Microfluidic Platforms toward Rational Material Fabrication for Biomedical Applications

The emergence of micro/nanomaterials in recent decades has brought promising alternative approaches in various biomedicine‐related fields such as pharmaceutics, diagnostics, and therapeutics. These micro/nanomaterials for specific biomedical applications shall possess tailored properties and functionalities that are closely correlated to their geometries, structures, and compositions, therefore placing extremely high demands for manufacturing techniques. Owing to the superior capabilities in manipulating fluids and droplets at microscale, microfluidics has offered robust and versatile platform technologies enabling rational design and fabrication of micro/nanomaterials with precisely controlled geometries, structures and compositions in high throughput manners, making them excellent candidates for a variety of biomedical applications. This review briefly summarizes the progress of microfluidics in the fabrication of various micro/nanomaterials ranging from 0D (particles), 1D (fibers) to 2D/3D (film and bulk materials) materials with controllable geometries, structures, and compositions. The applications of these microfluidic‐based materials in the fields of diagnostics, drug delivery, organs‐on‐chips, tissue engineering, and stimuli‐responsive biodevices are introduced. Finally, an outlook is discussed on the future direction of microfluidic platforms for generating materials with superior properties and on‐demand functionalities. The integration of new materials and techniques with microfluidics will pave new avenues for preparing advanced micro/nanomaterials with enhanced performance for biomedical applications.     

Piezoelectric Biomaterials for Sensors and Actuators

Recent advances in materials, manufacturing, biotechnology, and microelectromechanical systems (MEMS) have fostered many exciting biosensors and bioactuators that are based on biocompatible piezoelectric materials. These biodevices can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. Herein, the principles, applications, future opportunities, and challenges of piezoelectric biomaterials for medical uses are reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed with new materials and advanced methods in microfabrication/encapsulation to avoid the toxicity of conventional lead‐based piezoelectric materials. Intriguingly, some piezoelectric materials are biodegradable in nature, which eliminates the need for invasive implant extraction. Together, these advancements in the field of piezoelectric materials and microsystems can spark a new age in the field of medicine.     

Integrated Micro/Nanoengineered Functional Biomaterials for Cell Mechanics and Mechanobiology: A Materials Perspective

The rapid development of micro/nanoengineered functional biomaterials in the last two decades has empowered materials scientists and bioengineers to precisely control different aspects of the in vitro cell microenvironment. Following a philosophy of reductionism, many studies using synthetic functional biomaterials have revealed instructive roles of individual extracellular biophysical and biochemical cues in regulating cellular behaviors. Development of integrated micro/nanoengineered functional biomaterials to study complex and emergent biological phenomena has also thrived rapidly in recent years, revealing adaptive and integrated cellular behaviors closely relevant to human physiological and pathological conditions. Working at the interface between materials science and engineering, biology, and medicine, we are now at the beginning of a great exploration using micro/nanoengineered functional biomaterials for both fundamental biology study and clinical and biomedical applications such as regenerative medicine and drug screening. In this review, an overview of state of the art micro/nanoengineered functional biomaterials that can control precisely individual aspects of cell‐microenvironment interactions is presented and they are highlighted them as well‐controlled platforms for mechanistic studies of mechano‐sensitive and ‐responsive cellular behaviors and integrative biology research. The recent exciting trend where micro/nanoengineered biomaterials are integrated into miniaturized biological and biomimetic systems for dynamic multiparametric microenvironmental control of emergent and integrated cellular behaviors is also discussed. The impact of integrated micro/nanoengineered functional biomaterials for future in vitro studies of regenerative medicine, cell biology, as well as human development and disease models are discussed.     

The influence of plasma technology coupled to chemical grafting on the cell growth compliance of 3D hydroxyapatite scaffolds

The development of advanced materials with biomimetic features in order to elicit desired biological responses and to guarantee tissue biocompatibility is recently gaining attention for tissue engineering applications. Bioceramics, such as hydroxyapatite-based biomaterials are now used in a number of different applications throughout the body, covering all areas of the skeleton, due to their biological and chemical similarity to the inorganic phases of bones. When bioactive sintered hydroxyapatite (HA) is desired, biomolecular modification of these materials is needed. In the present work, we investigated the influence of plasma surface modification coupled to chemical grafting on the cell growth compliance of HA 3D scaffolds.     

Liquid Metal–Based Soft Microfluidics

Motivated by the increasing demand of wearable and soft electronics, liquid metal (LM)‐based microfluidics has been subjected to tremendous development in the past decade, especially in electronics, robotics, and related fields, due to the unique advantages of LMs that combines the conductivity and deformability all‐in‐one. LMs can be integrated as the core component into microfluidic systems in the form of either droplets/marbles or composites embedded by polymer materials with isotropic and anisotropic distribution. The LM microfluidic systems are found to have broad applications in deformable antennas, soft diodes, biomedical sensing chips, transient circuits, mechanically adaptive materials, etc. Herein, the recent progress in the development of LM‐based microfluidics and their potential applications are summarized. The current challenges toward industrial applications and future research orientation of this field are also summarized and discussed.     

生物体用金属材料及表面处理

综述了生物体用金属材料的发展、性能及应用 ,并重点论述了最新表面处理技术在生物体用金属材料表面上的应用 ,用以制备表面性能优异的仿生生物材料。     

Microfluidics for Production of Particles: Mechanism,Methodology, and Applications

In the past two decades, microfluidics‐based particle production is widely applied for multiple biological usages. Compared to conventional bulk methods, microfluidic‐assisted particle production shows significant advantages, such as narrower particle size distribution, higher reproducibility, improved encapsulation efficiency, and enhanced scaling‐up potency. Herein, an overview of the recent progress of the microfluidics technology for nano‐, microparticles or droplet fabrication, and their biological applications is provided. For both nano‐, microparticles/droplets, the previously established mechanisms behind particle production via microfluidics and some typical examples during the past five years are discussed. The emerging interdisciplinary technologies based on microfluidics that have produced microparticles or droplets for cellular analysis and artificial cells fabrication are summarized. The potential drawbacks and future perspectives are also briefly discussed.     

镁基生物涂层材料研究现状

镁及镁合金作为硬组织植入替代材料具有显著的优越性,但如何对镁及镁合金进行表面改性以满足临床应用对生物材料耐蚀性能的苛刻要求,仍然是解决镁及镁合金在生物材料领域产业化应用的关键。本文综述了为提高镁基生物材料耐蚀性能研发的涂层材料种类、涂层表面改性技术的研究现状,提出了结合多种制备方法,通过对涂层的组成和结构设计来改善涂层的结合强度、稳定性及良好的生物适应性是今后努力的方向。     

Continuous-flow lithography for high-throughput microparticle synthesis

Precisely shaped polymeric particles and structures are widely used for applications in photonic materials, MEMS, biomaterials and self-assembly. Current approaches for particle synthesis are either batch processes or flow-through microfluidic schemes that are based on two-phase systems, limiting the throughput, shape and functionality of the particles. We report a one-phase method that combines the advantages of microscope projection photolithography and microfluidics to continuously form morphologically complex or multifunctional particles down to the colloidal length scale. Exploiting the inhibition of free-radical polymerization near PDMS surfaces, we are able to repeatedly pattern and flow rows of particles in less than 0.1 s, affording a throughput of near 100 particles per second using the simplest of device designs. Polymerization was also carried out across laminar, co-flowing streams to generate Janus particles containing different chemistries, whose relative proportions could be easily tuned. This new high-throughput technique offers unprecedented control over particle size, shape and anisotropy.     

Responsive biomaterials for 3D bioprinting: A review

Three-dimensional (3D) bioprinting enables a controlled deposition of cells, biomaterials, and biological compounds (i.e., bioinks) to build complex 3D biological models, biological living systems, and therapeutic products. Developing responsive biomaterials as novel bioinks has been a central focus of research in the field of bioprinting because of their controllable material properties in response to printing-induced external or internal stimuli. In this review, we highlight the most recent advances of responsive biomaterials for 3D bioprinting applications. We review commonly used stimuli-responsive biomaterials and strategies for utilizing multifunctional responsiveness to achieve desirable printability, structural formability, cell viability, and construct bioactivity for 3D bioprinting. We also summarize major bioink formulation strategies currently adopted in 3D bioprinting. We subsequently discuss several promising applications of 3D printing involving responsive biomaterials, such as bioprinting in a supporting bath, 4D bioprinting, and bioprinting new controlled drug delivery systems. Future perspectives on the design and development of novel multifunctional bioinks based on responsive biomaterials and technological innovations are also presented.     

Advances in Biomaterials for Drug Delivery

Advances in biomaterials for drug delivery are enabling significant progress in biology and medicine. Multidisciplinary collaborations between physical scientists, engineers, biologists, and clinicians generate innovative strategies and materials to treat a range of diseases. Specifically, recent advances include major breakthroughs in materials for cancer immunotherapy, autoimmune diseases, and genome editing. Here, strategies for the design and implementation of biomaterials for drug delivery are reviewed. A brief history of the biomaterials field is first established, and then commentary on RNA delivery, responsive materials development, and immunomodulation are provided. Current challenges associated with these areas as well as opportunities to address long‐standing problems in biology and medicine are discussed throughout.     

On the relevance and requirements of biomaterials

The technological orientation of current medical practice is reflected in the effective utilization of a number of diagnostic and therapeutic devices. Synthetic and natural biomaterials alone or in combination form the basis for development of such devices that are in contact with different tissues. The effect of materials on tissues andvice versa needs to be understood to ensure safety and effectiveness of the devices. This calls for biological evaluation of materials and devices, in addition to a spectrum of recommended toxicological testing of materials depending upon the duration and the type of tissue in contact with. Besides being non-toxic, the material is required to meet the functional requirements with the appropriate host response which is termed as biocompatibility. This paper reviews the evolution and the requirements of biomaterials. Thein vitro andin vivo evolution methodologies are highlighted based on our experience in developing blood bag, dental composite, hydroxyapatite and fibrin glue. The requirements of biomaterials in the current context of advances in the fields of tissue engineering and biomimetics is outlined.     

仿生有序结构羟基磷灰石研究进展

羟基磷灰石(hydroxyapatite,HAP)与人体硬组织主要无机组分具有相同的化学组成,因而被认为具备良好的生物相容性、可降解性和生物活性,并已在生物医学领域得到广泛应用。迄今为止,形态丰富的HAP纳米材料及其合成方法已经被报道出来,但是具有仿生有序结构的HAP材料及其制备方法仍然是相关领域最具挑战性的方向。在包括牙釉质、皮质骨和松质骨在内的硬组织中,纳米尺度的HAP通常会按照人体受力分布情况呈可控有序结构排列。因此,通过仿生天然硬组织微结构实现HAP的可控有序组装,有望进一步提升传统HAP基生物材料的力学和生物学性能。近年来,包括氧化铝模板法、有机溶剂/小分子调控法、磷酸氢钙相转化法、高分子/蛋白分子诱导矿化法、冷冻铸造等在内的HAP有序结构制备方法已经被发展出来,并实现了在纳米、微米等尺度上有序结构的制备。最近,作者课题组报道了HAP纳米线的扩大化溶剂热制备方法,并进一步提出了适用于控制HAP纳米线有序排列的表面小分子介导的液相自组装策略,获得了尺寸和方向均可控的宏观尺度HAP纳米线仿生有序结构。相比于传统无序结构HAP基生物材料,具有仿生有序结构的HAP表现出了良好的力学和生物学性能,对新型无机生物材料的设计、制备及其生物医学应用研究具有重要的指导意义。综述了仿生有序结构HAP的研究进展,包括其结构组成、合成方法及调控机制,最后总结了仿生有序结构HAP研究领域当前面临的挑战以及未来的发展前景。     

纳米生物材料的应用

纳米生物材料是纳米材料和生物材料交叉而成的一个全新领域。纳米尺度的特殊生物效应使得纳米生物材料具有广泛的应用前景。文章按照纳米材料技术在材料领域的最新应用和经典材料的分类方法,对纳米金属生物材料、纳米无机非金属生物材料、纳米高分子生物材料、纳米复合生物材料的研究现状及应用作了综述。     

Ti based biomaterials,the ultimate choice for orthopaedic implants – A review

The field of biomaterials has become a vital area, as these materials can enhance the quality and longevity of human life and the science and technology associated with this field has now led to multi-million dollar business. The paper focuses its attention mainly on titanium-based alloys, even though there exists biomaterials made up of ceramics, polymers and composite materials. The paper discusses the biomechanical compatibility of many metallic materials and it brings out the overall superiority of Ti based alloys, even though it is costlier. As it is well known that a good biomaterial should possess the fundamental properties such as better mechanical and biological compatibility and enhanced wear and corrosion resistance in biological environment, the paper discusses the influence of alloy chemistry, thermomechanical processing and surface condition on these properties. In addition, this paper also discusses in detail the various surface modification techniques to achieve superior biocompatibility, higher wear and corrosion resistance. Overall, an attempt has been made to bring out the current scenario of Ti based materials for biomedical applications.     

Terahertz sources and detectors and their application to biological sensing

Terahertz spectroscopy has long been used as an important measurement tool in fields such as radio astronomy, physical chemistry, atmospheric studies and plasma research. More recently terahertz technology has been used to develop an exciting new technique to investigate the properties of a wide range of biological materials. Although much research remains before a full understanding of the interaction between biomaterials and terahertz radiation is developed, these initial studies have created a compelling case for further scientific study. Also, the potential development of practical tools to detect and identify biological materials such as biological-warfare agents and food contaminants, or of medical diagnostic tools, is driving the need for improved terahertz technology. In particular, improved terahertz sources and detectors that can be used in practical spectroscopy systems are needed. This paper overviews some of the recent measurements of the terahertz spectra of biomaterials and the ongoing efforts to create an all-solid-state technology suitable not only for improved scientific experiments but also for military and commercial applications.     

Colloidal Crystals from Microfluidics

Colloidal crystals are of great interest to researchers because of their excellent optical properties and broad applications in barcodes, sensors, displays, drug delivery, and other fields. Therefore, the preparation of high quality colloidal crystals in large quantities with high speed is worth investigating. After decades of development, microfluidics have been developed that provide new choices for many fields, especially for the generation of functional materials in microscale. Through the design of microfluidic chips, colloidal crystals can be prepared controllably with the advantages of fast speed and low cost. In this Review, research progress on colloidal crystals from microfluidics is discussed. After summarizing the classifications, the generation of colloidal crystals from microfluidics is discussed, including basic colloidal particles preparation, and their assembly inside or outside of microfluidic devices. Then, applications of the achieved colloidal crystals from microfluidics are illustrated. Finally, the future development and prospects of microfluidic‐based colloidal crystals are summarized.     

Tissue-biomaterial interactions

A wide variety of materials is being increasingly used in medical practice for the treatment of patients in which the materials come into direct and often sustained contact with the tissues of the body. The commonly-known examples of hip replacements, contact and intraocular lenses and pace-makers serve to emphasize the importance of this subject. Because the body is so well equipped to reject any intruding object, whether that is a bacterium or a splinter of wood, the materials which are to stand any chance of success within this hostile yet sensitive milieu must be chosen very carefully. The subject of biomaterials represents an almost unique blend of physical and biological sciences, and it is becoming increasingly important that these aspects are drawn together to help in the development of quality biomaterials that are able to perform optimally in this environment. The key to this subject lies in the interactions that take place between biomaterials and these tissues and this review is aimed at providing, for the materials scientist, an understanding of the mechanisms of these interactions.     

复合纳米生物医用材料的研究

生物医用材料领域中,细胞与材料间的相互作用是研究的主要课题.材料表面的微观结构对细胞的生物调控作用更为重要.纳米材料因具有一些独特的效应,如体积效应和表面效应,有利于细胞黏附、增殖和功能表达,因而作为生物医用材料特别是组织工程支架材料具有良好的应用前景.目前用于生物医用研究的纳米材料主要有无机纳米材料、高分子纳米材料以及复合纳米材料等.仿生纳米材料的研究和利用极大地促进了组织工程学的发展.本文就近年来纳米材料在生物医用材料尤其是组织工程支架材料中的应用研究现状进行了综述.     

Multicellular Vascularized Engineered Tissues through User‐Programmable Biomaterial Photodegradation

A photodegradable material‐based approach to generate endothelialized 3D vascular networks within cell‐laden hydrogel biomaterials is introduced. Exploiting multiphoton lithography, microchannel networks spanning nearly all size scales of native human vasculature are readily generated with unprecedented user‐defined 4D control. Intraluminal channel architectures of synthetic vessels are fully customizable, providing new opportunities for next‐generation microfluidics and directed cell function.