组织工程支架的最新研究

综述了最近几年国内外组织工程支架的研究状况，重点介绍了组织工程支架的制备技术（包括浇铸／沥滤致孔、低热高压、分相、超临界CO2、静电纺丝等），选用材料以及在皮肤、软骨、骨和心血管等组织修复中应用的最新进展。     

组织工程用海藻酸盐水凝胶的研究进展

海藻酸钠已经被广泛应用于生物医学领域。本文从组织工程角度出发,综述了海藻酸盐水凝胶的形成机理、制备方法以及应用研究进展。     

Biofabrication of Sodium Alginate Hydrogel Scaffolds for Heart Valve Tissue Engineering

Every year, thousands of aortic valve replacements must take place due to valve diseases. Tissue-engineered heart valves represent promising valve substitutes with remodeling, regeneration, and growth capabilities. However, the accurate reproduction of the complex three-dimensional (3D) anatomy of the aortic valve remains a challenge for current biofabrication methods. We present a novel technique for rapid fabrication of native-like tricuspid aortic valve scaffolds made of an alginate-based hydrogel. Using this technique, a sodium alginate hydrogel formulation is injected into a mold produced using a custom-made sugar glass 3D printer. The mold is then dissolved using a custom-made dissolving module, revealing the aortic valve scaffold. To assess the reproducibility of the technique, three scaffolds were thoroughly compared. CT (computed tomography) scans showed that the scaffolds respect the complex native geometry with minimal variations. The scaffolds were then tested in a cardiac bioreactor specially designed to reproduce physiological flow and pressure (aortic and ventricular) conditions. The flow and pressure profiles were similar to the physiological ones for the three valve scaffolds, with small variabilities. These early results establish the functional repeatability of this new biofabrication method and suggest its application for rapid fabrication of ready-to-use cell-seeded sodium alginate scaffolds for heart valve tissue engineering.     

皮肤组织工程支架材料的研究进展

综述了近年来国内外关于皮肤支架材料的研究现状,重点介绍天然皮肤支架材料中的胶原、壳聚糖和明胶类皮肤支架以及人工合成皮肤支架材料的研究进展。     

Fabrication of Gentamicin Sulfate-Loaded 3D-Printed Polyvinyl Alcohol/Sodium Alginate/Gelatin-Methacryloyl Hybrid Scaffolds for Skin Tissue Replacement

3D-printed scaffolds can better mimic the function of human skin, both biologically and mechanically. Within the scope of this study, the effect of the addition of different amounts (10, 15, 20 mg) of gentamicin sulfate (GS) to a 10 mL solution of natural and synthetic polymers is investigated. Sodium alginate (SA), gelatin-methacryloyl (GelMA), and polyvinyl alcohol (PVA) are chosen as bioactive materials. The surface morphology and pore structures are visualized by scanning electron microscopy (SEM). According to the results, it is observed that the pore sizes of all scaffolds are smaller than 270 µm, the lowest value (130 µm) is obtained in the scaffold loaded with 15 mg GS, and it also has the highest tensile strength value (12.5 ± 7.6 MPa). Similarly, it is observed that the tensile strength (9.7 ± 4.5 MPa) is high in scaffold loaded with 20 mg GS. The biocompatibility test is performed with fibroblast cells, and the results show that the scaffolds are biocompatible with cells. The antibacterial test is carried out against the S.aureous and E. coli and the results indicate that all GS-loaded scaffolds demonstrate antibacterial activity.     

Piezoelectric Electrospun Fibrous Scaffolds for Bone,Articular Cartilage and Osteochondral Tissue Engineering

Osteochondral tissue (OCT) related diseases, particularly osteoarthritis, number among the most prevalent in the adult population worldwide. However, no satisfactory clinical treatments have been developed to date to resolve this unmet medical issue. Osteochondral tissue engineering (OCTE) strategies involving the fabrication of OCT-mimicking scaffold structures capable of replacing damaged tissue and promoting its regeneration are currently under development. While the piezoelectric properties of the OCT have been extensively reported in different studies, they keep being neglected in the design of novel OCT scaffolds, which focus primarily on the tissue’s structural and mechanical properties. Given the promising potential of piezoelectric electrospun scaffolds capable of both recapitulating the piezoelectric nature of the tissue’s fibrous ECM and of providing a platform for electrical and mechanical stimulation to promote the regeneration of damaged OCT, the present review aims to examine the current state of the art of these electroactive smart scaffolds in OCTE strategies. A summary of the piezoelectric properties of the different regions of the OCT and an overview of the main piezoelectric biomaterials applied in OCTE applications are presented. Some recent examples of piezoelectric electrospun scaffolds developed for potentially replacing damaged OCT as well as for the bone or articular cartilage segments of this interfacial tissue are summarized. Finally, the current challenges and future perspectives concerning the use of piezoelectric electrospun scaffolds in OCT regeneration are discussed.     

Decellularized Extracellular Matrix Scaffolds for Cardiovascular Tissue Engineering: Current Techniques and Challenges

Cardiovascular diseases are the leading cause of global mortality. Over the past two decades, researchers have tried to provide novel solutions for end-stage heart failure to address cardiac transplantation hurdles such as donor organ shortage, chronic rejection, and life-long immunosuppression. Cardiac decellularized extracellular matrix (dECM) has been widely explored as a promising approach in tissue-regenerative medicine because of its remarkable similarity to the original tissue. Optimized decellularization protocols combining physical, chemical, and enzymatic agents have been developed to obtain the perfect balance between cell removal, ECM composition, and function maintenance. However, proper assessment of decellularized tissue composition is still needed before clinical translation. Recellularizing the acellular scaffold with organ-specific cells and evaluating the extent of cardiomyocyte repopulation is also challenging. This review aims to discuss the existing literature on decellularized cardiac scaffolds, especially on the advantages and methods of preparation, pointing out areas for improvement. Finally, an overview of the state of research regarding the application of cardiac dECM and future challenges in bioengineering a human heart suitable for transplantation is provided.     

Development of Polyvinyl Alcohol Fibrous Biodegradable Scaffolds for Nerve Tissue Engineering Applications: In Vitro Study

In this study, polyvinyl alcohol (PVA) fibers were modified through an effective cross linking method. Adequate porosity and surface area are widely recognized as important parameters in the design of scaffolds for tissue engineering and therefore measurement of porosity is very important. Herein, porosity measurement of various surface layers of scaffold was done through a new method, and image analysis was used for this purpose. Scanning electron microscopy micrographs of nanofibrous scaffolds were converted to binary images using different thresholds and porosity of scaffold was measured in various layers. In addition, for ascertaining of cross linking of the PVA nanofibrous scaffolds, Fourier transform infrared spectroscopy analysis was employed. Also, the in vitro biodegradability of the nanofibrous scaffold was evaluated. The PVA crosslinked nanofibrous scaffold was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (PC12 cells). Finally, the results of the swelling behavior of the samples revealed that the cross linked PVA scaffold has a strong swelling about 450%.     

Carbon Dots-Mediated Fluorescent Scaffolds: Recent Trends in Image-Guided Tissue Engineering Applications

Regeneration of damaged tissues or organs is one of the significant challenges in tissue engineering and regenerative medicine. Many researchers have fabricated various scaffolds to accelerate the tissue regeneration process. However, most of the scaffolds are limited in clinical trials due to scaffold inconsistency, non-biodegradability, and lack of non-invasive techniques to monitor tissue regeneration after implantation. Recently, carbon dots (CDs) mediated fluorescent scaffolds are widely explored for the application of image-guided tissue engineering due to their controlled architecture, light-emitting ability, higher chemical and photostability, excellent biocompatibility, and biodegradability. In this review, we provide an overview of the recent advancement of CDs in terms of their different synthesis methods, tunable physicochemical, mechanical, and optical properties, and their application in tissue engineering. Finally, this review concludes the further research directions that can be explored to apply CDs in tissue engineering.     

Development and Characterization of Novel Biomimetic Composite Scaffolds Based on Bioglass‐Collagen‐Hyaluronic Acid‐Phosphatidylserine for Tissue Engineering Applications

Summary: Biomimetic scaffolds are appealing products for the repair of bone defects using tissue engineering strategies. The present study prepared novel biomimetic composite scaffolds with similar composite to natural bone using bioactive glass, collagen, hyaluronic acid, and phosphatidylserine. The microstructure, swelling ratio, biodegradability, and biomineralization characteristic of the composite scaffolds with and without hyaluronic acid and phosphatidylserine were compared and analyzed by SEM/EDAX, XRD, and FTIR techniques and in vitro test, and the properties can be influenced by 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC)/N‐hydroxysuccinimide (NHS) crosslinking. The optimized properties of the crosslinked composite scaffolds observed in this study show the possibility of their use of bioactive and bioresorbable scaffolds in bone tissue engineering.

SEM micrographs of BG‐COL‐HYA‐PS composite scaffolds after immersion in SBF for 1 d.     

骨组织工程支架材料

寻找理想的支架材料是目前骨组织工程研究的热点。本文阐述了用于骨组织丁程支架材抖的天然生物衍生材料、聚合物类材料、陶瓷材料及其复合材料等的研究现状,分析了这些材料的优缺点,并展望了骨组织工程支架材料的发展趋势。     

Oxidized Cashew Gum Scaffolds for Tissue Engineering

In the last few years, several strategies have been proposed to fabricate scaffolds for tissue engineering (TE) applications; however, they are based on harsh and time‐consuming techniques. The choice for natural polymers such as cashew gum (CG) allows to circumvent the demands of biocompatibility and degradability of TE systems. In this work, CG, a polysaccharide derived from Anacardium occidentale trees, is functionalized with aldehyde groups through periodate oxidation. The resultant oxidized cashew gum (CGO) is mixed with gelatin (GE) to yield a covalently crosslinked hydrogel. CGO/GE sponges are obtained by employing a freeze‐drying methodology to the previously obtained hydrogels. The mechanical properties, swelling ability, and porosity of the GE/CGO sponges are tuned by using CGO with different degrees of oxidation. The resultant sponges can maintain high levels of water absorption and recover their initial mechanical properties after cyclic compression. Moreover, these porous and mechanically robust devices can support the adhesion and proliferation of cells, which can envision their application for the regeneration of soft tissues.     

基于快速成型技术的组织工程支架制备进展

介绍了组织工程支架的重要性和基本要求,综述了组织工程支架制备中的新技术：三雏打印技术、熔融沉积模型以及选择性激光烧结等三种快速成型技术的基本原理及应用情况,指出了各种技术的特点并对其应用前景进行了展望。     

Fabrication of Polylactide‐Based Biodegradable Thermoset Scaffolds for Tissue Engineering Applications

The fabrication of tissue engineering scaffolds based on the polymerization of crosslinked polylactide using leaching and batch foaming to generate well‐controlled and interconnected biodegradable polymer scaffolds is reported. The scaffold fabrication parameters are studied in relation to the interpore connectivity, pore morphology, and structural stability of the crosslinked PLA scaffold. In vitro cell culture and in vitro degradation are used to analyze the biocompatibility and biodegradability of the scaffolds. The new crosslinked PLA thermoset scaffolds are highly suitable for bone tissue engineering applications due to their complex internal architecture, thermal stability, and biocompatibility.

     

Study of Different Delivery Modes of Chondroitin Sulfate Using Microspheres and Cryogel Scaffold for Application in Cartilage Tissue Engineering

This study focuses on the development of an efficient delivery modes designed for chondroitin sulfate (CS) for application in cartilage tissue engineering. Novel three-dimensional (3-D) scaffold fabricated from natural polymers such as chitosan and gelatin blended with chondroitin sulfate (CGC) were synthesized using cryogelation technology. Other methods to deliver CS were also tried, which included incorporation into microparticles for sustained release and embedding the CS loaded microparticles in CG (chitosan-gelatin) cryogel scaffold. Novel CGC scaffolds were characterized by rheology, scanning electron microscopy (SEM), and mechanical assay. Scaffolds exhibited compression modulus of 50 KPa confirming the utility of these scaffolds for cartilage tissue engineering. Primary goat chondrocytes were used for the in vitro testing of all the delivery modes. So this study shows that CS microparticles when given freely with matrix (chitosan–gelatin) or embedded into scaffold has potential to enhance chondrocyte proliferation together with improved matrix production than in control without microspheres.     

Polyhydroxybutyrate (PHB) Scaffolds as a Model for Nerve Tissue Engineering Application: Fabrication and In Vitro Assay

In this study, we fabricated PHB scaffolds by solid/liquid phase separation method. The properties of fabricated scaffolds were investigated using SEM, DMTA, and DSC. Our studies noticed that for an approach to scaffolds that contain tubular morphology and better mechanical properties, the solution should be frozen near crystallization temperature. For in vitro evaluation, the P19 mouse embryonal cell line was used as a model system. Results notice that cells attach and differentiate to the nerve cell. In vitro assay shows that it is a suitable model for use as a platform for neural tissue engineering applications.     

纤维素组织工程支架的研究进展

纤维素具有良好的生物相容性和可降解性,在生物组织工程领域作为支架材料的研究近年来受到研究者的关注。文章介绍了组织工程支架的性能要求,以及纤维素、细菌纤维素用于组织工程支架的研究现状。针对组织工程支架的分子设计、纳米化趋势,提出了纳米纤维素纤维用于组织工程支架的设想。并综述了纳米纤维素纤维制备的最新研究进展,预测了未来纤维素组织工程支架的发展趋势及前景。     

Novel Organic Solvent Free Micro-/Nano-fibrillar,Nanoporous Scaffolds for Tissue Engineering

Novel organic solvent free micro-/nano-fibrillar composite scaffolds have been manufactured using poly(L-lactide) and glycol-modified poly(ethylene terephthalate) to evaluate cell growth potential on the nanoporous networks. The authors describe a method for producing nanoporous scaffolds from polymer blends and highlights some limitations and inaccuracies when measuring mechanical properties of fibrillar porous structures. It illustrates the importance of determining the actual cross-sectional surface area of the load resisting fibers rather than using the simple geometrical area if properties are to be determined accurately. Cellular-biocompatible testing with a mouse pre-osteoblastic (early bone-forming cells) cell line shows promise, with a live monolayer of cells present on the biomaterial after 7–10 days of culture. In addition, scaffolds have also been manufactured by using the traditional electrospinning method and their cyto-biocompatibility compared to the micro-/nano-fibrillar composite scaffolds, employing cell attachment and morphology studies. Some scaffold manufacturing issues have also been identified and discussed in relation to improved cell growth.     

The Tunable Porous Structure of Gelatin–Bioglass Nanocomposite Scaffolds for Bone Tissue Engineering Applications: Physicochemical,Mechanical, and In Vitro Properties

Unidirectional freeze‐casting method is used to fabricate gelatin–bioglass nanoparticles (BGNPs) scaffolds. Transmission electron microscopy (TEM) images show that sol–gel prepared BGNPs are distributed throughout the scaffold with diameters of less than 10 nm. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetric are used to evaluate the physicochemical properties of BGNPs. Scanning electron microscopy (SEM) micrographs present an oriented porous structure and a homogeneous distribution of BGNPs in the gelatin matrix. The lamellar‐type structure indicates an improvement of mechanical strength and absorption capacity of the scaffolds. Increasing the concentration of BGNPs from 0 to 50 wt% have no noticeable effect on pore orientation, but decreases porosity and pore size distribution. Increase in BGNPs content improves the compressive strength. The absorption and biodegradation rate reduces with augmentation in BGNPs concentration. Bioactivity is evaluated through apatite formation after immersion of the nanocomposites in simulated body fluid and is verified by SEM–energy‐dispersive X‐ray spectroscopy (EDS), an element map analysis, X‐ray powder diffractometer, and FTIR spectrum. SEM images and methyl thiazolyl tetrazolium assay confirm the biocompatibility of scaffolds and the supportive behavior of nanocomposites in cellular spreading. The results show that gelatin–(30 wt%)bioglass nanocomposites have incipient physicochemical and biological properties.     

A Facile Strategy for Fabricating Tissue Engineering Scaffolds with Sophisticated Prevascularized Networks for Bulk Tissue Regeneration

Despite the fact that the field of tissue engineering has had considerable advances over the past two decades, a series of unsolved problems still remain. Vascularization is one of the most important factors that greatly influence the function and size of the engineered scaffolds, which limits the clinical applications. In this work, a facile extracted molding method is presented for fabricating bulk tissue scaffolds with spatial networks. Briefly, the branched templates are designed, coated with paraffin on the surface, immersed into the mixture of microbial transglutaminase and gelatin, and extracted from fully enzymatic cross‐linking gelatin. The perfusion test is done and the mechanical properties of the scaffolds are investigated. Furthermore, in vitro and in vivo experiments demonstrate the nontoxicity and biocompatibility of the materials and fabrication process. Thus, this approach has great potential to overcome the challenge of rapid oxygen and nutrient delivery to engineered vascularized tissues implanted in vivo, opening the way to clinical applications.