This article is part of the Polymeric Biomaterials special issue. In the last 18 months, a global health crisis due to the rise, spread, and epidemiology of SARS (CoV-2) COVID19 has ravaged all of mankind. Fortunately, fundamental advances in materials, molecular biology, bioengineering, and advanced manufacturing have provided the understanding and ability to identify the pathogen, characterize the protein coat structure, and formulate a new mRNA vaccine and delivery strategy that has likely changed global health forever. Although currently focused primarily on the single target of COVID19, this technology will lead to foundational changes in the approach of researchers in their ongoing efforts to develop therapeutics against AIDS, cancer, and numerous other diseases. Key to the success of the COVID19 vaccine strategy was a material approach to package, stabilize, traffic, and deliver mRNA, which in very short order transitioned from discovery to laboratory curiosity to clinical trials and ultimate regulatory approval and use. Many contributed to this effort over several preceding decades of basic and applied research, with the development of a “new” delivery system providing a critical role in vaccine efficacy. Without this materials innovation, the mRNA vaccines would likely not have succeeded, as existing and widely utilized polymeric formulations and delivery strategies are not compatible with mRNA. Such advances in the development and understanding of biomaterials across widespread applications is the focus of this thematic issue on Polymeric Biomaterials. The past decades have seen extensive growth in our understanding and development of new polymeric biomaterials for various biomedical applications, including in the development of new therapies and biological understanding. Commonly thought to act as inert structural materials that may be degradable, polymeric biomaterials have evolved to induce specific biological responses, act dynamically based on extrinsic signals, traffic through cellular membranes, and be processed using widespread techniques such as with biofabrication tools. Advances in synthetic technologies, as well as materials processing, have opened up material properties and structures that were previously unattainable. These systems are being explored as in vitro platforms for cell culture to uncover new biology, as tissue models to rapidly screen pharmaceutics, or for the development of commercially viable and translationally relevant therapies in applications from tissue adhesives to gene therapy. The use of biomaterials and particularly degradable polymers in medical applications is not a new concept. First reported in the use of resorbable sutures in 1974, poly(lactic acid) (PLA) and subsequently poly(glycolic acid) (PGA), poly(caprolactone) (PCL), and their respective copolymers such as poly(lactic-co-glycolic acid) (PLGA) have been used in applications ranging from solid implantable devices ranging from resorbable bone screws to injectable devices for drug elution. Despite known limitations, over the past 30 years or more, this small library of degradable polymeric materials has dominated the market in products that have gained regulatory approval for commercial use in humans. Considering the advances in polymer science, it is surprising that the diversity of biodegradable materials approved for clinical use is not greater. From a chemical perspective, the design space is limited only by creativity, time, and resources, and hence, surely there are materials better suited to in vivo applications that remain to be discovered or translated to clinical use. While the PLGA family has found, and will continue to find, much success, especially in the area of drug delivery, this focus on the use of these existing and available polyester materials for an ever-increasing range of applications is inherently limiting. In many cases the materials have mechanical and physical properties that do not adequately fit those of the tissues that they are being designed to treat, which from a materials perspective, makes it feel like trying to fit a square peg in a round hole. Thus, the continuing need for a better understanding of biomaterials, as well as their innovation, is clear. This thematic review on Polymeric Biomaterials contains a range of reviews on important topics in this field that we hope will challenge the reader to understand the past and look toward how materials are evolving to meet new biomedical needs. Specifically, we have broken the reviews into three topical areas: (1) Classes of synthetic and naturally derived polymeric biomaterials, (2) advanced methods for the fabrication and characterization of polymeric biomaterials, and (3) applications of polymeric biomaterials. New classes of synthetic and naturally derived materials are needed to advance biomedicine to expand on the available properties of biomaterials (topical area 1). Cooper-White and co-workers provide a comprehensive review on the emergence of high throughput technologies to rapidly synthesize and characterize new biomaterials. These technologies are accelerating the discovery of new biomaterials at previously unimaginable rates, using methods such as automated liquid handling, robotics, and microfluidics. The rapid screening of such biomaterials with cells and tissues and the advancement of tools in the design of experiments, machine learning, and bioinformatics are equally important to advance the field. Focusing on one specific class of biomaterials that has emerged with important properties of biocompatibility and controlled degradation, Dove and co-workers provide an overview of the development of aliphatic polycarbonates. There is great chemical diversity to this class of polymers based on synthetic reagents, resulting in widespread degradation behaviors through hydrolysis, enzymatic breakdown, oxidation, and stimuli-responsive means. Aliphatic polycarbonates have been widely explored for drug and gene therapy, imaging, and scaffolds for tissue repair. Beyond purely synthetic materials, there is great interest in the use of naturally derived polymers in the fabrication of biomaterials, exploiting inherent biofunctionality, such as cell adhesion and degradation. Muir and Burdick provide a detailed review of the range of chemical modifications to biopolymers, including polysaccharides and polypeptides, for the formation of biomedical hydrogels. These chemical modifications allow the linking of biopolymers together and control over hydrogel properties through physical and covalent cross-links for applications as scaffolds fabricated through biofabrication techniques, the delivery of therapeutics, and tissue adhesives. Chen and co-workers then expand on this general class of materials, with a focus on carbohydrates that are found abundantly in the extracellular matrix of animals and the cell walls of plants and bacteria. These include molecules such as polysaccharides, glycopolymers, and glycoproteins and give function to formed biomaterials for widespread application in drug delivery, tissue engineering, and immunology. Weil and co-workers then review the use of DNA in combination with polymers to form functional materials, through techniques such as DNA templating and the fabrication of nanoscale structures with precise designs. DNA offers unique customization at small length scales that is challenging with alternate approaches. Beyond their synthesis, it is important to understand various fabrication techniques to process biomaterials into usable materials, as well as techniques to characterize biomaterial properties (topical area 2). As one approach, cells are often embedded in hydrogels for use as tissue models or for therapeutics and biomaterials provide a range of signals to drive cell behaviors. Bryant and co-workers review both experimental and computational approaches that are being used to understand the fundamentals of hydrogels in these applications, such as their mechanical properties and the resulting cellular behaviors such as mechanosensing, migration, growth, tissue deposition, and matrix elaboration. The review includes a comprehensive overview of published literature, as well as guidance on the integration of experiments and models in these applications. Continuing in the area of hydrogels, Bian and co-workers review the growing area of dynamic hydrogels where properties change over time, such as through biomaterial degradation (e.g., hydrolysis, light-mediated) or through physical interactions between polymers (e.g., ionic bonding, coordination bonds). They further review the applications of dynamic hydrogels, such as in exploring the dynamics of cellular microenvironments in development and disease, fabricating viscoelastic materials to mimic tissue properties, culturing organoids in 3D environments, and for controlled drug delivery. Toward porous biomaterials development, Groll and co-workers provide an overview of the fabrication of electrospun fibrous biomaterials, which exhibit high surface area, high porosity, and structures similar to the natural extracellular matrix. They cover topics related to the verstatile chemistry that has been implemented into electrospun scaffolds, including through the modification of fibers to impart biological functionality into the materials. Further, the review provides extensive information on the various tools that are being used to characterize the functionality of electrospun scaffolds. Becker and co-workers then provide a comprehensive review on various techniques that are used to fabricate scaffolds out of biodegradable materials for widespread applications including tissue engineering, drug delivery, wound healing, and implantable medical devices. A wide range of techniques have emerged, including additive manufacturing (e.g., vat photopolymerization, powder bed fusion), fiber-based scaffold fabrication (e.g., electrospinning), and conventional polymer processing (e.g., molding, poragen leaching). The review further expands on stimuli-responsive materials and the various sterilization approaches that are needed for implantable materials. As a last review in this topical area, Spiller and co-workers cover approaches to characterize and understand inflammatory responses to polymeric biomaterials. This is of course a very important area, to both understand polymeric biomaterials in their intended applications and to also control and improve these interactions with new materials through controlled chemistry and released immunomodulators to promote optimal integration. There are many challenges in this field and a range of new tools and understanding on the horizon to improve biomaterials for therapeutic use. The success of polymeric biomaterials is dependent on controlled inflammatory responses in vivo. Although the prior reviews also mention biomaterials applications, the last set of reviews are focused on specific application areas and how polymeric biomaterials have been designed to meet the needs of biomedicine (topical area 3). To begin, Nam and Mooney review the wide array of polymeric tissue adhesives that have been developed in the past decades for wound healing applications, including wound closure, hemostats, and to promote tissue healing. Such materials have been designed from synthetic polymers, natural polymers, and with inspiration from nature (e.g., mussels, geckos). They end with a discussion of next generation adhesive biomaterials that have added functionality and improved properties. Appel and co-workers provide a review on the translation of hydrogel biomaterials across applications in drug delivery, cell therapies, and surgical applications and include various design criteria for this class of materials with an emphasis on mechanical and rheological properties. Further, they review those injectable hydrogels that have translated to the clinic and provide thoughts on manufacturing steps toward this. Ma and co-workers then describe the emergence of hydrogels in the specific treatment of type 1 diabetes. Hydrogels have been designed for the release of insulin, including with glucose-responsive and pH-sensitive designs and through delivery as patches, injectables, or oral administration. Further, hydrogels have been used for the encapsulation and delivery of insulin-secreting cells to deliver and protect them from the host response. More specific to drug delivery, polymeric biomaterials have made great progress in the delivery of genes and peptides, to overcome limitations in translation and efficacy of prior techniques. Reineke and co-workers review the diverse polymers that have been used in the delivery of nucleic acids, including design features such as polymer structure, molecular weight, charge, and hydrophobicity. They further review the various chemistries used in the formation of engineered multifunctional polyplexes and the challenges in implementing them for cellular transfection. Lastly, Pun and co-workers review the development and design of polymeric carriers to improve intracellular peptide delivery specifically for cancer treatments. Appropriately designed carriers can increase accumulation and uptake of peptides and aid in the targeting of specific organelles for therapy. In summary, there have been many great advances in polymeric biomaterials in recent years that will likely have great impact on fundamental knowledge and patient treatment, such as those now being used to treat COVID-19. As these reviews show, the synthesis, processing, and application of biomaterials involve a wide range of specific polymer chemistries and properties that are likely to make further advances in the future. It is exciting to consider what the future may bring in the area of polymeric biomaterials. Matthew L. Becker is the Hugo L. Blomquist Distinguished Professor at Duke University. His research team is focused on developing novel molecular building blocks, degradable polymeric materials, and additive manufacturing methods for addressing unmet needs at the intersection of chemistry, materials, and medicine. He received a Ph.D. in Organic Chemistry from Washington University in St. Louis and was an NRC Postdoctoral Fellow and then staff member in the Polymers Division at NIST. From 2009–2019, he was the W. Gerald Austen Endowed Chair in Polymer Science and Engineering at the University of Akron. He is a Fellow of the American Chemical Society, the American Institute of Medical and Biomedical Engineering, and the Royal Society of Chemistry. Jason A. Burdick received his Ph.D. in Chemical Engineering from the University of Colorado Boulder and then completed a postdoctoral fellowship at Massachusetts Institute of Technology. He moved to the Department of Bioengineering at the University of Pennsylvania in 2005 where he is now the Robert D. Bent Professor. His expertise is in the development of hydrogel biomaterials and elastomers, their processing through techniques such as electrospinning and 3D bioprinting, and their application in mechanobiology and musculoskeletal and cardiovascular tissue repair. He has also founded several companies for the translation of technology from his laboratory and has been recognized as a fellow of the American Institute for Medical and Biological Engineering, the National Academy of Inventors, the International College of Fellows of Biomaterials Science and Engineering, and the Biomedical Engineering Society. This article has not yet been cited by other publications.

中文翻译：

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简介：高分子生物材料

本文是部分高分子生物材料特刊。在过去的 18 个月中，由于 SARS (CoV-2) COVID19 的上升、传播和流行病学导致的全球健康危机席卷了全人类。幸运的是，材料、分子生物学、生物工程和先进制造方面的基本进步提供了识别病原体、表征蛋白质外壳结构以及制定可能永远改变全球健康的新 mRNA 疫苗和递送策略的理解和能力。尽管目前主要关注 COVID19 的单一目标，但这项技术将导致研究人员在开发针对艾滋病、癌症和许多其他疾病的治疗方法的持续努力中的方法发生根本性变化。COVID19 疫苗策略成功的关键是包装、稳定、运输和传递 mRNA 的材料方法，它在很短的时间内从发现转变为实验室好奇心，再到临床试验和最终的监管批准和使用。许多人在过去几十年的基础和应用研究中为这项工作做出了贡献，开发了一种“新”递送系统，在疫苗效力方面发挥了关键作用。如果没有这种材料创新，mRNA 疫苗可能不会成功，因为现有和广泛使用的聚合物配方和递送策略与 mRNA 不兼容。在广泛应用的生物材料的开发和理解方面取得的这些进展是本专题关于聚合物生物材料的重点。在过去的几十年中，我们对用于各种生物医学应用的新型聚合物生物材料的理解和开发有了广泛的增长，包括开发新疗法和生物学理解。通常认为作为可降解的惰性结构材料，聚合生物材料已经进化为诱导特定的生物反应，根据外在信号动态发挥作用，通过细胞膜进行运输，并使用广泛的技术（如生物制造工具）进行加工。合成技术以及材料加工的进步开辟了以前无法实现的材料特性和结构。这些系统正在被探索为 通过细胞膜运输，并使用广泛的技术进行处理，例如使用生物制造工具。合成技术以及材料加工的进步开辟了以前无法实现的材料特性和结构。这些系统正在被探索为 通过细胞膜运输，并使用广泛的技术进行处理，例如使用生物制造工具。合成技术以及材料加工的进步开辟了以前无法实现的材料特性和结构。这些系统正在被探索为用于细胞培养以发现新生物学的体外平台，作为快速筛选药物的组织模型，或用于开发从组织粘合剂到基因治疗的应用中具有商业可行性和转化相关的疗法。在医疗应用中使用生物材料，尤其是可降解聚合物并不是一个新概念。1974 年首次报道使用可吸收缝线，聚乳酸（PLA）和随后的聚乙醇酸（PGA）、聚己内酯（PCL）以及它们各自的共聚物，如聚乳酸-乙醇酸) (PLGA) 已用于各种应用，从可吸收骨螺钉到用于药物洗脱的可注射装置的固体植入装置。尽管存在已知的局限性，但在过去 30 年或更长时间中，这个小型可降解聚合物材料库在已获得监管部门批准可用于人类商业用途的产品市场中占据主导地位。考虑到聚合物科学的进步，令人惊讶的是，批准用于临床的可生物降解材料的多样性并不多。从化学的角度来看，设计空间只受创造力、时间和资源的限制，因此，肯定有更适合体内的材料仍有待发现或转化为临床应用的应用。虽然 PLGA 家族已经取得并将继续取得巨大成功，特别是在药物输送领域，但将这些现有和可用的聚酯材料用于不断扩大的应用范围的做法本身就受到限制。在许多情况下，这些材料的机械和物理特性不能充分适应它们被设计用于治疗的组织，从材料的角度来看，这让人感觉像是试图将一个方形钉子安装在一个圆孔中。因此，对更好地理解生物材料及其创新的持续需求是显而易见的。这篇关于聚合物生物材料的专题评论包含对该领域重要主题的一系列评论，我们希望这些评论将挑战读者了解过去，并了解材料如何发展以满足新的生物医学需求。具体来说，我们将评论分为三个主题领域：（1）合成和天然衍生的聚合物生物材料的类别，（2）聚合物生物材料的制造和表征的先进方法，以及（3）聚合物生物材料的应用。需要新类别的合成和天然衍生材料来推进生物医学，以扩展生物材料的可用特性（(1) 合成和天然衍生的聚合物生物材料类别，(2) 聚合物生物材料的制造和表征的先进方法，以及 (3) 聚合物生物材料的应用。需要新类别的合成和天然衍生材料来推进生物医学，以扩展生物材料的可用特性（(1) 合成和天然衍生的聚合物生物材料类别，(2) 聚合物生物材料的制造和表征的先进方法，以及 (3) 聚合物生物材料的应用。需要新类别的合成和天然衍生材料来推进生物医学，以扩展生物材料的可用特性（主题领域 1）。Cooper-White 及其同事对快速合成和表征新生物材料的高通量技术的出现进行了全面审查。这些技术使用自动化液体处理、机器人技术和微流体等方法，正在以前所未有的速度加速新生物材料的发现。用细胞和组织快速筛选此类生物材料，以及在实验、机器学习和生物信息学设计中改进工具对于推进该领域同样重要。Dove 及其同事专注于一类具有生物相容性和可控降解的重要特性的特定生物材料，概述了脂肪族聚碳酸酯的发展。这类基于合成试剂的聚合物具有很大的化学多样性，通过水解、酶分解、氧化和刺激响应手段导致广泛的降解行为。脂肪族聚碳酸酯已被广泛用于药物和基因治疗、成像和组织修复支架。除了纯合成材料之外，人们对在生物材料的制造中使用天然衍生的聚合物、利用固有的生物功能（例如细胞粘附和降解）产生了浓厚的兴趣。Muir 和 Burdick 详细回顾了对生物聚合物（包括多糖和多肽）进行化学修饰的范围，以形成生物医学水凝胶。这些化学修饰允许将生物聚合物连接在一起，并通过物理和共价交联控制水凝胶特性，用于通过生物制造技术制造的支架、治疗剂的传递和组织粘合剂。Chen 和他的同事随后扩展了这一类材料，重点关注在动物细胞外基质以及植物和细菌细胞壁中大量发现的碳水化合物。这些包括多糖、糖聚合物和糖蛋白等分子，并赋予形成的生物材料功能，以广泛应用于药物递送、组织工程和免疫学。Weil 及其同事随后回顾了 DNA 与聚合物结合使用以形成功能材料，通过诸如 DNA 模板和制造具有精确设计的纳米级结构等技术。DNA 在小长度尺度上提供独特的定制，这对替代方法具有挑战性。除了它们的合成之外，了解将生物材料加工成可用材料的各种制造技术以及表征生物材料特性的技术也很重要。主题领域 2）。作为一种方法，细胞通常嵌入水凝胶中，用作组织模型或用于治疗，生物材料提供一系列信号来驱动细胞行为。Bryant 及其同事回顾了用于了解水凝胶在这些应用中的基本原理的实验和计算方法，例如它们的机械性能和由此产生的细胞行为，例如机械传感、迁移、生长、组织沉积和基质加工。该评论包括对已发表文献的全面概述，以及在这些应用程序中整合实验和模型的指导。继续研究水凝胶领域，Bian 和他的同事回顾了动态水凝胶不断增长的领域，其中特性随时间而变化，例如通过生物材料降解（例如水解、光介导）或通过聚合物之间的物理相互作用（例如，离子键、配位键）。他们进一步回顾了动态水凝胶的应用，例如探索细胞微环境在发育和疾病中的动力学、制造粘弹性材料以模拟组织特性、在 3D 环境中培养类器官以及控制药物输送。对于多孔生物材料的开发，Groll 及其同事概述了电纺纤维生物材料的制造，这些材料具有高表面积、高孔隙率和类似于天然细胞外基质的结构。它们涵盖了与已在静电纺丝支架中实施的多功能化学相关的主题，包括通过对纤维进行改性以将生物功能赋予材料。进一步，该审查提供了有关用于表征电纺支架功能的各种工具的广泛信息。然后，Becker 和他的同事对用于使用可生物降解材料制造支架的各种技术进行了全面审查，这些技术用于广泛的应用，包括组织工程、药物输送、伤口愈合和可植入医疗设备。已经出现了广泛的技术，包括增材制造（例如，大桶光聚合、粉末床融合）、基于纤维的支架制造（例如，静电纺丝）和传统的聚合物加工（例如，模塑、poragen 浸出）。该审查进一步扩展了刺激响应材料和可植入材料所需的各种灭菌方法。作为该主题领域的最后一篇综述，Spiller 及其同事介绍了表征和理解对聚合生物材料的炎症反应的方法。这当然是一个非常重要的领域，既要了解聚合物生物材料在其预期应用中的用途，又要通过受控化学和释放的免疫调节剂来控制和改善这些与新材料的相互作用，以促进最佳整合。该领域存在许多挑战，并且即将出现一系列新工具和新认识，以改进用于治疗用途的生物材料。聚合物生物材料的成功取决于受控的炎症反应 既要了解聚合物生物材料在其预期应用中的用途，又要通过受控化学和释放的免疫调节剂来控制和改善这些与新材料的相互作用，以促进最佳整合。该领域存在许多挑战，并且即将出现一系列新工具和新认识，以改进用于治疗用途的生物材料。聚合物生物材料的成功取决于受控的炎症反应 既要了解聚合物生物材料在其预期应用中的用途，又要通过受控化学和释放的免疫调节剂来控制和改善这些与新材料的相互作用，以促进最佳整合。该领域存在许多挑战，并且即将出现一系列新工具和新认识，以改进用于治疗用途的生物材料。聚合物生物材料的成功取决于受控的炎症反应在体内。虽然之前的评论也提到了生物材料的应用，但最后一组评论集中在特定的应用领域以及如何设计聚合物生物材料以满足生物医学的需求（主题领域 3）。首先，Nam 和 Mooney 回顾了过去几十年为伤口愈合应用开发的各种聚合物组织粘合剂，包括伤口闭合、止血剂和促进组织愈合。此类材料是由合成聚合物、天然聚合物设计的，灵感来自大自然（例如贻贝、壁虎）。他们最后讨论了具有附加功能和改进性能的下一代粘合剂生物材料。Appel 及其同事回顾了水凝胶生物材料在药物输送、细胞疗法和外科应用中的应用，包括此类材料的各种设计标准，重点是机械和流变特性。进一步，他们审查了那些已转化为临床的可注射水凝胶，并提供了有关制造步骤的想法。Ma 及其同事随后描述了水凝胶在 1 型糖尿病的特定治疗中的出现。水凝胶被设计用于释放胰岛素，包括葡萄糖响应和 pH 敏感设计，以及通过贴剂、注射剂或口服给药的方式给药。此外，水凝胶已被用于封装和递送胰岛素分泌细胞，以递送和保护它们免受宿主反应。更具体地用于药物递送，聚合物生物材料在基因和肽的递送方面取得了很大进展，以克服现有技术在翻译和功效方面的限制。Reineke 及其同事回顾了用于核酸递送的多种聚合物，包括聚合物结构、分子量、电荷和疏水性等设计特征。他们进一步回顾了用于形成工程化多功能复合物的各种化学物质以及将它们用于细胞转染的挑战。最后，Pun 和同事审查了聚合物载体的开发和设计，以改善专门用于癌症治疗的细胞内肽递送。适当设计的载体可以增加肽的积累和摄取，并有助于靶向特定细胞器进行治疗。总之，近年来高分子生物材料取得了许多重大进展，可能会对基础知识和患者治疗产生重大影响，例如现在用于治疗 COVID-19 的药物。正如这些评论所示，生物材料的合成、加工和应用涉及广泛的特定聚合物化学和特性，这些特性可能会在未来取得进一步的进展。考虑未来可能会在聚合物生物材料领域带来什么是令人兴奋的。Matthew L. Becker 是杜克大学的 Hugo L. Blomquist 特聘教授。他的研究团队专注于开发新型分子构件、可降解聚合物材料和增材制造方法，以解决化学、材料和医学交叉领域未满足的需求。他获得了博士学位。在圣路易斯华盛顿大学获得有机化学博士学位，曾是 NRC 博士后研究员，然后是 NIST 聚合物部门的工作人员。从 2009 年到 2019 年，他是阿克伦大学聚合物科学与工程的 W. Gerald Austen 基金会主席。他是美国化学学会、美国医学与生物医学工程研究所和皇家化学学会的会员。Jason A. Burdick 获得了博士学位。在科罗拉多大学博尔德分校获得化学工程博士学位，然后在麻省理工学院完成了博士后研究。2005 年，他搬到宾夕法尼亚大学的生物工程系，现在是罗伯特 D. 本特教授。他的专长是水凝胶生物材料和弹性体的开发，通过静电纺丝和 3D 生物打印等技术进行加工，以及它们在机械生物学和肌肉骨骼和心血管组织修复中的应用。他还创立了多家公司，将其实验室的技术转化为美国医学和生物工程研究所、美国国家发明家学院、国际生物材料科学与工程学院研究员和生物医学工程学会。这篇文章尚未被其他出版物引用。