bioink

生物墨水
  • 文章类型: Journal Article
    肿瘤模型的出现极大地促进了治疗药物和方法的发展。然而,由于其固有的复杂性,建立一个可以完全复制肿瘤组织情况的模型仍然极具挑战性。随着组织工程学的发展,生物打印技术的进步促进了肿瘤模型的升级。本文重点介绍生物打印的最新进展,特别强调3D肿瘤模型的构建,并强调了这两种技术的集成。此外,它讨论了相关技术的挑战和未来方向,同时还强调通过类似于体外器官的3D肿瘤模型的出现来有效地重建肿瘤微环境,从而加速新的抗癌疗法的发展。
    The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.
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  • 文章类型: Journal Article
    作为一种新兴的制造技术,三维(3D)生物打印为多面性和复杂的功能整合架构的仿生构建提供了潜力,特别是功能性仿生真皮结构,包括皮肤附件。尽管具有完整生物活性和生理功能的组织工程皮肤仍无法制造,据信,随着基质材料的进步,成型工艺,和生物技术,新一代的生理活性皮肤将在未来诞生。为了让参与相关研究的读者和研究人员对3D打印组织工程皮肤有一个系统和全面的了解,本文对当前的研究环境进行了注释,强大的障碍,以及组织工程皮肤中即将出现的轨迹,包括:(1)普遍的生物材料(胶原蛋白,壳聚糖,琼脂糖,海藻酸盐,等。)常规用于组织工程皮肤,并对各自的优点进行了辨别分析和比较,记过,和固有特征;(2)组织工程皮肤制造中使用的各种当前打印方法的基本原理和区别属性;(3)组织工程仿生皮肤领域的研究现状和进展;(4)对组织工程皮肤的现有研究进行细致的审查和总结,以确定当前的挑战和问题。
    As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues.
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  • 文章类型: Journal Article
    有效的沟通对于3R生物医学研究和临床前测试中替代方法的广泛接受和适用性至关重要。3D生物打印用于构建复杂的生物结构,以实现功能性肝脏模型,专门设计用于作为药物筛选的替代模型,毒理学调查,和组织工程。尽管在这个新兴领域的评论越来越多,一项全面的研究,缺乏系统评估生物打印肝脏模型的实践和报告质量。
    在这篇系统范围审查中,我们系统地搜索了MEDLINE(Ovid),EMBASE(Ovid)和BioRxiv在6月2日之前发表的研究,2022年。我们提取了关于方法论行为的数据,应用生物墨水,印刷模型的组成,进行实验和模型应用。对记录进行资格筛选,并由两名独立审稿人从专门从事生物打印和肝脏生物学的七个领域专家组成的小组中提取数据。我们使用RAYYAN进行筛选过程,使用SyRF进行数据提取。我们用R做数据分析,和R和GraphpadPRISM用于可视化。
    通过我们系统的数据库搜索,我们确定了1042条记录,其中63项符合纳入本系统范围审查的资格标准.我们的研究结果表明,基于挤出的印刷,结合由天然成分组成的生物墨水,成为肝脏模型生物打印中的主要打印技术。值得注意的是,HepG2肝癌细胞系是最常用的肝细胞类型,尽管公认的局限性。此外,51%的打印模型具有与非实质细胞的共培养,以增强其复杂性。纳入的研究提供了各种表征这些肝脏模型的技术,其主要应用主要集中在毒性测试。在经常分析的肝脏标志物中,白蛋白和尿素脱颖而出。此外,细胞色素P450(CYP)亚型,主要是CYP3A和CYP1A,被评估,并选择使用核受体激动剂诱导CYP活性的研究。
    我们的系统范围审查提供了基于证据的概述和生物打印肝脏模型研究现状的评估,代表了一种有前途的创新技术,用于创建替代器官模型。我们对模型开发的方法和技术方面进行了全面检查,并仔细检查了生物打印肝脏模型领域的报告质量。这种系统的范围审查可以作为一个有价值的模板,用于系统地评估器官模型开发在各种其他领域的进展。这里提供的透明衍生证据可以为研究界提供必要的支持,促进技术进步的适应,标准的建立,增强了模型的鲁棒性。这一点尤为重要,因为我们致力于建立新的方法作为动物试验的可靠替代品的长期目标,具有广泛和通用的应用。
    UNASSIGNED: Effective communication is crucial for broad acceptance and applicability of alternative methods in 3R biomedical research and preclinical testing. 3D bioprinting is used to construct intricate biological structures towards functional liver models, specifically engineered for deployment as alternative models in drug screening, toxicological investigations, and tissue engineering. Despite a growing number of reviews in this emerging field, a comprehensive study, systematically assessing practices and reporting quality for bioprinted liver models is missing.
    UNASSIGNED: In this systematic scoping review we systematically searched MEDLINE (Ovid), EMBASE (Ovid) and BioRxiv for studies published prior to June 2nd, 2022. We extracted data on methodological conduct, applied bioinks, the composition of the printed model, performed experiments and model applications. Records were screened for eligibility and data were extracted from included articles by two independent reviewers from a panel of seven domain experts specializing in bioprinting and liver biology. We used RAYYAN for the screening process and SyRF for data extraction. We used R for data analysis, and R and Graphpad PRISM for visualization.
    UNASSIGNED: Through our systematic database search we identified 1042 records, from which 63 met the eligibility criteria for inclusion in this systematic scoping review. Our findings revealed that extrusion-based printing, in conjunction with bioinks composed of natural components, emerged as the predominant printing technique in the bioprinting of liver models. Notably, the HepG2 hepatoma cell line was the most frequently employed liver cell type, despite acknowledged limitations. Furthermore, 51% of the printed models featured co-cultures with non-parenchymal cells to enhance their complexity. The included studies offered a variety of techniques for characterizing these liver models, with their primary application predominantly focused on toxicity testing. Among the frequently analyzed liver markers, albumin and urea stood out. Additionally, Cytochrome P450 (CYP) isoforms, primarily CYP3A and CYP1A, were assessed, and select studies employed nuclear receptor agonists to induce CYP activity.
    UNASSIGNED: Our systematic scoping review offers an evidence-based overview and evaluation of the current state of research on bioprinted liver models, representing a promising and innovative technology for creating alternative organ models. We conducted a thorough examination of both the methodological and technical facets of model development and scrutinized the reporting quality within the realm of bioprinted liver models. This systematic scoping review can serve as a valuable template for systematically evaluating the progress of organ model development in various other domains. The transparently derived evidence presented here can provide essential support to the research community, facilitating the adaptation of technological advancements, the establishment of standards, and the enhancement of model robustness. This is particularly crucial as we work toward the long-term objective of establishing new approach methods as reliable alternatives to animal testing, with extensive and versatile applications.
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  • 文章类型: Journal Article
    透明质酸(HA)广泛分布于人体结缔组织中,其独特的生物学和物理化学特性以及促进生物结构修复的能力使其成为组织再生和生物医学工程领域三维(3D)生物打印的有希望的候选者。此外,HA因其组织相容性而成为组织工程中生物墨水的理想原料,非免疫原性,生物降解性,抗炎特性,抗血管生成特性,和可修改性。组织工程是一个多学科领域,专注于哺乳动物组织的体外重建,如软骨组织工程,神经组织工程,皮肤组织工程,以及其他需要进一步临床应用的领域。在这次审查中,我们首先描述修改方法,交联方法,以及将HA及其衍生物作为生物墨水的生物打印策略,然后批判性地讨论其优势,缺点,每种方法的可行性。随后,我们回顾了HA生物墨水在3D生物打印中的实际临床应用和结果。最后,我们描述了HA生物墨水开发中的挑战和机遇,以提供进一步的研究参考和见解。
    Hyaluronic acid (HA) is widely distributed in human connective tissue, and its unique biological and physicochemical properties and ability to facilitate biological structure repair make it a promising candidate for three-dimensional (3D) bioprinting in the field of tissue regeneration and biomedical engineering. Moreover, HA is an ideal raw material for bioinks in tissue engineering because of its histocompatibility, non-immunogenicity, biodegradability, anti-inflammatory properties, anti-angiogenic properties, and modifiability. Tissue engineering is a multidisciplinary field focusing on in vitro reconstructions of mammalian tissues, such as cartilage tissue engineering, neural tissue engineering, skin tissue engineering, and other areas that require further clinical applications. In this review, we first describe the modification methods, cross-linking methods, and bioprinting strategies for HA and its derivatives as bioinks and then critically discuss the strengths, shortcomings, and feasibility of each method. Subsequently, we reviewed the practical clinical applications and outcomes of HA bioink in 3D bioprinting. Finally, we describe the challenges and opportunities in the development of HA bioink to provide further research references and insights.
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  • 文章类型: Journal Article
    心肌梗塞是全世界死亡率和发病率的主要原因之一。目前可用的治疗方案面临许多缺点,因此心脏组织工程,旨在对功能性心脏组织进行生物工程,用于组织修复,患者特异性药物筛选和疾病建模,正在探索作为一种可行的替代方案。为了实现这一点,细胞的适当组合,仿生支架模仿天然组织的结构和功能,和信号,是必要的。在脚手架制造技术中,三维打印,这是一种增材制造技术,能够将计算机辅助设计转化为3D对象,已经成为一种有前途的技术,可以开发具有高度定义架构的心脏贴片。作为复制复杂组织的又一步,例如心脏组织,最近,3D生物打印已经成为一种不仅打印生物材料的尖端技术,同时也有多种细胞类型。就生物墨水而言,从天然来源分离的生物材料是有利的,因为它们可以提供卓越的生物相容性和生物活性,从而促进所需的细胞反应。理想的仿生心脏贴片应包含额外的功能特性,这可以通过适当的功能化策略来实现。这些是复制天然组织所必需的,比如生化信号的释放,免疫调节特性,电导率,增强血管形成和形状记忆效应。该综述的目的是概述有关仿生3D打印基于天然生物材料的心脏贴片的开发的当前技术水平,描述3D打印制造方法,基于天然生物材料的生物墨水,功能化策略,以及在体外和体内的应用。
    Myocardial infarction is one of the major causes of mortality as well as morbidity around the world. Currently available treatment options face a number of drawbacks, hence cardiac tissue engineering, which aims to bioengineer functional cardiac tissue, for application in tissue repair, patient specific drug screening and disease modeling, is being explored as a viable alternative. To achieve this, an appropriate combination of cells, biomimetic scaffolds mimicking the structure and function of the native tissue, and signals, is necessary. Among scaffold fabrication techniques, three-dimensional printing, which is an additive manufacturing technique that enables to translate computer-aided designs into 3D objects, has emerged as a promising technique to develop cardiac patches with a highly defined architecture. As a further step toward the replication of complex tissues, such as cardiac tissue, more recently 3D bioprinting has emerged as a cutting-edge technology to print not only biomaterials, but also multiple cell types simultaneously. In terms of bioinks, biomaterials isolated from natural sources are advantageous, as they can provide exceptional biocompatibility and bioactivity, thus promoting desired cell responses. An ideal biomimetic cardiac patch should incorporate additional functional properties, which can be achieved by means of appropriate functionalization strategies. These are essential to replicate the native tissue, such as the release of biochemical signals, immunomodulatory properties, conductivity, enhanced vascularization and shape memory effects. The aim of the review is to present an overview of the current state of the art regarding the development of biomimetic 3D printed natural biomaterial-based cardiac patches, describing the 3D printing fabrication methods, the natural-biomaterial based bioinks, the functionalization strategies, as well as the in vitro and in vivo applications.
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  • 文章类型: Journal Article
    受损组织或器官的修复和再生是生物医学的主要挑战。以及新兴的3D生物打印技术,作为生物医学研究中的一类有前途的技术,用于组织工程和再生医学的发展。基于壳聚糖的生物墨水,作为天然生物材料,由于其独特的动态可逆性和出色的生物学特性,被认为是3D生物打印设计和制造各种支架的理想材料。我们的综述旨在为体外组织修复和再生提供基于壳聚糖的生物墨水的概述。从影响这些生物打印过程的壳聚糖改性开始。此外,我们总结了壳聚糖基生物墨水在各种3D打印策略中的应用进展。此外,讨论了壳聚糖基生物墨水的生物医学应用,主要集中在再生医学和组织建模工程。最后,讨论了该领域当前的挑战和未来的机遇。基于壳聚糖的生物墨水和3D生物打印的结合将有望开发用于组织或器官修复和再生的新型生物医学支架。
    The repair and regeneration of the injured tissues or organs is a major challenge for biomedicine, and the emerging 3D bioprinting technology as a class of promising techniques in biomedical research for the development of tissue engineering and regenerative medicine. Chitosan-based bioinks, as the natural biomaterials, are considered as ideal materials for 3D bioprinting to design and fabricate the various scaffold due to their unique dynamic reversibility and fantastic biological properties. Our review aims to provide an overview of chitosan-based bioinks for in vitro tissue repair and regeneration, starting from modification of chitosan that affect these bioprinting processes. In addition, we summarize the advances in chitosan-based bioinks used in the various 3D printing strategies. Moreover, the biomedical applications of chitosan-based bioinks are discussed, primarily centered on regenerative medicine and tissue modeling engineering. Finally, current challenges and future opportunities in this field are discussed. The combination of chitosan-based bioinks and 3D bioprinting will hold promise for developing novel biomedical scaffolds for tissue or organ repair and regeneration.
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  • 文章类型: Journal Article
    3D生物打印能够快速生成基于人类的小规模组织模型,或类器官,病理学建模,诊断,和药物开发。随着3D生物打印技术的使用,3D功能复杂组织可以通过结合生物相容性材料来创建,细胞,和生长因子。在当今世界,3D生物打印可能是满足器官移植需求的最佳解决方案。重要的是检查现有的文献,目的是确定3D生物打印应用的未来趋势。不同的生物打印技术,和研究人员选择的组织,考察现有文献是非常重要的。为了发现3D生物打印研究的趋势,这项工作对3D生物打印进行了系统的文献综述。
    该文献对从Scopus数据库中提取的2000年至2022年生物打印研究文章进行了彻底的研究和分析。选择进行分析的文章根据发表年份进行分类,文章和出版商,nation,在生物打印领域工作的作者,大学,使用的生物材料,和有针对性的应用。
    顶级国家,大学,期刊,出版商,在分析了有关生物打印的研究出版物后,选出了该领域的作家。在这项研究中,还确定了研究主题和研究趋势。此外,已经观察到,需要在该领域进行额外的研究,以开发生物墨水及其特性,这些特性可以指导从业者和研究人员,同时选择适当的生物材料组合以获得适合模仿人体组织的生物墨水。
    这项研究包括研究结果,recommendations,以及对生物打印研究人员和从业人员的观察。本文列出了重大的研究空白,未来的研究方向,以及生物打印的潜在应用领域。
    此处进行的审查主要集中在收集过程中,组织,捕获,评估,和分析数据,以更深入地了解生物打印,并确定潜在的未来研究趋势。
    UNASSIGNED: 3D bioprinting is capable of rapidly producing small-scale human-based tissue models, or organoids, for pathology modeling, diagnostics, and drug development. With the use of 3D bioprinting technology, 3D functional complex tissue can be created by combining biocompatible materials, cells, and growth factor. In today\'s world, 3D bioprinting may be the best solution for meeting the demand for organ transplantation. It is essential to examine the existing literature with the objective to identify the future trend in terms of application of 3D bioprinting, different bioprinting techniques, and selected tissues by the researchers, it is very important to examine the existing literature. To find trends in 3D bioprinting research, this work conducted an systematic literature review of 3D bioprinting.
    UNASSIGNED: This literature provides a thorough study and analysis of research articles on bioprinting from 2000 to 2022 that were extracted from the Scopus database. The articles selected for analysis were classified according to the year of publication, articles and publishers, nation, authors who are working in bioprinting area, universities, biomaterial used, and targeted applications.
    UNASSIGNED: The top nations, universities, journals, publishers, and writers in this field were picked out after analyzing research publications on bioprinting. During this study, the research themes and research trends were also identified. Furthermore, it has been observed that there is a need for additional research in this domain for the development of bioink and their properties that can guide practitioners and researchers while selecting appropriate combinations of biomaterials to obtain bioink suitable for mimicking human tissue.
    UNASSIGNED: This research includes research findings, recommendations, and observations for bioprinting researchers and practitioners. This article lists significant research gaps, future research directions, and potential application areas for bioprinting.
    UNASSIGNED: The review conducted here is mainly focused on the process of collecting, organizing, capturing, evaluating, and analyzing data to give a deeper understanding of bioprinting and to identify potential future research trends.
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  • 文章类型: Journal Article
    多层皮肤结构包括表皮,真皮和皮下组织,形成由细胞外基质(ECM)组成的复杂组织。当皮肤受伤时,伤口修复是一个精心策划的过程。然而,这种自然的伤口修复对于大面积的伤口是无效的。基于自体移植的治疗是有效的,但是,患者的额外疼痛和二次愈合限制了其成功应用。因此,对于制造组织工程化皮肤构建体存在相当大的需求。成功的皮肤移植的发展需要对天然皮肤及其愈合过程有基本的了解,以及选择生物聚合物和适当制造技术的设计标准。Further,制造合适的皮肤移植物需要满足物理化学,机械,和相当于天然皮肤的生物特性。先进的3D生物打印提供了功能组件放置的空间控制,例如具有活细胞的生物聚合物,可以满足准备理想的皮肤移植物的先决条件。在这个观点中,这里我们详细阐述了基本的设计要求,皮肤移植物的制造和墨水的选择所涉及的限制,3D生物打印技术可能的解决方案,以及他们的最新进展,挑战,和前景。
    The multi-layered skin structure includes the epidermis, dermis and hypodermis, which forms a sophisticated tissue composed of extracellular matrix (ECM). The wound repair is a well-orchestrated process when the skin is injured. However, this natural wound repair will be ineffective for large surface area wounds. Autografts-based treatment is efficient but, additional pain and secondary healing of the patient limits its successful application. Therefore, there is a substantial need for fabricating tissue-engineered skin constructs. The development of a successful skin graft requires a fundamental understanding of the natural skin and its healing process, as well as design criteria for selecting a biopolymer and an appropriate fabrication technique. Further, the fabrication of an appropriate skin graft needs to meet physicochemical, mechanical, and biological properties equivalent to the natural skin. Advanced 3D bioprinting provides spatial control of the placement of functional components, such as biopolymers with living cells, which can satisfy the prerequisites for the preparation of an ideal skin graft. In this view, here we elaborate on the basic design requirements, constraints involved in the fabrication of skin graft and choice of ink, the probable solution by 3D bioprinting technique, as well as their latest advancements, challenges, and prospects.
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  • 文章类型: Journal Article
    医学中生物组织的再生具有挑战性,3D生物打印提供了一种创新的方式来创建功能多细胞组织。生物打印的一种常见方式是生物墨水,这是一种负载细胞的水凝胶。对于临床应用,然而,生物打印仍然表现令人满意,例如,在血管化方面,有效的抗菌,免疫调节,和胶原蛋白沉积的调节。许多研究将不同的生物活性材料结合到3D打印支架中,以优化生物打印。这里,我们回顾了添加到3D生物打印水凝胶中的各种添加剂。生物再生的基本机制和方法是重要的,并将为未来的研究提供有用的基础。
    The regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink, which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g., in vascularization, effective antibacterial, immunomodulation, and regulation of collagen deposition. Many studies incorporated different bioactive materials into the 3D-printed scaffolds to optimize the bioprinting. Here, we reviewed a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide a useful basis for future research.
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  • 文章类型: Journal Article
    兼容的肝脏供体的绝对短缺和潜在接受者的数量不断增加,导致科学家们探索从生物工程来源提供组织/器官替代品的替代方法。完整功能的组织/器官置换的生物人工再生高度依赖于工程工具的正确组合,生物学原理,和物质生物学视野。在过去的二十年里,通过融合各种先进的跨学科研究方法,在肝组织工程方面取得了令人瞩目的成就。三维(3D)生物打印已成为一种有前途的最先进的工具,具有使用由含水微环境组成的粘度和降解控制的可打印生物墨水制造体积肝脏组织/器官等效物的强大潜力,和含有活细胞和相关补充剂的制剂。来源,生化,或热机械性能和交联反应动力学是理想的生物墨水配方和实现生物打印过程的先决条件。在这次审查中,我们深入研究了生物打印技术的潜在未来效用的预测,以及组织/器官特异性脱细胞生物材料作为生物墨水底物的前景。之后,我们概述了去细胞化的各种方法,以及最相关的研究将脱细胞生物墨水应用于体外肝脏模型的生物工程。最后,提出了基于脱细胞材料的生物打印在临床再生医学方向上的挑战和未来前景,以促进进一步的发展。
    The absolute shortage of compatible liver donors and the growing number of potential recipients have led scientists to explore alternative approaches to providing tissue/ organ substitutes from bioengineered sources. Bioartificial regeneration of a fully functional tissue/organ replacement is highly dependent on the right combination of engineering tools, biological principles, and materiobiology horizons. Over the past two decades, remarkable achievements have been made in hepatic tissue engineering by converging various advanced interdisciplinary research approaches. Three-dimensional (3D) bioprinting has arisen as a promising state-of-the-art tool with strong potential to fabricate volumetric liver tissue/organ equivalents using viscosity- and degradation-controlled printable bioinks composed of hydrous microenvironments, and formulations containing living cells and associated supplements. Source of origin, biophysiochemical, or thermomechanical properties and crosslinking reaction kinetics are prerequisites for ideal bioink formulation and realizing the bioprinting process. In this review, we delve into the forecast of the potential future utility of bioprinting technology and the promise of tissue/organ- specific decellularized biomaterials as bioink substrates. Afterward, we outline various methods of decellularization, and the most relevant studies applying decellularized bioinks toward the bioengineering of in vitro liver models. Finally, the challenges and future prospects of decellularized material-based bioprinting in the direction of clinical regenerative medicine are presented to motivate further developments.
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