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3D and 4D printed materials for cardiac transplantation: Advances in biogenerative engineering 用于心脏移植的 3D 和 4D 打印材料:生物生成工程的进展
Q1 Computer Science Pub Date : 2024-10-12 DOI: 10.1016/j.bprint.2024.e00362
The most common reason for death worldwide is cardiovascular problems, and current treatments including medication, surgery, and heart transplants have disadvantages. Both 3D and 4D printing technologies are being investigated due to the demand for sophisticated solutions in cardiac care. With the use of these technologies, it may be possible to construct intricate circulatory systems, provide individualized care, and find solutions to problems like organ shortages and immune rejection. The paper focuses on various bioprinting methods that may be used in cardiac tissue engineering to create biomimetic structures, improve vascularization, and construct functional heart tissues using 3D and 4D manufacturing. The advancement of 3D and 4D printing procedures has led to substantial advancements in heart tissue engineering by offering precise and customized solutions. These technologies make it possible to fabricate intricate cardiovascular models along with medical equipment, which improves surgical planning and allows for patient-specific therapies. There are still challenges to be solved, primarily in the areas of realistic vascularization and the use of biomaterials that resemble natural cardiac tissue in terms of their mechanical and chemical properties. Technologies for 3D and 4D printing hold promise for resolving major issues with heart transplantation, namely donor scarcity and rejection. Improving vascularization along with biomaterial incorporation for therapeutic applications has to be the main goal of future research.
全球最常见的死亡原因是心血管问题,而目前的治疗方法包括药物、手术和心脏移植,但都存在缺陷。由于心脏护理领域对复杂解决方案的需求,3D 和 4D 打印技术正在接受研究。利用这些技术,有可能构建复杂的循环系统,提供个性化护理,并找到解决器官短缺和免疫排斥等问题的方法。本文重点介绍了可用于心脏组织工程的各种生物打印方法,以利用三维和四维制造技术创建生物仿生结构、改善血管化并构建功能性心脏组织。三维和四维打印技术的进步提供了精确和定制化的解决方案,从而大大推动了心脏组织工程的发展。这些技术使复杂的心血管模型和医疗设备的制造成为可能,从而改善了手术规划,实现了针对患者的治疗。目前仍有一些挑战有待解决,主要是在现实血管化和使用在机械和化学特性方面与天然心脏组织相似的生物材料方面。三维和四维打印技术有望解决心脏移植的主要问题,即供体稀缺和排斥反应。改善血管化并将生物材料纳入治疗应用必须成为未来研究的主要目标。
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引用次数: 0
Evolution of toxicity testing platforms from 2D to advanced 3D bioprinting for safety assessment of drugs 用于药物安全性评估的毒性测试平台从二维发展到先进的三维生物打印技术
Q1 Computer Science Pub Date : 2024-10-11 DOI: 10.1016/j.bprint.2024.e00363
The process involved in the discovery of novel drugs in medical sciences is challenging due to the time-intensive process that results in a high cost of development. Additionally, it is reported that 90 % of new drugs fail in clinical trials and cannot reach the market. One of the primary reasons for failure is that research laboratories and pharmaceutical companies have been relying exclusively on data derived from animal-based models for testing the efficacy and safety of newly developed drugs. These models do not completely recapitulate human physiology or pathophysiology, resulting in a lower translational rate. Further, the evaluation of toxicity of drugs to the human body requires a more robust and holistic approach. Researchers across the globe are focusing on developing in vitro3D models as alternatives to traditional animal testing to circumvent these challenges. These model systems could replicate and mimic the human physiological microenvironment, cellular interactions, and arrangements. In vitro3D models would provide improved methods to evaluate and comprehend drug response, thereby reducing the burden on animal usage. Further, reducing the time and costs associated with developing, screening, drug failure, and translation of drugs is also realizable. In this communication, existing in vitro 3D models that are used in the drug development process are reviewed. In addition, the advancements in using 3D bioprinting and organ-on-a-chip technologies towards generating human reconstructed tissues/organs are also highlighted. The challenges from a technological and regulatory perspective on adapting these alternate animal models are also discussed.
在医学科学领域,发现新药的过程具有挑战性,因为时间密集,开发成本高昂。此外,据报道,90% 的新药在临床试验中失败,无法进入市场。失败的主要原因之一是,研究实验室和制药公司一直完全依赖动物模型得出的数据来测试新开发药物的疗效和安全性。这些模型并不能完全再现人体生理或病理生理学,导致转化率较低。此外,评估药物对人体的毒性需要更强大、更全面的方法。全球研究人员正致力于开发体外 3D 模型,以替代传统的动物试验,从而规避这些挑战。这些模型系统可以复制和模拟人体生理微环境、细胞相互作用和排列。体外三维模型将为评估和理解药物反应提供更好的方法,从而减轻使用动物的负担。此外,减少与药物开发、筛选、药物失效和转化相关的时间和成本也是可以实现的。本文回顾了药物开发过程中使用的现有体外三维模型。此外,还重点介绍了利用三维生物打印和芯片器官技术生成人体重建组织/器官的进展。此外,还从技术和监管的角度讨论了采用这些替代动物模型所面临的挑战。
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引用次数: 0
Robust design optimization of Critical Quality Indicators (CQIs) of medical-graded polycaprolactone (PCL) in bioplotting 生物印染中医用级聚己内酯(PCL)关键质量指标(CQIs)的稳健优化设计
Q1 Computer Science Pub Date : 2024-10-05 DOI: 10.1016/j.bprint.2024.e00361
Polycaprolactone (PCL), either in its pure grade or as a polymeric matrix for bio-composites, plays a key role in the biomedical and bioengineering industries. It is also considered a multifunctional and versatile polymer for bioprinting and bioplotting purposes, especially in tissue engineering. Herein, an undiscovered yet valuable aspect of PCL extrusion-based bioprinting, such as the predictability of Critical Quality Indicators (CQIs), is investigated in depth. With the aid of the robust L25 orthogonal matrix design, the six most generic and device-independent control factors proved their impact on quality metrics such as global porosity, dimensional conformity, and surface roughness, determined with the aid of highly evolved Nondestructive Testing (NDT) and algorithms. To this end, 25 experimental runs were set, and 125 specimens were fabricated using an industrial-scale bio-plotter and medical-graded polycaprolactone. Various infill densities (ID), layer thicknesses (LT), raster deposition angles (RDA), printing speeds (PS), nozzle temperatures (NT), and bed temperatures (BT) were applied. CQIs were determined using optical profilometry and microscopy, and micro-computed tomography. Quadratic predictive equations were compiled and verified using two additional, well-chosen experimental runs. These generally applicable predictive models carry a massive amount of research and industrial merit, as they ensure visibility in bioprinting with PCL.
聚己内酯(PCL),无论是纯品还是作为生物复合材料的聚合物基质,都在生物医学和生物工程行业发挥着重要作用。它也被认为是一种多功能聚合物,可用于生物打印和生物制图,特别是在组织工程方面。本文深入研究了基于 PCL 挤压技术的生物打印技术中一个尚未发现但却很有价值的方面,如关键质量指标(CQIs)的可预测性。借助稳健的 L25 正交矩阵设计,六个最通用且与设备无关的控制因素证明了它们对全局孔隙率、尺寸一致性和表面粗糙度等质量指标的影响,这些指标是借助高度进化的无损检测(NDT)和算法确定的。为此,设定了 25 次实验运行,并使用工业规模的生物绘图仪和医用级聚己内酯制作了 125 个试样。实验中采用了不同的填充密度 (ID)、层厚 (LT)、光栅沉积角度 (RDA)、打印速度 (PS)、喷嘴温度 (NT) 和床层温度 (BT)。使用光学轮廓仪、显微镜和微型计算机断层扫描确定了 CQI。通过另外两次精心选择的实验运行,编制并验证了四元预测方程。这些普遍适用的预测模型具有巨大的研究和工业价值,因为它们确保了 PCL 生物打印的可见性。
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引用次数: 0
Recent advances in the development of stereolithography-based additive manufacturing processes: A review of applications and challenges 基于立体光刻技术的增材制造工艺的最新进展:应用与挑战综述
Q1 Computer Science Pub Date : 2024-09-26 DOI: 10.1016/j.bprint.2024.e00360
Additive manufacturing processes have progressed over recent years due to their superiority over conventional manufacturing methods. Their ability to fabricate materials with complex structures, increased precision, and reduced cost have opened avenues for various industrial applications, including biomedical, electrical, mechanical, aviation, and filtration, and led to their development over time. Stereolithography (SLA) is an additive manufacturing technique, through photopolymerization reaction, it solidifies a selective resin to produce three-dimensional objects. SLA has emerged as a leading 3D printing technique, revolutionizing prototyping and production across various industries. SLA has been through four generations of development and advancement, resulting in its improved performance, the diversity of materials, and the variety of applications. Stereolithography has diversified its material and emerged as a promising method for polymer-based composite when operating under optimized conditions. SLA offers superior resolution, high finish quality, improved speed and precision, and is cost-effective compared to alternative techniques like Fused Deposition Modeling (FDM). This current study aims to comprehensively review SLA development, its processes, applications and inherent challenges in mechanical, electrical and biomedical fields.
近年来,快速成型制造工艺因其优于传统制造方法而不断进步。它们能够制造结构复杂的材料,提高精度,降低成本,为生物医学、电气、机械、航空和过滤等各种工业应用开辟了道路,并促使其不断发展。立体光刻(SLA)是一种增材制造技术,它通过光聚合反应,固化选择性树脂来制造三维物体。SLA 已成为一种领先的 3D 打印技术,为各行各业的原型设计和生产带来了革命性的变化。立体光刻技术经历了四代的发展和进步,其性能不断提高,材料更加多样化,应用领域也更加广泛。立体光刻技术实现了材料的多样化,并在优化条件下成为聚合物基复合材料的一种有前途的方法。与熔融沉积建模(FDM)等替代技术相比,SLA 具有分辨率高、光洁度高、速度快、精度高、成本低等优点。本研究旨在全面回顾 SLA 的发展及其在机械、电气和生物医学领域的工艺、应用和固有挑战。
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引用次数: 0
Optimizing biomaterial inks: A study on the printability of Carboxymethyl cellulose-Laponite nanocomposite hydrogels and dental pulp stem cells bioprinting 优化生物材料墨水:羧甲基纤维素-皂石纳米复合水凝胶和牙髓干细胞生物打印的可打印性研究
Q1 Computer Science Pub Date : 2024-09-18 DOI: 10.1016/j.bprint.2024.e00358

Tissue engineering approaches require biocompatible materials with precise pre-designed geometry, shape fidelity, and promote cellular functions. Addressing these requirements, our study focused on developing an optimized bioink formulation using carboxymethyl cellulose (CMC) and Laponite hydrogels tailored for extrusion-based three-dimensional bioprinting. To this, we investigated the rheological properties and filament behavior before and during printing. As Laponite concentration increased in CMC solutions, it improved shear-thinning behavior, viscosity, and storage modulus, resulting in well-defined filament characteristics with lower diffusion rates, excellent shape fidelity, and robust printability. Thus, we achieved a suitable biomaterial ink formulation with concentrations of 1 wt% of CMC and 4 wt% of Laponite (1C4L). Subsequently, a statistical analysis guided us to select the optimal parameters for large-scale construct printing: a nozzle speed of 5 mm/s, a print distance of 0.41 mm, and an extrusion multiplier of 1.35. After that, we enhanced the structural integrity of printed hydrogels through ionic crosslinking with calcium chloride (CaCl2) and citric acid (CA), revealing higher-strength hydrogels at higher concentrations of CaCl2. Finally, we have confirmed the groundbreaking potential of our bioink by integrating dental pulp mesenchymal stem cells (DPSC) into the 1C4L ink. Our bioprinted constructs showed optimized swelling, non-toxic effects, and retained excellent shape fidelity, crucial for creating anatomically accurate tissues. Our findings provide crucial insights linking the rheological analysis, the bioprinting process, and the biological properties of hydrogels, paving the way for their use for tissue engineering and other biomedical applications.

组织工程方法要求生物相容性材料具有精确的预设计几何形状、形状保真度和促进细胞功能。为了满足这些要求,我们的研究重点是利用羧甲基纤维素(CMC)和皂石水凝胶开发一种优化的生物墨水配方,以适应基于挤压的三维生物打印。为此,我们研究了打印前和打印过程中的流变特性和长丝行为。随着皂石在 CMC 溶液中浓度的增加,它改善了剪切稀化行为、粘度和存储模量,从而产生了具有较低扩散率、出色的形状保真度和稳健的打印性的定义明确的长丝特性。因此,我们获得了浓度为 1 wt% 的 CMC 和 4 wt% 的皂石(1C4L)的合适生物材料墨水配方。随后,在统计分析的指导下,我们选择了大规模构造打印的最佳参数:喷嘴速度为 5 毫米/秒,打印距离为 0.41 毫米,挤出倍率为 1.35。之后,我们通过氯化钙(CaCl2)和柠檬酸(CA)的离子交联增强了打印水凝胶的结构完整性,发现CaCl2浓度越高,水凝胶强度越高。最后,通过将牙髓间充质干细胞(DPSC)整合到 1C4L 墨水中,我们证实了生物墨水的突破性潜力。我们的生物打印构建体显示出优化的溶胀、无毒效果,并保持了极佳的形状保真度,这对于创建解剖精确的组织至关重要。我们的研究结果为流变分析、生物打印过程和水凝胶的生物特性之间的联系提供了重要的见解,为将其用于组织工程和其他生物医学应用铺平了道路。
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引用次数: 0
Precision 3D printing of chitosan-bioactive glass inks: Rheological optimization for enhanced shape fidelity in tissue engineering scaffolds 壳聚糖生物活性玻璃油墨的精密三维打印:流变学优化提高组织工程支架的形状保真度
Q1 Computer Science Pub Date : 2024-09-18 DOI: 10.1016/j.bprint.2024.e00359
3D printing technology in tissue engineering applications provides several advantages for scaffold development, especially with natural materials, such as chitosan, which provides a biomimetic environment for cellular growth. However, chitosan hydrogel-based inks still show poor printing fidelity. In this article, we overcame this challenge by incorporating bioactive glasses (BG) nanoparticles (up to 5 wt%) into the chitosan hydrogel. The resulting inks were characterized by rheological tests, while their processability was evaluated through measurements of shape fidelity. An indirect cytotoxicity assay was also conducted to evaluate the cell viability of the printed scaffolds. The results indicated that adding BG nanoparticles to the chitosan-based ink modified its rheological properties and improved its shape-fidelity during 3D printing, which we suggest are consequences of hydrogen bonds established between the glass and the chitosan chains. Also, cytotoxicity assessment demonstrated that the resulting scaffold exhibits high cell viability. In conclusion, the proposed composite ink has optimized rheological properties for 3D printing and is promising for applications in tissue engineering.
组织工程应用中的三维打印技术为支架开发提供了多种优势,尤其是天然材料,如壳聚糖,它能为细胞生长提供仿生环境。然而,基于壳聚糖水凝胶的油墨仍然显示出较低的打印保真度。在本文中,我们通过在壳聚糖水凝胶中加入生物活性玻璃 (BG) 纳米颗粒(最多 5 wt%)来克服这一难题。我们通过流变学测试对所得油墨进行了表征,并通过形状保真度测量对其加工性进行了评估。此外,还进行了间接细胞毒性试验,以评估印刷支架的细胞活力。结果表明,在壳聚糖基墨水中添加 BG 纳米粒子可改变其流变特性,并改善其在 3D 打印过程中的形状保真度,我们认为这是玻璃和壳聚糖链之间建立氢键的结果。此外,细胞毒性评估表明,生成的支架具有很高的细胞活力。总之,所提出的复合油墨具有优化的三维打印流变特性,有望应用于组织工程。
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引用次数: 0
Recent advancements and challenges in 3D bioprinting for cancer applications 三维生物打印在癌症应用领域的最新进展和挑战
Q1 Computer Science Pub Date : 2024-09-13 DOI: 10.1016/j.bprint.2024.e00357

3D bioprinting has emerged as a promising technology with transformative potential in cancer research and therapy. This review explores the innovative applications, challenges, and future directions of 3D bioprinting in the field of cancer. By recapitulating tumor microenvironments and heterogeneity, 3D bioprinted models offer valuable platforms for studying cancer biology, drug responses, and personalized medicine. The integration of 3D bioprinting with other cutting-edge technologies, such as organ-on-a-chip and microfluidics, has further enhanced the ability to replicate the dynamic and heterogeneous nature of tumors. The forthcoming paths include advancements in biomaterial engineering, bioprinting techniques, and interdisciplinary collaborations to overcome these challenges. Integration of 3D bioprinting into clinical practice holds promise for revolutionizing cancer diagnosis, treatment, and management.

三维生物打印已成为一项前景广阔的技术,在癌症研究和治疗方面具有变革潜力。本综述探讨了三维生物打印技术在癌症领域的创新应用、挑战和未来发展方向。通过再现肿瘤微环境和异质性,三维生物打印模型为研究癌症生物学、药物反应和个性化医疗提供了宝贵的平台。三维生物打印与其他尖端技术(如芯片上器官和微流控技术)的整合进一步增强了复制肿瘤动态和异质性的能力。未来的发展方向包括生物材料工程、生物打印技术和跨学科合作方面的进步,以克服这些挑战。将三维生物打印技术融入临床实践,有望彻底改变癌症诊断、治疗和管理。
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引用次数: 0
Advanced additive manufacturing in implant dentistry: 3D printing technologies, printable materials, current applications and future requirements 种植牙领域的先进增材制造技术:三维打印技术、可打印材料、当前应用和未来需求
Q1 Computer Science Pub Date : 2024-08-24 DOI: 10.1016/j.bprint.2024.e00356

The utilization of 3D printing technologies is extensively pervasive across diverse sectors, including design, engineering, and manufacturing. These sophisticated manufacturing techniques depend on digitally designed models to autonomously construct 3D objects. With the growing interest in 3D printing within dentistry, specifically regarding dental implants, there has been a rapid dissemination of information pertaining to this domain and its applications. As a result, it has become crucial to conduct a comprehensive review on this topic. 3D printing technologies have played a pivotal role in oral implantology. This review provides a comprehensive analysis of the current state and future needs of 3D printing in implant dentistry, covering technologies, printable materials, and applications in both the surgical and prosthodontic stages of dental implant therapy. Furthermore, it discusses considerations for choosing the appropriate 3D printing technology for specific dental applications. This comprehensive examination offers key insights into the progress, practical uses, and future prospects of 3D printing in dental implants.

三维打印技术的应用广泛渗透到设计、工程和制造等各个领域。这些复杂的制造技术依赖于数字化设计的模型来自主构建三维物体。随着牙科领域对 3D 打印技术的兴趣日益浓厚,特别是在牙科植入物方面,与这一领域及其应用相关的信息得到了迅速传播。因此,对这一主题进行全面回顾变得至关重要。3D 打印技术在口腔种植学中发挥了举足轻重的作用。本综述全面分析了 3D 打印技术在种植牙领域的现状和未来需求,涵盖了种植牙治疗手术和修复阶段的技术、可打印材料和应用。此外,它还讨论了为特定牙科应用选择适当 3D 打印技术的注意事项。这本全面的研究报告提供了有关 3D 打印技术在牙科种植方面的进展、实际应用和未来前景的重要见解。
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引用次数: 0
A review of current state-of-the-art materiobiology and technological approaches for liver tissue engineering 综述当前最先进的肝脏组织工程材料生物学和技术方法
Q1 Computer Science Pub Date : 2024-08-23 DOI: 10.1016/j.bprint.2024.e00355

Chronic liver disease and related disorders are responsible for millions of deaths each year worldwide. In clinical practice, liver transplantation is recognized as an effective means of saving the lives of patients with severe complications. The shortage of organ donors has necessitated the development of bioengineered therapies that promote regeneration of the defective site and the creation of closely mimicking in vitro models for early prediction of disease states, hepatotoxicity testing, and accurate diagnostics. Despite tremendous research efforts, bioengineering of fully functional livers, detailed information on rare pathological mechanisms, and reliable bioartificial tissue-based therapies remain limited. On the other hand, 2D monolayer culture techniques are too simple to mimic and reproduce the functional characteristics of the liver accurately, its structural microenvironment, and the dynamic situation of cells in vivo. Therefore, tissue engineering-based 3D constructs outperform 2D culture systems. In this review, we provide insight into liver-related health complications, and the use of different cell types for tissue engineering. We also assess the current state of materiobiology and bioengineering technologies for fabricating 3D constructs. Afterward, we highlight the recent progress in liver tissue engineering, and outline the most relevant studies applying co-culture systems, spheroids, and organoid approaches, microfluidics, and 3D-bioprinting techniques. Finally, current dilemmas and possible future directions are explored.

全世界每年有数百万人死于慢性肝病和相关疾病。在临床实践中,肝移植被认为是挽救严重并发症患者生命的有效手段。由于器官捐献者的短缺,有必要开发生物工程疗法,以促进缺损部位的再生,并建立密切模仿的体外模型,用于疾病状态的早期预测、肝毒性测试和准确诊断。尽管开展了大量研究工作,但全功能肝脏的生物工程、罕见病理机制的详细信息以及可靠的生物人工组织疗法仍然有限。另一方面,二维单层培养技术过于简单,无法准确模拟和再现肝脏的功能特征、结构微环境和体内细胞的动态情况。因此,基于组织工程学的三维构建体优于二维培养系统。在这篇综述中,我们深入探讨了与肝脏相关的健康并发症,以及不同类型细胞在组织工程中的应用。我们还评估了用于制造三维构建体的材料生物学和生物工程技术的现状。随后,我们重点介绍了肝脏组织工程的最新进展,并概述了应用共培养系统、球形和类器官方法、微流体技术和三维生物打印技术的最相关研究。最后,我们探讨了当前的困境和未来可能的发展方向。
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引用次数: 0
Enhancing mechanical performance of solvent-cast 3D printed PCL composites: A comprehensive optimization approach 提高溶剂铸造 3D 打印 PCL 复合材料的机械性能:综合优化方法
Q1 Computer Science Pub Date : 2024-08-14 DOI: 10.1016/j.bprint.2024.e00354

This study aims to enhance the mechanical properties of 3D-printed scaffolds by optimizing a composite of Poly-ε-caprolactone (PCL), poly-hydroxybutyrate (PHB), and synthetic fluorapatite (FHAp) using Response Surface Methodology (RSM). The research targets the intricate relationships between PCL, PHB, and FHAp concentrations, crucial for achieving optimal tensile, compressive, and flexural strengths. The solvent-cast process successfully yielded FHAp-reinforced PCL composites, confirmed by XRD and FTIR spectra. The findings indicate that an optimal PHB content of over 15 % wt/v and PCL under 10 % wt/v significantly enhance tensile strength, achieving values up to 48 MPa. Compressive strength peaked at PHB concentrations of 13–16 % wt/v and PCL concentrations of 9–13 % wt/v, showcasing effective stress transmission, with the highest recorded value being 90 MPa. Flexural strength exceeded 100 MPa with lower concentrations of PCL and PHB, emphasizing the need for a balance of rigidity and flexibility. The study identifies the optimum composition for these mechanical properties at PCL 9.432 % wt/v, PHB 16.568 % wt/v, and FHAp 24.933 % wt/v, crucial for advanced biomedical implant applications.

本研究旨在利用响应面方法学(RSM)优化聚ε-己内酯(PCL)、聚羟基丁酸酯(PHB)和合成氟磷灰石(FHAp)的复合材料,从而提高三维打印支架的机械性能。研究的目标是 PCL、PHB 和 FHAp 浓度之间的复杂关系,这对获得最佳拉伸、压缩和弯曲强度至关重要。经 XRD 和傅立叶变换红外光谱证实,溶剂浇铸工艺成功制备出了 FHAp 增强 PCL 复合材料。研究结果表明,PHB 的最佳含量超过 15 % wt/v,PCL 的最佳含量低于 10 % wt/v,可显著提高拉伸强度,最高可达 48 兆帕。抗压强度在 PHB 浓度为 13-16 % wt/v 和 PCL 浓度为 9-13 % wt/v 时达到峰值,显示出有效的应力传递,最高记录值为 90 兆帕。当 PCL 和 PHB 的浓度较低时,挠曲强度超过 100 兆帕,强调了刚柔平衡的必要性。研究确定了 PCL 9.432 % wt/v、PHB 16.568 % wt/v 和 FHAp 24.933 % wt/v 这些机械性能的最佳成分,这对于先进的生物医学植入应用至关重要。
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引用次数: 0
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