Strategies for organ level tissue engineering

The field of tissue engineering has made considerable strides since it was first described in the late 1980s. The advent and subsequent boom in stem cell biology, emergence of novel technologies for biomaterial development, and further understanding of developmental biology have contributed to this accelerated progress. However, continued efforts to translate tissue engineering strategies into clinical therapies have been hampered by the problems associated with scaling up laboratory methods to produce large, complex tissues. The significant challenges faced by tissue engineers include the production of an intact vasculature within a tissue-engineered construct and recapitulation of the size and complexity of a whole organ. Here we review the basic components necessary for bioengineering organs – biomaterials, cells and bioactive molecules–and discuss various approaches for augmenting these principles to achieve organ level tissue engineering. Ultimately, the successful translation of tissue-engineered constructs into everyday clinical practice will depend upon the ability of the tissue engineer to “scale up” every aspect of the research and development process.     

Strategies for tissue and organ decellularization

Decellularized tissues have been successfully used in a variety of tissue engineering/regenerative medicine applications, and more recently decellularized organs have been utilized in the first stages of organ engineering. The protocols used to decellularize simple tissues versus intact organs differ greatly. Herein, the most commonly used decellularization methods for both surgical mesh materials and whole organs are described, with consideration given to how these different processes affect the extracellular matrix and the host response to the scaffold.     

基于组织工程研究的可降解支架材料选择策略

目前,器官或组织移植是治疗器官衰竭或大范围组织缺损唯一长期有效的方法,但存在供体短缺、免疫排斥等问题。组织工程技术作为一种潜在的替代治疗方法,支架材料的选择是其中具有决定意义的组成部分。组织工程支架材料按其来源可分为天然及其改性修饰材料、人工合成与复合支架材料3种。组织工程目的就是修复临床上的病损组织或器官,并达到较理想的结构和功能的恢复。因此组织工程支架也必须从基本性质上具有一定的仿生化结构及功能,即"活"支架,这样才能彻底代替病损组织或器官。通过多种支架材料的优化组合(即材料的复合),对材料进行表面改性、制备工艺优化及添加细胞因子缓释微球等技术,模拟病损器官组织的特性及周围环境,有望打开组织工程的新局面。理想的组织工程支架应当以临床需要为根本目的,依靠材料学、分子生物学、工程学等多学科间的交叉研究,取各家之长,优化配比组合,达到仿生的目的。本课题组前期工作已经将骨髓间充质干细胞体外诱导分化为胆管上皮样细胞,并设计出左旋聚乳酸/聚己内酯共聚物(PLCL)胆道支架,内部混有包含生长因子的纳米缓释微球,供细胞因子的远期释放,支架内表面涂有基质胶/胶原混合层,且胶内加入bFGF、EGF,提供诱导因子的早期释放。将诱导细胞与PLCL胆道支架复合,制备组织工程胆管。文中综述了现存各类支架材料的研究状况,简单介绍了制备工艺、表面修饰等影响支架性能的因素,力求探索组织工程支架材料的选择策略。     

Strategies on process engineering of chondrocyte culture for cartilage tissue regeneration

Bioprocess and Biosystems Engineering - The current work is an attempt to study the strategies for cartilage tissue regeneration using porous scaffold in wavy walled airlift bioreactor (ALBR)....     

Hair follicular cell/organ culture in tissue engineering and regenerative medicine

Hair follicles are complex organs composed of the dermal papilla (DP), dermal sheath (DS), outer root sheath (ORS), inner root sheath (IRS) and hair shaft. Development of hair follicles begins towards the end of the first trimester of pregnancy and is controlled by epidermal–mesenchymal interaction (EMI), which is a signaling cascade between epidermal and mesenchymal cell populations. Hair grows in cycles of various phases. Specifically, anagen is the growth phase, catagen is the involuting or regressing phase and telogen is the resting or quiescent phase. Alopecia is not life threatening, but alopecia often causes severe mental stress. In addition, the number of individuals afflicted by alopecia patients has been increasing steadily. Currently there are two methods employed to treat alopecia, drug or natural substance therapy and human hair transplantation. Although drug or natural substance therapy may retard the progress of alopecia or prevent future hair loss, it may also accelerate hair loss when the medication is stopped after prolonged use. Conversely, the transplantation of human hair involves taking plugs of natural hair from areas in which occipital hair is growing and transplanting them to bald areas. However, the number of hairs that can be transplanted is limited in that only three such operations can generally be performed. To overcome such problems, many researchers have attempted to revive hair follicles by culturing hair follicle cells or mesenchymal cells in vitro and then implanting them in the treatment area.     

Cells for tissue engineering

Recent advances in stem-cell technology have improved the prognosis for tissue engineering. The use of cultured stem and/or progenitor cells has the potential to improve the extent of regeneration, and also increases the likelihood that the transplanted tissue will integrate with the surrounding tissue. It could eventually even reduce or eliminate the need for immunosuppressive drugs.     

Bioreactors for tissue engineering

Bioreactors are essential in tissue engineering, not only because they provide an in vitro environment mimicking in vivo conditions for the growth of tissue substitutes, but also because they enable systematic studies of the responses of living tissues to various mechanical and biochemical cues. The basic principles of bioreactor design are reviewed, the bioreactors commonly used for the tissue engineering of cartilage, bone and cardiovascular systems are assessed in terms of their performance and usefulness. Several novel bioreactor types are also reviewed.     

Strategies for systems-level metabolic engineering

Bio-based production of chemicals, fuels and materials is becoming more and more important due to the increasing environmental problems and sharply increasing oil price. To make these biobased processes economically competitive, the biotechnology industry explores new ways to improve the performance of microbial strains in fermentation processes. In contrast to the random mutagenesis and/or intuitive local metabolic engineering practiced in the past, we are now moving towards global-scale metabolic engineering, aided by various experimental and computational tools. This has recently led to some remarkable achievements for the overproduction of valueadded products. In this review, we highlight several relevant gene manipulation tools and computational tools using genome-scale stoichiometric models, and provide useful strategies for successful metabolic engineering along with selected exemplary studies.     

几丁聚糖在组织工程中的应用

支架材料作为组织工程的生物学植入替代物,对细胞移植与引导新组织生长有重要的作用。几丁聚糖可制成无毒性,无刺激性,生物相容性和生物可降解性良好的生物医用材料,在人工皮肤,骨修复材料,手术缝线等方面已广泛应用。本文分析了纯几丁聚糖支架结构和它与其他天然或合成材料复合的支架结构的物理、化学性质及其独特的生物学功能,同时还进一步介绍了其应用的范例并探讨了发展前景。     

Collagen scaffolds for tissue engineering

There are two major approaches to tissue engineering for regeneration of tissues and organs. One involves cell-free materials and/or factors and one involves delivering cells to contribute to the regeneraion process. Of the many scaffold materials being investigated, collagen type I, with selective removal of its telopeptides, has been shown to have many advantageous features for both of these approaches. Highly porous collagen lattice sponges have been used to support in vitro growth of many types of tissues. Use of bioreactors to control in vitro perfusion of medium and to apply hydrostatic fluid pressure has been shown to enhance histogenesis in collagen scaffolds. Collagen sponges have also been developed to contain differentiating-inducing materials like demineralized bone to stimulate differentiation of cartilage tissue both in vitro and in vivo.     

组织工程支架材料

用于组织工程支架构建的生物材料,分为胶原、多糖、无机及生物衍生物等天然材料和聚酯、聚氨基酸、聚乙二醇等人工合成可生物降解材料两大类,此文分别对它们的研究进行了综述。     

Nanoparticles for bone tissue engineering

Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches ‐ such as drug delivery and cell labeling ‐ within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590–611, 2017     

Enabling tools for tissue engineering

Tissue engineering is a multidisciplinary field that combines engineering, physical sciences, biology, and medicine to restore or replace tissues and organs functions. In this review, enabling tools for tissue engineering are discussed in the context of four key areas or pillars: prediction, production, performance, and preservation. Prediction refers to the computational modeling where the ability to simulate cellular behavior in complex three-dimensional environments will be essential for design of tissues. Production refer imaging modalities that allow high resolution, non-invasive monitoring of the development and incorporation of tissue engineered constructs. Lastly, preservation includes biochemical tools that permit cryopreservation, vitrification, and freeze-drying of cells and tissues. Recent progress and future perspectives for development in each of these key areas are presented.     

Epithelial machines of morphogenesis and their potential application in organ assembly and tissue engineering

Sheets of embryonic epithelial cells coordinate their efforts to create diverse tissue structures such as pits, grooves, tubes, and capsules that lead to organ formation. Such cells can use a number of cell behaviors including contractility, proliferation, and directed movement to create these structures. By contrast, tissue engineers and researchers in regenerative medicine seeking to produce organs for repair or replacement therapy can combine cells with synthetic polymeric scaffolds. Tissue engineers try to achieve these goals by shaping scaffold geometry in such a way that cells embedded within these scaffold self-assemble to form a tissue, for instance aligning to synthetic fibers, and assembling native extracellular matrix to form the desired tissue-like structure. Although self-assembly is a dominant process that guides tissue assembly both within the embryo and within artificial tissue constructs, we know little about these critical processes. Here, we compare and contrast strategies of tissue assembly used by embryos to those used by engineers during epithelial morphogenesis and highlight opportunities for future applications of developmental biology in the field of tissue engineering.     

糖苷酶耐热性改造策略与应用

糖苷酶作为绿色温和的生物催化剂,能够水解包含糖苷、寡糖、多糖等在内的各种含糖化合物的糖苷键生成具有高生理和药理活性的衍生物,在食品、医药等工业领域应用广泛.而工业应用的糖苷酶经常需在高温条件下进行催化,以提高反应效率并减少污染,但大多数糖苷酶属于中温酶,在实际生产条件下的活性较低且损失较快,因此,提高糖苷酶在高温下的稳...     

Dielectrophoresis based-cell patterning for tissue engineering

Engineering functional tissues and organs in vitro is considered integral to regenerative medicine. Many recent cell patterning technique developments position cells at a pre-designated pattern to improve tissue engineering efficiency and quality and to facilitate 3-D cell-cell interaction exploration. Among these techniques, dielectrophoresis (DEP)-based cell patterning advantageously offers speed, ease of operation, low degree of cell damage, and precision. This article reviews recent advances in DEP-based patterning techniques, including electrode design, suitable buffer and hydrogel, effects of the electric current to cells, combination potential with other techniques, as well as efforts to generate 3-D tissues.     

Yarn design for functional tissue engineering

Tissue engineering requires the ability to design scaffolds with mechanical properties similar to those of the native tissue. Here, B. mori silk yarns are used as a model system to demonstrate the potential benefits and drawbacks of several textile methods used to fabricate tissue engineering scaffolds. Fibers are plied, twisted, cabled, braided, and/or textured to form several geometries with a wide range of mechanical outcomes. Predictable changes in ultimate tensile strength and stiffness are demonstrated following processing and as a function of test environment. The mechanical effects of increasing turns per inch and combining groups of fibers into higher-order yarn structures are demonstrated. Braids, one of the most commonly used textile structures, are shown to be limited by a change in stiffness following the locking-angle and therefore, potentially not the ideal structure for tissue engineering. Cabled yarns appear to allow the most flexibility in mechanical outcomes with a highly organized geometry. Twisted yarns, while more economical than cabled yarns, result in a higher stiffness and lower percent elongation at break than cabled yarns.     

Multiscale tissue engineering for liver reconstruction

The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies.