Gene therapy and tissue engineering for sports medicine

Sports injuries usually involve tissues that display a limited capacity for healing. The treatment of sports injuries has improved over the past 10 to 20 years through sophisticated rehabilitation programs, novel operative techniques, and advances in the field of biomechanical research. Despite this considerable progress, no optimal solution has been found for treatment of various sports-related injuries, including muscle injuries, ligament and tendon ruptures, central meniscal tears, cartilage lesions, and delayed bone fracture healing. New biological approaches focus on the treatment of these injuries with growth factors to stimulate and hasten the healing process. Gene therapy using the transfer of defined genes encoding therapeutic proteins represents a promising way to efficiently deliver suitable growth factors into the injured tissue. Tissue engineering, which may eventually be combined with gene therapy, may potentially result in the creation of tissues or scaffolds for regeneration of tissue defects following trauma. In this article we will discuss why gene therapy and tissue engineering are becoming increasingly important in modern orthopaedic sports medicine practice. We then will review recent research achievements in the area of gene therapy and tissue engineering for sports-related injuries, and highlight the potential clinical applications of this technology in the treatment of patients with musculoskeletal problems following sports-related injuries.     

Tissue engineering in otorhinolaryngology

Tissue engineering is a field of research with interdisciplinary cooperation between clinicians, cell biologists, and materials research scientists. Many medical specialties apply tissue engineering techniques for the development of artificial replacement tissue. Stages of development extend from basic research and preclinical studies to clinical application. Despite numerous established tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue engineering techniques opens up new ways for cell and tissue repair in this medical field. Autologous cartilage still remains the gold standard in plastic reconstructive surgery of the nose and external ear. The limited amount of patient cartilage obtainable for reconstructive head and neck surgery have rendered cartilage one of the most important targets for tissue engineering in head and neck surgery. Although successful in vitro generation of bioartificial cartilage is possible today, these transplants are affected by resorption after implantation into the patient. Replacement of bone in the facial or cranial region may be necessary after tumor resections, traumas, inflammations or in cases of malformations. Tissue engineering of bone could combine the advantages of autologous bone grafts with a minimal requirement for second interventions. Three different approaches are currently available for treating bone defects with the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based therapy, and (3) cell-based therapy. All three treatment strategies can be used either alone or in combination for reconstruction or regeneration of bone. The use of respiratory epithelium generated in vitro is mainly indicated in reconstructive surgery of the trachea and larynx. Bioartificial respiratory epithelium could be used for functionalizing tracheal prostheses as well as direct epithelial coverage for scar prophylaxis after laser surgery of shorter stenoses. Before clinical application animal experiments have to prove feasability and safety of the different experimental protocols. All diseases accompanied by permanently reduced salivation are possible treatment targets for tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head and neck tumors is of particular importance here due to the high number of affected patients. The number of new diseases is estimated to be over 500,000 cases worldwide. Causal treatment options for radiation-induced salivary gland damage are not yet available; thus, various study groups are currently investigating whether cell therapy concepts can be developed with tissue engineering methods. Tissue engineering opens up new ways to generate vital and functional transplants. Various basic problems have still to be solved before clinically applying in vitro fabricated tissue. Only a fraction of all somatic organ-specific cell types can be grown in sufficient amounts in vitro. The inadequate in vitro oxygen and nutrition supply is another limiting factor for the fabrication of complex tissues or organ systems. Tissue survival is doubtful after implantation, if its supply is not ensured by a capillary network.     

Osteochondral tissue engineering: Current strategies and challenges

Osteochondral defect management and repair remain a significant challenge in orthopedic surgery. Osteochondral defects contain damage to both the articular cartilage as well as the underlying subchondral bone. In order to repair an osteochondral defect the needs of the bone, cartilage and the bone-cartilage interface must be taken into account. Current clinical treatments for the repair of osteochondral defects have only been palliative, not curative. Tissue engineering has emerged as a potential alternative as it can be effectively used to regenerate bone, cartilage and the bone-cartilage interface. Several scaffold strategies, such as single phase, layered, and recently graded structures have been developed and evaluated for osteochondral defect repair. Also, as a potential cell source, tissue specific cells and progenitor cells are widely studied in cell culture models, as well with the osteochondral scaffolds in vitro and in vivo. Novel factor strategies being developed, including single factor, multi-factor, or controlled factor release in a graded fashion, not only assist bone and cartilage regeneration, but also establish osteochondral interface formation. The field of tissue engineering has made great strides, however further research needs to be carried out to make this strategy a clinical reality. In this review, we summarize current tissue engineering strategies, including scaffold design, bioreactor use, as well as cell and factor based approaches and recent developments for osteochondral defect repair. In addition, we discuss various challenges that need to be addressed in years to come.     

Repair of injured articular and growth plate cartilage using mesenchymal stem cells and chondrogenic gene therapy

Injuries to the articular cartilage and growth plate are significant clinical problems due to their limited ability to regenerate themselves. Despite progress in orthopedic surgery and some success in development of chondrocyte transplantation treatment and in early tissue-engineering work, cartilage regeneration using a biological approach still remains a great challenge. In the last 15 years, researchers have made significant advances and tremendous progress in exploring the potentials of mesenchymal stem cells (MSCs) in cartilage repair. These include (a) identifying readily available sources of and devising appropriate techniques for isolation and culture expansion of MSCs that have good chondrogenic differentiation capability, (b) discovering appropriate growth factors (such as TGF-beta, IGF-I, BMPs, and FGF-2) that promote MSC chondrogenic differentiation, (c) identifying or engineering biological or artificial matrix scaffolds as carriers for MSCs and growth factors for their transplantation and defect filling. In addition, representing another new perspective for cartilage repair is the successful demonstration of gene therapy with chondrogenic growth factors or inflammatory inhibitors (either individually or in combination), either directly to the cartilage tissue or mediated through transducing and transplanting cultured chondrocytes, MSCs or other mesenchymal cells. However, despite these rapid pre-clinical advances and some success in engineering cartilage-like tissue and in repairing articular and growth plate cartilage, challenges of their clinical translation remain. To achieve clinical effectiveness, safety, and practicality of using MSCs for cartilage repair, one critical investigation will be to examine the optimal combination of MSC sources, growth factor cocktails, and supporting carrier matrixes. As more insights are acquired into the critical factors regulating MSC migration, proliferation and chondrogenic differentiation both ex vivo and in vivo, it will be possible clinically to orchestrate desirable repair of injured articular and growth plate cartilage, either by transplanting ex vivo expanded MSCs or MSCs with genetic modifications, or by mobilising endogenous MSCs from adjacent source tissues such as synovium, bone marrow, or trabecular bone.     

Mesenchymal stem cells in arthritic diseases

Mesenchymal stem cells (MSCs), the nonhematopoietic progenitor cells found in various adult tissues, are characterized by their ease of isolation and their rapid growth in vitro while maintaining their differentiation potential, allowing for extensive culture expansion to obtain large quantities suitable for therapeutic use. These properties make MSCs an ideal candidate cell type as building blocks for tissue engineering efforts to regenerate replacement tissues and repair damaged structures as encountered in various arthritic conditions. Osteoarthritis (OA) is the most common arthritic condition and, like rheumatoid arthritis (RA), presents an inflammatory environment with immunological involvement and this has been an enduring obstacle that can potentially limit the use of cartilage tissue engineering. Recent advances in our understanding of the functions of MSCs have shown that MSCs also possess potent immunosuppression and anti-inflammation effects. In addition, through secretion of various soluble factors, MSCs can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in situ. This function of MSCs can be exploited for their therapeutic application in degenerative joint diseases such as RA and OA. This review surveys the advances made in the past decade which have led to our current understanding of stem cell biology as relevant to diseases of the joint. The potential involvement of MSCs in the pathophysiology of degenerative joint diseases will also be discussed. Specifically, we will explore the potential of MSC-based cell therapy of OA and RA by means of functional replacement of damaged cartilage via tissue engineering as well as their anti-inflammatory and immunosuppressive activities.     

Evaluation of biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering--a systematic review of the literature

The term tissue engineering is the technology that combines cells, engineering and biological/synthetic material in order to repair, replace or regenerate biological tissues such as bone, muscle, tendons and cartilage. The major human applications of tissue engineering are: skin, bone, cartilage, corneas, blood vessels, left mainstem bronchus and urinary structures. In this systematic review several criteria were identified as the most desirable characteristics of an ideal scaffold. These state that an ideal scaffolds needs to be biodegradable, possess mechanical strength, be highly porous, biocompatible, non-cytotoxic, non antigentic, stuitable for cell attachment, proliferation and differentiation, flexible and elastic, three dimensional, osteoconductive and support the transport of nutrients and metabolic waste. Subsequently, studies reporting on the various advantages and disadvantages of using collagen based scaffolds in musculoskeletal and cartilage tissue engineering were identified. The purpose of this review is to 1) provide a list of ideal characteristics of a scaffold as identified in the literature 2) identify different types of biological protein-based collagen scaffolds used in musculoskeletal and cartilage tissue engineering 3) assess how many of the criteria each scaffold type meets 4) weigh different scaffolds against each other according to their relative properties and shortcomings. The rationale behind this approach is that the ideal scaffold material has not yet been identified. Hence, this review will define how many of the identified ideal characteristics are fulfilled by natural collagen-based scaffolds and address the shortcomings of its use as found in the literature.     

Emergence of chondrogenic progenitor stem cells in transplantation biology-prospects and drawbacks

Avascular tissues such as a cartilage contains a unique type of cell called as the chondrocyte. We, however, have not understood the origin of the chondrocyte population and how this population is maintained in the normal tissue. In spite of being considered to be a simple tissue, scientist had always faced difficulties to engineer this tissue. This is because different structural regions of the articular cartilage were never understood. In addition to this, the limited self-repair potential of cartilage tissue and lack of effective therapeutic options for the treatment of damaged cartilage has remained an unsolved problem. Mesenchymal stem cell based therapy may provide a solution for cartilage regeneration. This is due to their ability to differentiate into chondrogenic lineage when appropriate conditions are provided. An ideal cell source, a three-dimensional cell culture, a suitable scaffold material that accomplishes all the necessary properties and bioactive factors in specific amounts are required to induce chondrocyte differentiation and proliferation. Cartilage tissue engineering is a promising and rapidly expanding area of research that assures cartilage regeneration. However, many unsolved questions concerning the mechanism of engraftment of chondrocytes following transplantation in vivo, biological safety after transplantation and the retention of these cells for lifetime remain to be addressed that is possible only through years of extensive research. Further studies are therefore required to estimate the long-term sustainability of these cells in the native tissue, to identify well suited delivery materials and to have a thorough understanding of the mechanism of interaction between the chondrocytes and extracellular matrix and time is not far when this cell based therapy will provide a comprehensive cure to cartilage disease.     

Functional tissue engineering of chondral and osteochondral constructs

Due to the prevalence of osteoarthritis (OA) and damage to articular cartilage, coupled with the poor intrinsic healing capacity of this avascular connective tissue, there is a great demand for an articular cartilage substitute. As the bearing material of diarthrodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue-engineered constructs. We have previously demonstrated that by using a functional tissue engineering approach that incorporates mechanical loading into the long-term culture environment, one can enhance the development of mechanical properties in chondrocyte-seeded agarose constructs. As these gel constructs begin to achieve material properties similar to that of the native tissue, however, new challenges arise, including integration of the construct with the underlying native bone. To address this issue, we have developed a technique for producing gel constructs integrated into an underlying bony substrate. These osteochondral constructs develop cartilage-like extracellular matrix and material properties over time in free swelling culture. In this study, as a preliminary to loading such osteochondral constructs, finite element modeling (FEM) was used to predict the spatial and temporal stress, strain, and fluid flow fields within constructs subjected to dynamic deformational loading. The results of these models suggest that while chondral ("gel alone") constructs see a largely homogenous field of mechanical signals, osteochondral ("gel bone") constructs see a largely inhomogeneous distribution of mechanical signals. Such inhomogeneity in the mechanical environment may aid in the development of inhomogeneity in the engineered osteochondral constructs. Together with experimental observations, we anticipate that such modeling efforts will provide direction for our efforts aimed at the optimization of applied physical forces for the functional tissue engineering of an osteochondral articular cartilage substitute.     

Extracellular Vesicles in chondrogenesis and Cartilage regeneration

Extracellular vesicles (EVs), mainly exosomes and microvesicles, are bilayer lipids containing biologically active information, including nucleic acids and proteins. They are involved in cell communication and signalling, mediating many biological functions including cell growth, migration and proliferation. Recently, EVs have received great attention in the field of tissue engineering and regenerative medicine. Many in vivo and in vitro studies have attempted to evaluate the chondrogenesis potential of these microstructures and their roles in cartilage regeneration. EVs derived from mesenchymal stem cells (MSCs) or chondrocytes have been found to induce chondrocyte proliferation and chondrogenic differentiation of stem cells in vitro. Preclinical studies have shown that exosomes derived from MSCs have promising results in cartilage repair and in cell-free therapy of osteoarthritis. This review will focus on the in vitro and in vivo chondrogenesis and cartilage regeneration of EVs as well as their potential in the treatment of osteoarthritis.     

Advances in 3D printing of composite scaffolds for the repairment of bone tissue associated defects

The conventional methods of using autografts and allografts for repairing defects in bone, the osteochondral bone, and the cartilage tissue have many disadvantages, like donor site morbidity and shortage of donors. Moreover, only 30% of the implanted grafts are shown to be successful in treating the defects. Hence, exploring alternative techniques such as tissue engineering to treat bone tissue associated defects is promising as it eliminates the above-mentioned limitations. To enhance the mechanical and biological properties of the tissue engineered product, it is essential to fabricate the scaffold used in tissue engineering by the combination of various biomaterials. Three-dimensional (3D) printing, with its ability to print composite materials and with complex geometry seems to have a huge potential in scaffold fabrication technique for engineering bone associated tissues. This review summarizes the recent applications and future perspectives of 3D printing technologies in the fabrication of composite scaffolds used in bone, osteochondral, and cartilage tissue engineering. Key developments in the field of 3D printing technologies involves the incorporation of various biomaterials and cells in printing composite scaffolds mimicking physiologically relevant complex geometry and gradient porosity. Much recently, the emerging trend of printing smart scaffolds which can respond to external stimulus such as temperature, pH and magnetic field, known as 4D printing is gaining immense popularity and can be considered as the future of 3D printing applications in the field of tissue engineering.     

Composite scaffolds for cartilage tissue engineering

Tissue engineering remains a promising therapeutic strategy for the repair or regeneration of diseased or damaged tissues. Previous approaches have typically focused on combining cells and bioactive molecules (e.g., growth factors, cytokines and DNA fragments) with a biomaterial scaffold that functions as a template to control the geometry of the newly formed tissue, while facilitating the attachment, proliferation, and differentiation of embedded cells. Biomaterial scaffolds also play a crucial role in determining the functional properties of engineered tissues, including biomechanical characteristics such as inhomogeneity, anisotropy, nonlinearity or viscoelasticity. While single-phase, homogeneous materials have been used extensively to create numerous types of tissue constructs, there continue to be significant challenges in the development of scaffolds that can provide the functional properties of load-bearing tissues such as articular cartilage. In an attempt to create more complex scaffolds that promote the regeneration of functional engineered tissues, composite scaffolds comprising two or more distinct materials have been developed. This paper reviews various studies on the development and testing of composite scaffolds for the tissue engineering of articular cartilage, using techniques such as embedded fibers and textiles for reinforcement, embedded solid structures, multi-layered designs, or three-dimensionally woven composite materials. In many cases, the use of composite scaffolds can provide unique biomechanical and biological properties for the development of functional tissue engineering scaffolds.     

Gene transfer strategies in tissue engineering

Aiming for regeneration of severed or lost parts of the body, the combined application of gene therapy and tissue engineering has received much attention by regenerative medicine. Techniques of molecular biology can enhance the regenerative potential of a biomaterial by co-delivery of therapeutic genes, and several different strategies have been used to achieve that goal. Possibilities for application are many-fold and have been investigated to regenerate tissues such as skin, cartilage, bone, nerve, liver, pancreas and blood vessels. This review discusses advantages and problems encountered with the different gene delivery strategies as far as they relate to tissue engineering, analyses the positive aspects of polymeric gene delivery from matrices and discusses advances and future challenges of gene transfer strategies in selected tissues.     

Phenotypic analysis of bovine chondrocytes cultured in 3D collagen sponges: effect of serum substitutes

Repair of damaged cartilage usually requires replacement tissue or substitute material. Tissue engineering is a promising means to produce replacement cartilage from autologous or allogeneic cell sources. Scaffolds provide a three-dimensional (3D) structure that is essential for chondrocyte function and synthesis of cartilage-specific matrix proteins (collagen type II, aggrecan) and sulfated proteoglycans. In this study, we assessed porous, 3D collagen sponges for in vitro engineering of cartilage in both standard and serum-free culture conditions. Bovine articular chondrocytes (bACs) cultured in 3D sponges accumulated and maintained cartilage matrix over 4 weeks, as assessed by quantitative measures of matrix content, synthesis, and gene expression. Chondrogenesis by bACs cultured with Nutridoma as a serum replacement was equivalent or better than control cultures in serum. In contrast, chondrogenesis in insulin-transferrin-selenium (ITS⁺³) serum replacement cultures was poor, apparently due to decreased cell survival. These data indicate that porous 3D collagen sponges maintain chondrocyte viability, shape, and synthetic activity by providing an environment favorable for high-density chondrogenesis. With quantitative assays for cartilage-specific gene expression and biochemical measures of chondrogenesis in these studies, we conclude that the collagen sponges have potential as a scaffold for cartilage tissue engineering.     

生物支架材料——组织工程连载之二

具有三维结构的支架材料是组织工程的核心内容之一。现有组织工程支架可分为天然生物材料、合成有机材料和无机材料三类。支架材料近年来研究十分活跃,不仅在组织工程的最早产品人工皮肤领域进行了更为完善的研究和开发,同时在诸如人工骨、软骨、神经、血管、皮肤、肝、脾、肾、膀胱等方面进行了大量研究和探索。与普通组织工程支架需要预先制备并在体外成型不同,近年来在骨和软骨组织工程实践中兴起的可注射支架具有许多优势,是未来组织工程支架发展的重要方向之一。     

Low intensity ultrasound as a supporter of cartilage regeneration and its engineering

Ultrasound (US) is being used widely in clinic for diagnostic and therapeutic purposes, but clinical utilization of low intensity ultrasound (LIUS) has been very limited. However, therapeutic potential of LIUS has been reported in animal models of musculoskeletal system disorders, and its application is being expanded in various fields. This review will focus on the application of LIUS on the cartilage tissue engineering and repair of cartilage disorder such as osteoarthritis (OA). We will introduce our experimental results showing the LIUS effects on the chondrocyte viability, proliferation and matrix protein synthesisin vitro, and its application in the cartilage tissue engineering using mesenchymal stem cells (MSCs)in vivo. Also the current status on the issues will be discussed by comparing our results with those of other laboratories. In conclusion, we suggest that LIUS is an efficient and clinically applicable method for cartilage tissue engineering and cartilage repair.     

Lumican inhibits collagen deposition in tissue engineered cartilage

Lumican is a glycoprotein that is found in the extracellular matrix of many connective tissues, including cartilage. It is a member of the small leucine-rich repeat proteoglycans family and along with two others, decorin and fibromodulin, has the capacity to bind to fibrillar collagens and limit their growth. Cartilage tissue engineering provides a potential method for the production of three-dimensional tissue for implantation into eroded joints. Many studies have demonstrated the growth of cartilage in vitro. However in all cases, biochemical analysis of the tissue revealed a significant deficit in the collagen content. We have now tested the hypothesis that the reduced collagen accumulation in engineered cartilage is a result of over-expression of decorin, fibromodulin or lumican. We have found that the lumican gene and protein are both over-expressed in engineered compared to natural cartilage whereas this is not the case for decorin or fibromodulin. Using a small hairpin lumican antisense sequence we were able to knockdown the lumican gene and protein expression in chondrocytes being used for tissue engineering. This resulted in increased accumulation of type II collagen (the major collagen of cartilage) whilst there was no significant alteration in the proteoglycan content. Furthermore, the antisense knockdown of lumican resulted in an increase in the average collagen fibril diameter measured by transmission electron microscopy. These results suggest that lumican plays a pivotal role in the development of tissue engineered cartilage and that regulation of this protein may be important for the production of high-quality implants.     

Evaluation of rabbit auricular chondrocyte isolation and growth parameters in cell culture

Auricular cartilage is an attractive potential source of cells for many tissue engineering applications. However, there are several requirements that have to be fulfilled in order to develop a suitable tissue engineered implant. Animal experiments serve as important tools for validating novel concepts of cartilage regeneration; therefore rabbit auricular chondrocytes were studied. Various parameters including isolation procedures, passage number, rate of proliferation and gene expression profile for major extracellular matrix components were evaluated in order to assess the potential use of elastic chondrocytes for tissue engineering. Chondrocytes were isolated from rabbit ear cartilage and grown in monolayer cultures over four passages. Yields of harvested cells and proliferation were analysed from the digestion step to the fourth passage, and changes in phenotype were monitored. The proliferation capacity of cell cultures decreased during cultivation and was accompanied by enlargement of cells, this phenomenon being especially evident in the third and fourth passages. The expression of cartilage specific genes for collagen type II, aggrecan and cartilage non-specific collagen type I was determined. The mRNA levels for all three genes were obviously lower in the primo culture than immediately after isolation. During subsequent cultivation the expression of collagen type II decreased further, while there were only slight changes in expression of aggrecan and collagen type I. This study provides a valuable basis for testing of different tissue engineering applications in rabbit model, where auricular chondrocytes are considered as cell source.     

Orthopedic gene therapy—lost in translation?

Orthopedic gene therapy has been the topic of considerable research for two decades. The preclinical data are impressive and many orthopedic conditions are well suited to genetic therapies. But there have been few clinical trials and no FDA-approved product exists. This paper examines why this is so. The reasons are multifactorial. Clinical translation is expensive and difficult to fund by traditional academic routes. Because gene therapy is viewed as unsafe and risky, it does not attract major funding from the pharmaceutical industry. Start-up companies are burdened by the complex intellectual property environment and difficulties in dealing with the technology transfer offices of major universities. Successful translation requires close interactions between scientists, clinicians and experts in regulatory and compliance issues. It is difficult to create such a favorable translational environment. Other promising fields of biological therapy have contemplated similar frustrations approximately 20 years after their founding, so there seem to be more general constraints on translation that are difficult to define. Gene therapy has noted some major clinical successes in recent years, and a sense of optimism is returning to the field. We hope that orthopedic applications will benefit collaterally from this upswing and move expeditiously into advanced clinical trials.     

Tendon tissue engineering: progress, challenges, and translation to the clinic

The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products.     

微载体技术在软骨损伤修复中的应用与展望北大核心CSCD

软骨内部无血管结构、细胞外基质含量高的特点,使软骨组织的自我恢复能力很差。在临床治疗中,轻度的软骨缺损通常采用物理治疗或药物治疗方式,严重者需进行手术治疗。近年来,软骨组织工程技术为治疗软骨缺损提供了新的思路,与传统的手术治疗方式相比,结合软骨组织工程技术进行治疗具有创口小、恢复佳的优点。将微载体技术融入组织工程支架的设计中,可以利用微载体直径小、能够负载多种生长因子的特点,进一步扩展支架功能、促进软骨组织再生。文中首先对微载体技术进行介绍,对近年来微载体的主要制备方式和创新内容进行了概括总结,作为后续介绍的基础内容。然后对应用于软骨修复中的微载体进行了材料和功能上的划分,介绍了不同材料、不同功能微载体的属性特征和在软骨修复方面的具体应用,最后结合该领域发展历程对其今后发展趋势及方向进行展望,并基于笔者团队关于骨软骨一体化层状支架的研究,提出了通过微载体优化层状支架性能的思路,有望制备出更贴合天然软骨结构特征的仿生支架。