 DOI: 10.1016/j.bprint.2025.e00390

Aditya Nair , Shruti Gupta , Aboli Jangitwar , Balasubramanian Kandasubramanian

Magnesium is among the plentiful minerals present in natural sources, serving as a crucial macronutrient for the human body, with numerous studies validating its distinctive traits such as remarkable biocompatibility within the human system, diminished stress shielding, and proficient physical and chemical characteristics. These attributes are pivotal elements when employing the mineral in alloys and composites for the fabrication of biomedical components. One particular application involves the utilization of magnesium-based alloys and composites in the creation of coronary stents and bone implants. The ability to manufacture magnesium-based biomedical components with precision and reduced material wastage through additive manufacturing methods has prompted a transition away from the conventional manufacturing processes presently in use. This review aims to offer a thorough assessment of the application of additive manufacturing in producing magnesium alloys and composites for biomedical purposes. The paper comprises a comparative examination of the fabrication methods presently employed for the production of these alloys and composites, with a particular emphasis on various additive manufacturing techniques. Furthermore, it delves into the surface modification of additively manufactured implants, which has shown considerable improvements in biocompatibility and corrosion resistance, which are crucial parameters in the realm of biomedicine.

镁是天然存在的丰富矿物质之一，是人体重要的常量营养素，许多研究证实了它的独特特性，如在人体系统内的卓越生物相容性，减少应激屏蔽，以及精通的物理和化学特性。当在合金和复合材料中使用矿物用于制造生物医学部件时，这些属性是关键元素。镁基合金和复合材料在冠状动脉支架和骨植入物制造中的一个特殊应用。通过增材制造方法精确制造镁基生物医学部件并减少材料浪费的能力促使了目前使用的传统制造工艺的转变。本文综述了增材制造技术在生物医用镁合金及复合材料生产中的应用。本文对目前用于生产这些合金和复合材料的制造方法进行了比较研究，特别强调了各种增材制造技术。此外，它还深入研究了增材制造植入物的表面改性，该改性在生物相容性和耐腐蚀性方面显示出相当大的改善，这是生物医学领域的关键参数。

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引用次数: 0

Evolution of medical 3D printing, printable biomaterials, prosthetic and regenerative dental applications 医疗3D打印的发展，可打印生物材料，修复和再生牙科应用

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-23 DOI: 10.1016/j.bprint.2025.e00395

Mohammed Ahmed Alghauli , Rola Aljohani , Waad Aljohani , Shahad Almutairi , Ahmed Yaseen Alqutaibi

This review explores the rapid advancements in additive manufacturing, particularly 3D printing, within dentistry, focusing on bioprinting. It highlights the technology's efficiency, cost-effectiveness, and environmental sustainability while comprehensively analyzing its historical development, classification, and applications. The study compares additive manufacturing with conventional subtractive methods like CNC milling and evaluates the materials used. A thorough literature search across PubMed, Scopus, Web of Science, Cochrane, and Google Scholar was conducted, focusing on recent developments in 3D printing and CAD/CAM technologies in dentistry. The review identifies key applications, including surgical guides and root analog implants in implant dentistry, as well as the production of dental models, denture bases, and metal frameworks. Though prosthodontics is in the early stages of adopting 3D printing, advancements in materials and technologies are paving the way for its broader application. This review provides valuable insights for researchers and developers, emphasizing the potential of additive manufacturing to become a dominant chairside production method.

这篇综述探讨了增材制造的快速发展，特别是3D打印，在牙科领域，重点是生物打印。它强调了该技术的效率、成本效益和环境可持续性，同时全面分析了其历史发展、分类和应用。该研究将增材制造与传统的减法制造（如CNC铣削）进行了比较，并评估了所使用的材料。对PubMed、Scopus、Web of Science、Cochrane和b谷歌Scholar进行了全面的文献检索，重点关注牙科3D打印和CAD/CAM技术的最新发展。这篇综述确定了主要的应用，包括在种植牙科中的外科指导和牙根模拟种植体，以及牙模型、义齿基托和金属框架的生产。虽然口腔修复还处于采用3D打印的早期阶段，但材料和技术的进步正在为其更广泛的应用铺平道路。这篇综述为研究人员和开发人员提供了有价值的见解，强调了增材制造成为主导椅边生产方法的潜力。

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引用次数: 0

Fabrication of organ-on-a-chip using microfluidics 用微流体技术制造器官芯片

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-22 DOI: 10.1016/j.bprint.2025.e00394

S. Ying-Jin , I. Yuste , E. González-Burgos , D.R. Serrano

The use of microfluidic devices represents a significant advancement beyond conventional techniques in the development of innovative in vitro assays. Microfluidic chips are specialized devices that precisely control fluids at the microscale level through intricate microchannels, enabling the replication of physical and chemical conditions. When combined with tissue engineering, these chips have evolved into highly specialized tools known as Organ-on-a-Chip (OoC) devices, which can simulate the physiology and functionality of various human tissues and organs. OoC devices are cutting-edge technologies that integrate a biological component representing the target organ with a microfluidic component that mimics blood flow. This combination allows for the replication of biological structures with a more accurate representation of the in vivo physiological cellular microenvironment, which can be finely tuned by adjusting the flow rate and composition. As a result, novel microfluidic models for in vitro research can overcome the limitations of traditional 2D and 3D static cell cultures, enabling faster clinical translation and more precise predictions of the efficacy, safety, pharmacodynamics, and pharmacokinetics of new drugs. This review will discuss various techniques for fabricating OoCs and their applications in mimicking different physiological microenvironments.

微流控装置的使用代表了在创新体外检测发展中超越传统技术的重大进步。微流控芯片是通过复杂的微通道在微尺度上精确控制流体的专用设备，可以复制物理和化学条件。当与组织工程相结合时，这些芯片已经发展成为高度专业化的工具，称为器官芯片（OoC）设备，可以模拟各种人体组织和器官的生理和功能。OoC设备是一种尖端技术，它将代表目标器官的生物成分与模拟血液流动的微流体成分结合在一起。这种组合允许生物结构的复制，更准确地表示体内生理细胞微环境，这可以通过调节流速和组成来精细调节。因此，用于体外研究的新型微流体模型可以克服传统的2D和3D静态细胞培养的局限性，实现更快的临床翻译和更精确的新药疗效、安全性、药效学和药代动力学预测。本文将讨论各种制备OoCs的技术及其在模拟不同生理微环境中的应用。

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引用次数: 0

Multi-material 3D bioprinting of human stem cells to engineer complex human corneal structures with stroma and epithelium 人类干细胞的多材料3D生物打印工程复杂的人角膜结构与基质和上皮

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-21 DOI: 10.1016/j.bprint.2025.e00391

P. Puistola , S. Huhtanen , K. Hopia , S. Miettinen , A. Mörö , H. Skottman

Developing cost-effective and scalable multi-material bioprinting technologies that combine multiple cell types is crucial to produce biomimetic, complex human tissue substitutes and overcome the scarcity of transplantable tissues. These technological developments can revolutionize the treatment of several conditions currently dependent on donor tissues, such as corneal blindness. Here, corneal structures consisting of two layers, stroma and epithelium, were manufactured by extrusion-based 3D bioprinting. To take steps towards clinical translation of bioprinting, three clinically compatible hyaluronic acid based bioinks were combined with human adipose tissue and induced pluripotent stem cell derived cell types. Each of the three bioinks was customized to suit the needs of different cells and to provide mechanical stability for the bioprinted structure. Along with offering a 3D environment with excellent cytocompatibility, these bioprinted corneal structures facilitated cellular interactions and network formation, which are essential for creating functional tissue substitutes. Consequently, this study provides important insight on how to bring together the technical aspects of multi-material bioprinting as well as the biological relevance and scalability of the bioprinted constructs, advancing the field of additive manufacturing for clinical applications.

开发结合多种细胞类型的具有成本效益和可扩展的多材料生物打印技术对于生产仿生、复杂的人体组织替代品和克服可移植组织的稀缺性至关重要。这些技术的发展可以彻底改变目前依赖于供体组织的几种疾病的治疗，例如角膜失明。在这里，角膜结构由两层组成，间质和上皮，是通过挤压生物3D打印制造的。为了实现生物打印的临床转化，我们将三种临床兼容的透明质酸生物墨水与人类脂肪组织和诱导多能干细胞来源的细胞类型结合起来。三种生物墨水中的每一种都是定制的，以适应不同细胞的需要，并为生物打印结构提供机械稳定性。除了提供具有优异细胞相容性的3D环境外，这些生物打印的角膜结构促进了细胞相互作用和网络形成，这对于创建功能性组织替代品至关重要。因此，这项研究为如何将多材料生物打印的技术方面以及生物打印结构的生物学相关性和可扩展性结合在一起提供了重要的见解，推动了临床应用的增材制造领域。

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引用次数: 0

Adjusting degradation rate, mechanical properties and bioactivity of 3D-Printed biphasic calcium phosphate scaffolds by silk fibroin/ platelet-rich plasma lysate coating for regeneration of craniofacial bone defects 丝素蛋白/富血小板血浆裂解液包覆3d打印双相磷酸钙支架修复颅面骨缺损的降解率、力学性能和生物活性

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-21 DOI: 10.1016/j.bprint.2025.e00389

Samira Tajvar , Afra Hadjizadeh , Saeed Saber Samandari , Shohreh Mashayekhan

Despite many advances, reconstruction of craniofacial bone defects has faced many challenges due to their complex anatomy. For this purpose, in recent decades, researchers have focused on developing biomimetic and patient-specific engineered tissues. In this study, we developed scaffolds designed specifically for craniofacial bone defects, featuring optimal mechanical properties and degradation rates. To this end, porous scaffolds based on Na- and Mg-doped carbonated hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) were prepared using 3D printing. The printed scaffolds were then coated with silk fibroin (SF) and human platelet-rich plasma lysate (HPL). The degradation rate of the scaffolds was optimized in terms of HA to β-TCP ratio, pore size, and layers of the SF coating. Mechanical tests showed that the Young's modulus, compressive strength, and toughness of the scaffolds increased from 0.093 ± 0.006 GPa, 2.939 ± 0.54 MPa and 8.531 ± 1.092 MJ m⁻³ to 0.228 ± 0.029 GPa, 52.521 ± 5.29 MPa and 237.757 ± 18.754 MJ m⁻³ (P < 0.001), respectively by coating with SF. To investigate the regenerative potential of the scaffolds, the behavior of cultured mesenchymal stem cells (MSCs) derived from adipose tissue on the samples was evaluated. The results showed that treatment of scaffolds with HPL promoted cell viability and adhesion and alkaline phosphatase (ALP) activity, which makes biphasic calcium phosphate (BCP)/SF/HPL composite scaffolds promising bone substitutes.

颅面骨缺损由于其复杂的解剖结构，其重建面临着许多挑战。为此，近几十年来，研究人员一直致力于开发仿生和患者特异性工程组织。在这项研究中，我们开发了专门为颅面骨缺损设计的支架，具有最佳的力学性能和降解率。为此，采用3D打印技术制备了基于Na和mg掺杂的碳化羟基磷灰石（HA）和β-磷酸三钙（β-TCP）的多孔支架。然后用丝素蛋白（SF）和人富血小板血浆裂解液（HPL）包被打印的支架。从HA与β-TCP比、孔径、SF涂层层数等方面对支架的降解率进行优化。力学试验表明，支架的杨氏模量、抗压强度和韧性从0.093±0.006 GPa、2.939±0.54 MPa和8.531±1.092 MJ m - 3增加到0.228±0.029 GPa、52.521±5.29 MPa和237.757±18.754 MJ m - 3 (P <；0.001)，分别用SF涂层。为了研究支架的再生潜力，我们评估了脂肪组织中培养的间充质干细胞（MSCs）在样品上的行为。结果表明，用HPL处理支架可提高细胞活力、黏附力和碱性磷酸酶（ALP）活性，使双相磷酸钙(BCP)/SF/HPL复合支架具有良好的骨替代品前景。

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引用次数: 0

Anatomically accurate 3D printed prosthetic incus for ossicular chain reconstruction 解剖精确的3D打印假体砧骨用于听骨链重建

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-21 DOI: 10.1016/j.bprint.2025.e00393

Masoud Mohseni-Dargah , Christopher Pastras , Payal Mukherjee , Kai Cheng , Khosro Khajeh , Mohsen Asadnia

Middle ear disease often leads to ossicular erosion, impairing auditory function and frequently requiring ossicular chain reconstruction (OCR) for hearing restoration. Columella-type prostheses, commonly used in OCR, have shown limited success due to issues such as displacement and extrusion, highlighting the need for more effective solutions. This study introduces a 3D-printed prosthesis anatomically resembling the human incus bone, referred to as the titanium prosthetic incus, as a potential device for OCR. Utilising Finite Element Analysis (FEA), CT imaging, and 3D printing, the prosthesis was numerically evaluated, fabricated, and experimentally tested to assess its mechanical performance and anatomical fit. The prosthetic incus demonstrated ossicular vibration comparable to healthy control ears, effectively transmitting sound energy to the inner ear. The results revealed that the prosthetic incus offers superior sound transmission performance, particularly at low frequencies (below 1000 Hz), when compared to the PORP, with similar performance at higher frequencies. Additionally, the prosthetic incus has the potential to improve overall stability over traditional PORP devices, with a reduced risk of displacement due to its precise anatomical fitting. This study also suggests that the approach of contralateral imaging and individualised 3D printing enhances the customisation and accuracy of OCR procedures, potentially reducing operative time and improving long-term outcomes. Furthermore, the cost-effective nature of 3D printing makes this solution both clinically viable and scalable. This innovative technique holds promise for advancing OCR by providing a durable, patient-specific prosthetic option that enhances sound transmission and surgical success rates for patients with middle ear ossicular erosion.

中耳疾病常导致听骨侵蚀，听觉功能受损，经常需要听骨链重建（OCR）来恢复听力。通常用于OCR的小柱型假体由于移位和挤压等问题而显示出有限的成功，强调需要更有效的解决方案。本研究介绍了一种类似于人类砧骨的3d打印假体，称为钛假体砧骨，作为OCR的潜在设备。利用有限元分析（FEA）、CT成像和3D打印技术，对假体进行了数值评估、制造和实验测试，以评估其机械性能和解剖契合度。假体砧骨表现出与健康对照耳相当的听骨振动，有效地将声能传递到内耳。结果表明，与PORP相比，假体砧骨具有优越的声音传输性能，特别是在低频（低于1000 Hz）时，在高频时具有相似的性能。此外，与传统的PORP装置相比，假牙具有提高整体稳定性的潜力，由于其精确的解剖拟合，降低了移位的风险。该研究还表明，对侧成像和个性化3D打印的方法增强了OCR程序的定制和准确性，有可能减少手术时间并改善长期结果。此外，3D打印的成本效益使得该解决方案在临床上既可行又可扩展。这种创新的技术有望通过提供耐用的、患者特定的假体选择来推进OCR，提高中耳听骨侵蚀患者的声音传输和手术成功率。

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引用次数: 0

Improved alginate bio-ink by recombinant self-assembled cell-sized spider-silk inspired-biopolymer 用重组自组装细胞大小的蜘蛛丝启发生物聚合物改进海藻酸盐生物墨水

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-12 DOI: 10.1016/j.bprint.2025.e00387

Dean Robinson , Miriam Gubelbank , Ella Sklan , Tali Tavor Re'em

Alginate is a natural linear polysaccharide polymer that is extracted from brown seaweed. It is extensively used due to its biocompatibility, ease of handling in aqueous environments, and relatively low cost. Alginate easily forms a hydrogel when crosslinked with a bivalent ion such as calcium. However, alginate hydrogel exhibits low mechanical strength and is cell-inert, having no cell-matrix interactions. To address these limitations and enhance alginate's utility as a bioink for bioprinting, we developed a novel alginate matrix combined with spider- silk, known for its exceptional resilience, elasticity, and strength, as well as its capacity to facilitate cell attachment. The unique recombinant spider-silk biopolymer used in our study (SVX), is synthetically produced, and self-assembles into water-insoluble cell-sized particles that are limited by the cell size in the expression system. These are characterized by a sponge-like structure, and are both biocompatible and non-immunogenic.

Incorporating synthetic spider-silk into alginate significantly increased the hydrogel's viscosity and compression resilience compared to alginate alone. SVX-enriched alginate exhibited superior printability, characterized by a lower spreading ratio at reduced pressures that is favorable for cell printing. The SVX-enriched alginate also demonstrated higher consistency in spreading ratios across a range of setup conditions. Bioprinting of cells within the SVX-enriched alginate bioink resulted in more homogenous cultures with prolonged and higher cell viability, compared to the larger, more condensed spheroids with lower cell viability observed in alginate bioprinted constructs. These enhanced cell cultures in the SVX-enriched constructs can be attributed to the improved stability of the constructs as well as spider-silk-mediated cell adherence.

褐藻酸盐是从褐藻中提取的一种天然线状多糖聚合物。由于其生物相容性，易于在水环境中处理，以及相对较低的成本，它被广泛使用。当海藻酸盐与二价离子如钙交联时，很容易形成水凝胶。然而，海藻酸盐水凝胶表现出低机械强度和细胞惰性，没有细胞-基质相互作用。为了解决这些限制并增强海藻酸盐作为生物打印生物链接的效用，我们开发了一种新的海藻酸盐基质与蜘蛛丝结合，以其卓越的弹性，弹性和强度以及促进细胞附着的能力而闻名。在我们的研究中使用的独特的重组蜘蛛丝生物聚合物（SVX）是合成的，并且自组装成不溶于水的细胞大小的颗粒，受表达系统中细胞大小的限制。它们的特点是海绵状结构，具有生物相容性和非免疫原性。与单独的海藻酸盐相比，将合成蜘蛛丝掺入海藻酸盐中显著提高了水凝胶的粘度和压缩弹性。富含svx的海藻酸盐表现出优越的印刷性能，其特点是在减压下较低的扩散比，有利于细胞印刷。在一系列设置条件下，富含svx的海藻酸盐也表现出更高的扩散比一致性。细胞在富含svx的藻酸盐生物链接中进行生物打印，与在藻酸盐生物打印结构中观察到的更大、更凝聚的球体和更低的细胞活力相比，培养物更均匀，细胞活力更长，细胞活力更高。这些增强的细胞培养在svx富集的结构中可以归因于结构稳定性的提高以及蜘蛛丝介导的细胞粘附性。

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引用次数: 0

An alginate-cellulose based bioink mimics the viscoelastic features of the melanoma microenvironment and its influence on cell cycle and invasion 海藻酸盐-纤维素基生物链接模拟黑色素瘤微环境的粘弹性特征及其对细胞周期和侵袭的影响

Q1 Computer Science

Bioprinting

Pub Date : 2025-01-09 DOI: 10.1016/j.bprint.2024.e00384

Carolin Eckert , Sonja Schmidt , Jessica Faber , Rainer Detsch , Martin Vielreicher , Zan Lamberger , Philipp Stahlhut , Evelin Sandor , Tannaz Karimi , Rafael Schmid , Andreas Arkudas , Oliver Friedrich , Silvia Budday , Gregor Lang , Annika Kengelbach-Weigand , Anja Bosserhoff

Melanoma, an aggressive tumor from melanocytes, poses challenges despite recent therapeutic advances. Understanding molecular changes in its progression is crucial. Melanoma cells develop in the epidermis, then start spreading into the dermis– the first step of the invasive, progressive process. The dermis is composed of elastic (proteoglycans) and stabilizing (collagens) molecules. To overcome limitations of 2D-cell culture models, we established a 3D-bio-printed dermis model for the analysis of tumor cell features using a blend of alginate and microfibrillar cellulose. Testing different compositions in extrusion-based bioprinting confirmed good printability with high cell viability for AlgCell ink. Mechanical and optical analyses revealed dermis-like viscoelasticity and a pore size allowing nutrition supply and cell movement. We evaluated survival and proliferation of the cells and printed tumor spheroids and determined different migratory behavior comparing alginate to AlgCell. Interestingly, multiphoton microscopy revealed random cellulose fiber distribution around the spheroids after 7 days of cultivation with individual single cells, which had left the tumor spheroid and invaded into the microenvironment. Traditional 2D-models inadequately capture 3D mechanisms like invasion and migration. Our 3D-tumor model mimics the microenvironment, enabling in-depth analyses akin to in vivo conditions. This promises insights into tumor progression and testing of therapeutic interventions.

黑色素瘤是一种来自黑色素细胞的侵袭性肿瘤，尽管最近治疗取得了进展，但仍面临挑战。了解其发展过程中的分子变化是至关重要的。黑色素瘤细胞在表皮发育，然后开始向真皮扩散——这是侵入性进展过程的第一步。真皮由弹性（蛋白聚糖）和稳定（胶原）分子组成。为了克服2d细胞培养模型的局限性，我们使用海藻酸盐和微纤维纤维素的混合物建立了3d生物打印真皮模型，用于分析肿瘤细胞特征。在基于挤压的生物打印中测试不同的成分，证实了AlgCell墨水具有良好的打印性和高细胞活力。机械和光学分析揭示了真皮样的粘弹性和允许营养供应和细胞运动的孔径。我们评估了细胞和打印的肿瘤球体的存活和增殖，并确定了海藻酸盐和海藻细胞的不同迁移行为。有趣的是，在多光子显微镜下，单个单细胞培养7天后，纤维素纤维在球体周围随机分布，这些纤维已经离开肿瘤球体并侵入微环境。传统的2d模型不能充分捕捉入侵和迁移等3D机制。我们的3d肿瘤模型模拟微环境，使深入分析类似于体内条件。这有望深入了解肿瘤进展和测试治疗干预措施。

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