丝素蛋白水凝胶材料在组织工程中的应用研究进展

组织工程技术是有望从根本上解决组织或器官损伤及实现功能重建的前沿技术,其关键之一是制备具有良好生物相容性和生物降解性的支架材料。水凝胶由于具有众多良好的特性,成为组织工程研究中一种优良的支架材料。丝素蛋白水凝胶由于独特的性质、多样化的成胶方式以及优异的可加工性成为了支架材料研究的热点,备受学者的青睐并涌现出了大量的研究成果。本文在阐明丝素蛋白凝胶原理的基础上,回顾了目前较为成熟的凝胶化方法,随后重点综述了丝素蛋白水凝胶在组织工程中的研究进展,最后进行了总结和展望,以期为相关领域的研究者提供参考和借鉴。     

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs‐on‐a‐chip (OOC), evolved from developmental biology and bioengineering principles, have emerged as major technological breakthrough and distinct model systems to revolutionize biomedical research and drug discovery by recapitulating the key structural and functional complexity of human organs in vitro. There is growing interest in the development of functional biomaterials, especially hydrogels, for utilization in these promising systems to build more physiologically relevant 3D tissues with defined properties. The remarkable properties of defined hydrogels as proper extracellular matrix that can instruct cellular behaviors are presented. The recent trend where functional hydrogels are integrated into organoids and OOC systems for the construction of 3D tissue models is highlighted. Future opportunities and perspectives in the development of advanced hydrogels toward accelerating organoids and OOC research in biomedical applications are also discussed.     

Engineering of Hydrogel Materials with Perfusable Microchannels for Building Vascularized Tissues

Vascular systems are responsible for various physiological and pathological processes related to all organs in vivo, and the survival of engineered tissues for enough nutrient supply in vitro. Thus, biomimetic vascularization is highly needed for constructing both a biomimetic organ model and a reliable engineered tissue. However, many challenges remain in constructing vascularized tissues, requiring the combination of suitable biomaterials and engineering techniques. In this review, the advantages of hydrogels on building engineered vascularized tissues are discussed and recent engineering techniques for building perfusable microchannels in hydrogels are summarized, including micromolding, 3D printing, and microfluidic spinning. Furthermore, the applications of these perfusable hydrogels in manufacturing organ‐on‐a‐chip devices and transplantable engineered tissues are highlighted. Finally, current challenges in recapitulating the complexity of native vascular systems are discussed and future development of vascularized tissues is prospected.     

人工骨的快速成形制造

应用组织工程材料制造的人工骨能够适时降解并诱导成形,而成为最理想的骨组织人工替代方法。采用快速成形（ＲＰ）技术制造人体骨,此法得到的人工骨在材料种类,微观组织结构和生理功能等方面均与人骨高度相似,而采用骨水泥,或含有烧结等步骤,将不具有这种相似性,人骨生长因子（ＢＭＰ）的复合通过特殊处理、使之达到多维复合,并且具有缓释功效,大大有利于愈合。     

Molecular communication and networking: opportunities and challenges

The ability of engineered biological nanomachines to communicate with biological systems at the molecular level is anticipated to enable future applications such as monitoring the condition of a human body, regenerating biological tissues and organs, and interfacing artificial devices with neural systems. From the viewpoint of communication theory and engineering, molecular communication is proposed as a new paradigm for engineered biological nanomachines to communicate with the natural biological nanomachines which form a biological system. Distinct from the current telecommunication paradigm, molecular communication uses molecules as the carriers of information; sender biological nanomachines encode information on molecules and release the molecules in the environment, the molecules then propagate in the environment to receiver biological nanomachines, and the receiver biological nanomachines biochemically react with the molecules to decode information. Current molecular communication research is limited to small-scale networks of several biological nanomachines. Key challenges to bridge the gap between current research and practical applications include developing robust and scalable techniques to create a functional network from a large number of biological nanomachines. Developing networking mechanisms and communication protocols is anticipated to introduce new avenues into integrating engineered and natural biological nanomachines into a single networked system. In this paper, we present the state-of-the-art in the area of molecular communication by discussing its architecture, features, applications, design, engineering, and physical modeling. We then discuss challenges and opportunities in developing networking mechanisms and communication protocols to create a network from a large number of bio-nanomachines for future applications.     

Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to ‘conventional’ methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions.     

Nanotechnological strategies for engineering complex tissues

Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering.     

输电塔线体系力学模型研究进展

输电塔线体系是重要的电力能源基础设施,长期于野外恶劣环境下服役,其高柔特性使得它在强烈外荷载作用下的响应较为显著。国内外发生了很多输电线路在强风强震、覆冰、腐蚀等作用下的破坏事故,造成了严重的损失。因此,国内外积极开展了输电线路的监测评估与防灾减灾的研究和工程应用工作。输电塔线体系力学模型的建立是开展输电线路监测评估和防灾减灾的基础和关键。输电线从力学角度而言是具有小应变、大变形特征的悬索,表现出显著的几何非线性效应。输电塔线体系的力学模型相比于传统高耸塔架结构而言非常复杂,它综合了有限元、随机振动、变分理论、风工程、地震工程、结构分析理论等多学科理论,相关研究工作还不完善。该文以输电塔线体系的力学模型为研究对象,全面综述了目前塔线体系力学模型方面的研究现状,对比分析了不同模型的优缺点,总结了该研究方面存在的不足并就将来的发展进行了展望。     

Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends.

The fields of tissue engineering and regenerative medicine aim at promoting the regeneration of tissues or replacing failing or malfunctioning organs, by means of combining a scaffold/support material, adequate cells and bioactive molecules. Different materials have been proposed to be used as both three-dimensional porous scaffolds and hydrogel matrices for distinct tissue engineering strategies. Among them, polymers of natural origin are one of the most attractive options, mainly due to their similarities with the extracellular matrix (ECM), chemical versatility as well as typically good biological performance. In this review, the most studied and promising and recently proposed naturally derived polymers that have been suggested for tissue engineering applications are described. Different classes of such type of polymers and their blends with synthetic polymers are analysed, with special focus on polysaccharides and proteins, the systems that are more inspired by the ECM. The adaptation of conventional methods or non-conventional processing techniques for processing scaffolds from natural origin based polymers is reviewed. The use of particles, membranes and injectable systems from such kind of materials is also overviewed, especially what concerns the present status of the research that should lead towards their final application. Finally, the biological performance of tissue engineering constructs based on natural-based polymers is discussed, using several examples for different clinically relevant applications.     

Peptide and Protein Presenting Materials for Tissue Engineering

Tissue engineering aims to create new tissues and organs to replace those lost to disease, trauma, or congenital defects. However, considerable instruction must be given to the cells forming these new tissues if one is to create a tissue structurally and functionally similar to the native tissue. Materials are ideal for the local presentation of various peptides and proteins that can bind to cell surface receptors and regulate cell function. An overview of techniques to present peptides and proteins from materials, and the utility of these systems in engineering tissues in vitro and in vivo is presented.     

Promising perspectives towards regrowing a human arm

Despite the great enthusiasm about tissue engineering during the 1980s and the many significant basic observations made since then, the clinical application of tissue-engineered products has been limited. However, the prospect of creating new human tissues and organs is still exciting and continues to be a significant challenge for scientists and clinicians. A human arm is an extremely complicated biological construction. Considering regrowing a human arm requires asking about the current state-of-the-art of tissue engineering and the real capabilities that it may offer within a realistic time horizon. This work briefly addresses the state-of-the-art in the fields of cells and scaffolds that have high regenerative potential. Additional tools that are required to reconstruct more complex parts of the body, such as a human arm, seem achievable with the already available more sophisticated culture systems including three-dimensional organization, dynamic conditions and co-cultures. Finally, we present results on cell differentiation and cell and tissue maturation in culture when cells are exposed to mechanical forces. We postulate that in the foreseeable future even such complicated structures such as a human arm will be regrown in full in vitro under the conditions of a mechanically controlled co-culture system.     

Flexible and Stretchable Antennas for Biointegrated Electronics

Combined advances in material science, mechanical engineering, and electrical engineering form the foundations of thin, soft electronic/optoelectronic platforms that have unique capabilities in wireless monitoring and control of various biological processes in cells, tissues, and organs. Miniaturized, stretchable antennas represent an essential link between such devices and external systems for control, power delivery, data processing, and/or communication. Applications typically involve a demanding set of considerations in performance, size, and stretchability. Some of the most effective strategies rely on unusual materials such as liquid metals, nanowires, and woven textiles or on optimally configured 2D/3D structures such as serpentines and helical coils of conventional materials. In the best cases, the performance metrics of small, stretchable, radio frequency (RF) antennas realized using these strategies compare favorably to those of traditional devices. Examples range from dipole, monopole, and patch antennas for far-field RF operation, to magnetic loop antennas for near-field communication (NFC), where the key parameters include operating frequency, Q factor, radiation pattern, and reflection coefficient S₁₁ across a range of mechanical deformations and cyclic loads. Despite significant progress over the last several years, many challenges and associated research opportunities remain in the development of high-efficiency antennas for biointegrated electronic/optoelectronic systems.     

A review on powder-based additive manufacturing for tissue engineering: selective laser sintering and inkjet 3D printing

Since most starting materials for tissue engineering are in powder form, using powder-based additive manufacturing methods is attractive and practical. The principal point of employing additive manufacturing (AM) systems is to fabricate parts with arbitrary geometrical complexity with relatively minimal tooling cost and time. Selective laser sintering (SLS) and inkjet 3D printing (3DP) are two powerful and versatile AM techniques which are applicable to powder-based material systems. Hence, the latest state of knowledge available on the use of AM powder-based techniques in tissue engineering and their effect on mechanical and biological properties of fabricated tissues and scaffolds must be updated. Determining the effective setup of parameters, developing improved biocompatible/bioactive materials, and improving the mechanical/biological properties of laser sintered and 3D printed tissues are the three main concerns which have been investigated in this article.     

Liposomes in tissue engineering and regenerative medicine

Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches.     

Impact of Scaffold Micro and Macro Architecture on Schwann Cell Proliferation under Dynamic Conditions in a Rotating Wall Vessel Bioreactor

Over the last decade tissue engineering has emerged as a powerful alternative to regenerate lost tissues owing to trauma or tumor. Evidence shows that Schwann cell containing scaffolds have improved performance in vivo as compared to scaffolds that depend on cellularization post implantation. However, owing to limited supply of cells from the patients themselves, several approaches have been taken to enhance cell proliferation rates to produce complete and uniform cellularization of scaffolds. The most common approach is the application of a bioreactor to enhance cell proliferation rate and therefore reduce the time needed to obtain sufficiently significant number of glial cells, prior to implantation.In this study, we show the application of a rotating wall bioreactor system for studying Schwann cell proliferation on nanofibrous spiral shaped scaffolds, prepared by solvent casting and salt leaching techniques. The scaffolds were fabricated from polycaprolactone (PCL), which has ideal mechanical properties and upon degradation does not produce acidic byproducts. The spiral scaffolds were coated with aligned or random nanofibers, produced by electrospinning, to provide a substrate that mimics the native extracellular matrix and the essential contact guidance cues.At the 4 day time point, an enhanced rate of cell proliferation was observed on the open structured nanofibrous spiral scaffolds in a rotating wall bioreactor, as compared to static culture conditions. However, the cell proliferation rate on the other contemporary scaffolds architectures such as the tubular and cylindrical scaffolds show reduced cell proliferation in the bioreactor as compared to static conditions, at the same time point. Moreover, the rotating wall bioreactor does not alter the orientation or the phenotype of the Schwann cells on the aligned nanofiber containing scaffolds, wherein, the cells remain aligned along the length of the scaffolds. Therefore, these open structured spiral scaffolds pre-cultured with Schwann cells, in bioreactors could potentially shorten the time needed for grafts for peripheral nerve regeneration.     

A review on powder-based additive manufacturing for tissue engineering: selective laser sintering and inkjet 3D printing

Abstract

Since most starting materials for tissue engineering are in powder form, using powder-based additive manufacturing methods is attractive and practical. The principal point of employing additive manufacturing (AM) systems is to fabricate parts with arbitrary geometrical complexity with relatively minimal tooling cost and time. Selective laser sintering (SLS) and inkjet 3D printing (3DP) are two powerful and versatile AM techniques which are applicable to powder-based material systems. Hence, the latest state of knowledge available on the use of AM powder-based techniques in tissue engineering and their effect on mechanical and biological properties of fabricated tissues and scaffolds must be updated. Determining the effective setup of parameters, developing improved biocompatible/bioactive materials, and improving the mechanical/biological properties of laser sintered and 3D printed tissues are the three main concerns which have been investigated in this article.     

Organ-Level Functional 3D Tissue Constructs with Complex Compartments and their Preclinical Applications

There is an increasing interest in organ-level 3D tissue constructs, owing to their mirroring of in vivo-like features. This has resulted in a wide range of preclinical applications to obtain cell- or tissue-specific responses. Additionally, the development and improvement of sophisticated technologies, such as organoid generation, microfluidics, hydrogel engineering, and 3D printing, have enhanced 3D tissue constructs to become more elaborate. In particular, recent studies have focused on including complex compartments, i.e., vascular and innervation structured 3D tissue constructs, which mimic the nature of the human body in that all tissues/organs are interconnected and physiological phenomena are mediated through vascular and neural systems. Here, the strategies are categorized according to the number of dimensions (0D, 1D, 2D, and 3D) of the starting materials for scaling up, and novel approaches to introduce increased complexity in 3D tissue constructs are highlighted. Recent advances in preclinical applications are also investigated to gain insight into the future direction of 3D tissue construct research. Overcoming the challenges in improving organ-level functional 3D tissue constructs both in vitro and in vivo will ultimately become a life-saving tool in the biomedical field.     

Self-assembly of mineralized collagen composites

This paper presents a review of the current understanding of the structure, self-assembly mechanisms, and properties of mineralized collagen fibril composites in connective tissues, such as in lamellar bones, woven bones, zebrafish skeletal bone, and ivory. Recent work involving biomimetic synthesis of new materials with the structure of mineralized collagen is described. The focus in the paper is mainly on materials containing type I collagen, with mineralization by Ca–P crystals although some other systems are also described. Investigation and simulation of naturally occurring fibril structures can offer some new ideas in the design and fabrication of new functional materials, for applications such as bone grafts or for use as scaffolds in tissue engineering and biomimetic engineering materials. The development of bone grafts based on the mineralization of self-assembled collagen fibrils in vivo and in vitro is an active area of research. This kind of bone graft composite has already shown great promise and success in clinical applications, on account of its compositional and structural similarity to autologous bone. It is suggested that future work in this should focus on both basic theoretical aspects as well as the development of applications. In particular issues including control of morphology, incorporation of foreign ions, interaction with biomolecules, and the assembly of organic and inorganic phases are all still not well understood. In the area of applications, the design of composite materials with a hierarchical structure closer to that of natural hard tissues, and the synthesis of bone grafts and tooth regenerative materials, as well as biomimetic functional materials, are areas currently being examined by many research groups.     

Electrospun composite nanofibers for tissue regeneration

Nanotechnology assists in the development of biocomposite nanofibrous scaffolds that can react positively to changes in the immediate cellular environment and stimulate specific regenerative events at molecular level to generate healthy tissues. Recently, electrospinning has gained huge momentum with greater accessibility of fabrication of composite, controlled and oriented nanofibers with sufficient porosity required for effective tissue regeneration. Current developments include the fabrication of nanofibrous scaffolds which can provide chemical, mechanical and biological signals to respond to the environmental stimuli. These nanofibers are fabricated by simple coating, blending of polymers/bioactive molecules or by surface modification methods. For obtaining optimized surface functionality, with specially designed architectures for the nanofibers (multi-layered, core-shell, aligned), electrospinning process has been modified and simultaneous 'electrospin-electrospraying' process is one of the most lately introduced technique in this perspective. Properties such as porosity, biodegradation and mechanical properties of composite electrospun nanofibers along with their utilization for nerve, cardiac, bone, skin, vascular and cartilage tissue engineering are discussed in this review. In order to locally deliver electrical stimulus and provide a physical template for cell proliferations, and to gain an external control on the level and duration of stimulation, electrically conducting polymeric nanofibers are also fabricated by electrospinning. Electrospun polypyrrole (PPy) and polyaniline (PAN) based scaffolds are the most extensively studied composite substrates for nerve and cardiac tissue engineering with or without electrical stimulations, and are discussed here. However, the major focus of ongoing and future research in regenerative medicine is to effectively exploit the pluripotent potential of Mesenchymal Stem Cell (MSC) differentiation on composite nanofibrous scaffolds for repair of organs.