Directionally solidified biopolymer scaffolds: Mechanical properties and endothelial cell responses

Vascularization is a primary challenge in tissue engineering. To achieve it in a tissue scaffold, an environment with the appropriate structural, mechanical, and biochemical cues must be provided enabling endothelial cells to direct blood vessel growth. While biochemical stimuli such as growth factors can be added through the scaffold material, the culture medium, or both, a well-designed tissue engineering scaffold is required to provide the necessary local structural and mechanical cues. As chitosan is a well-known carrier for biochemical stimuli, the focus of this study was on structure-property correlations, to evaluate the effects of composition and processing conditions on the three-dimensional architecture and properties of freeze-cast scaffolds; to establish whether freeze-east scaffolds are promising candidates as constructs promoting vascularization; and to conduct initial tissue culture studies with endothelial cells on flat substrates of identical compositions as those of the scaffolds to test whether these are biocompatible and promote cell attachment and proliferation.     

石墨烯基涂层的性质及在抗菌和组织工程中的应用

石墨烯材料--石墨烯纳米片(Graphene nanoflakes,GFs)、氧化石墨烯(GO)或还原氧化石墨烯(rGO)、化学气相沉积技术制备的石墨烯膜(CVD-G),自问世起,迅速成为社会各界广泛关注的新型碳纳米材料。通过转移方法或者溶剂助技术,可以将CVD-G和表面含有亲水基团的GFs或GO涂覆于基体表面,形成石墨烯基涂层,涂层以其独特的形貌、结构、物理化学性质,呈现出良好的抗菌活性和细胞外基质特点,显著影响细胞的粘附、增殖和分化等行为。经过近十年的研究,生物活性石墨烯基涂层材料在细胞培养、细胞生长、组织工程支架和生物医疗器械中展示出巨大的应用潜力。着重围绕石墨烯涂层的成分和制备方法,总结具有抗菌活性的石墨烯材料所取得的重要成果与最新进展,围绕石墨烯基二维涂层(涂覆于基底的二维表面)和石墨烯基三维结构(基底为三维支架)对多种哺乳细胞的相容性和细胞行为调控,综述了石墨烯材料在组织工程支架和植入体表面改性中的研究进展,提出了生物活性石墨烯基涂层的研制方向与应用展望等。     

Three-dimensional chitosan-nanohydroxyapatite composite scaffolds for bone tissue engineering

We describe the structure of biodegradable chitosan-nanohydroxyapatite (nHA) composites scaffolds and their interaction with pre-osteoblasts for bone tissue engineering. The scaffolds were fabricated via freezing and lyophilization. The nanocomposite scaffolds were characterized by a highly porous structure and pore size of ∼50–125 μm, irrespective of nHA content. The observed significant enhancement in the biological response of pre-osteoblast on nanocomposite scaffolds expressed in terms of cell attachment, proliferation, and widespread morphology in relation to pure chitosan points toward their potential use as scaffold material for bone regeneration.     

新型多孔镁压缩性能的有限元分析

利用有限元方法建立了激光打孔制备的直孔型多孔镁样品的压缩模型,系统分析了孔隙率、孔径及孔的排布对多孔镁样品压缩性能的影响,初步探讨了多孔镁在压缩过程中的变形规律.模拟计算结果表明,随着孔隙率、孔径的增加和孔的排布角的减小,多孔镁压缩曲线下移,屈服强度和弹性模量随之下降;多孔镁的压缩变形规律符合金属的最小阻力定律.     

不同类型多孔结构生物材料支架制备及其性能优化

多孔支架是组织工程应用中的关键环节,类似细胞外基质的作用,支撑细胞的粘附和随后细胞向组织的衍化。虽然目前已采用多种制备技术研发出大量的多孔支架,但是多孔生物材料支架的制备和性能优化,仍然是组织工程支架领域的研究热点。结合实验室工作,综述了多种制备不同类型多孔结构生物材料支架的制备技术,主要包括颗粒和纤维堆积型支架、泡沫浸渍法支架和颗粒制孔支架等的制备技术,并阐述了这些制备技术对多孔结构支架的孔结构、贯通性和力学性能的改善效果。其目的旨在提供满足组织工程需求的多孔生物材料支架。     

Fabrication of Bioceramic Bone Scaffolds for Tissue Engineering

In this study, microhydroxyapatite and nanosilica sol were used as the raw materials for fabrication of bioceramic bone scaffold using selective laser sintering technology in a self-developed 3D Printing apparatus. When the fluidity of ceramic slurry is matched with suitable laser processing parameters, a controlled pore size of porous bone scaffold can be fabricated under a lower laser energy. Results shown that the fabricated scaffolds have a bending strength of 14.1 MPa, a compressive strength of 24 MPa, a surface roughness of 725 nm, a pore size of 750 μm, an apparent porosity of 32%, and a optical density of 1.8. Results indicate that the mechanical strength of the scaffold can be improved after heat treatment at 1200 °C for 2 h, while simultaneously increasing surface roughness conducive to osteoprogenitor cell adhesion. MTT method and SEM observations confirmed that bone scaffolds fabricated under the optimal manufacturing process possess suitable biocompatibility and mechanical properties, allowing smooth adhesion and proliferation of osteoblast-like cells. Therefore, they have great potential for development in the field of tissue engineering.     

Ion-beam irradiation into biodegradable nanofibers for tissue engineering scaffolds

Tissue engineering scaffolds require cell affinity, biodegradability, and desirable mechanical properties. Poly-_L-lactic acid (PLLA) has been investigated for tissue engineering scaffolds owing to its biodegradability and mechanical strength. Electrospun fibers have large surface area and the fibrous structure provides necessary properties for cell attachment, proliferation, differentiation, and sufficient stiffness. PLLA fibers were irradiated with Kr⁺ at an energy of 50 keV with fluences of 1 × 10¹³, 1 × 10¹⁴, and 1 × 10¹⁵ ions/cm² to improve cell affinity. Morphological change was observed by scanning electron microscopy (SEM). Surface properties were measured by FT-IR-ATR and Raman spectroscopy. L929 cell attachment to Kr⁺-irradiated fibers was evaluated. After the irradiation, the average fiber diameter decreased with high fluence. From the results of the surface analyses, the original chemical bonds were broken and new carbon structures were induced. L929 cell attachment was dramatically improved compared with non-irradiated fibers. Thus, ion-beam irradiated fibers are suitable for tissue engineering scaffolds. This technique is expected to be useful in repairing defects, such as those in nerve, vascular, and liver, in regenerative medicine.     

Fabrication and Characterization of Nanopillar-Like HA Coating on Porous Ti6Al4V Scaffold by a Combination of Alkali–Acid-Heat and Hydrothermal Treatments

Porous titanium scaffold with suitable porous architecture exhibits enormous potentials for bone defect repairs. However,insufficient osteointegration and osteoinduction still remain to open as one of the major problems to achieve satisfactory therapeutic effect. To solve this problem, many studies have been carried out to improve the bioactivity of porous titanium scaff old by surface modifications. In this study, porous Ti6Al4V scaff olds were fabricated using additive manufacturing technique. Porous architectures were built up based on a diamond pore structure unit. Alkali–acid-heat(AH) treatment was applied to create a TiO_2 layer on the porous Ti6Al4V scaff old(AH-porous Ti6Al4V). Subsequently, a hydrothermal treatment was employed to enable the formation of HA coating with nanopillar-like morphology on the alkali–acid-heat-treated surface(HT/AH-porous Ti6Al4V). The effects of surface modifications on apatite-forming ability, protein adsorption,cell attachment, cell proliferation and osteogenic gene expression were studied using apatite-forming ability test, protein adsorption assay and in vitro cell culture assay. It was found that the HT/AH-porous Ti6Al4V exhibited the highest apatite formation ability and best affinity to fibronectin and vitronectin. In vitro studies indicated that the mesenchymal stem cells(MSCs) cultured on the HT/AH-porous Ti6Al4V presented improved adhesion and differentiation compared with the porous Ti6Al4V and AH-porous Ti6Al4V.     

Novel fabrication of forsterite scaffold with improved mechanical properties

In this study, the macroporous forsterite scaffolds with highly interconnected spherical pores, with sizes ranged from 50 to 200 μm have been successfully fabricated via gelcasting method. The crystallite size of the forsterite scaffolds was measured in the range 26-35 nm. Total porosity of different bodies sintered at different sintering temperatures was calculated in the range 81-86%, while open porosity ranges from 69 to 78%. The maximum values of compressive strength and elastic modulus of the prepared scaffolds were found to be about 2.43 MPa and 182 MPa, respectively, which are close to the lower limit of the compressive strength and elastic modulus of cancellous bone and the compressive strength is equal to the standard for a porous bioceramic bone implant (2.4 MPa). Transmission electron microscopy analyses showed that the particle sizes are smaller than 100 nm. In vitro test in the simulated body fluid proved the good bioactivity of the prepared scaffold. It seems that, the mentioned properties could make the forsterite scaffold appropriate for tissue engineering applications, but cell culture and in vivo tests are needed for more confidence.     

Bioactive Ca-P scaffolds used for bone reconstruction

1　INTRODUCTIONSkeletalreconstructionorregenerationisre quiredincasesinvolvinglargedefectscreatedbytu morresection ,trauma ,andskeletalabnormalities .Graftsandflapsofautogenoustissuearetwoofthemostsuccessfulmeansofreconstructionbecausetheyallowthetransplantationofbonecontainingbioactivemolecules,livecells ,andfrequently ,avascularsup plythatallowthetransplanttosurviveandremodeleveninhostileradiatedenvironments .However ,onlyaminimalamountoftissuecanbeharvestedforauto grafts,anditisverydiff…     

多孔钛骨组织工程支架设计及孔结构表征

针对目前骨组织工程支架微孔结构难以准确设计制备的问题,提出了一种基于点云的参数化建模+3D打印新方法。通过提取cube(C)、diamond(D)、gyroid(G)3种结构的型面函数点云数据,完成对不同孔结构特征的参数化建模。通过对模型有限元力学分析,对不同孔结构特征的多孔钛骨组织支架进行力学设计与订制。借助激光选区熔融(SLM)3D打印技术,完成对不同孔特征的骨组织支架快速成型。对多孔钛骨组织支架进行了相关材料学表征,包括孔结构表征与力学性能测试。结果表明:参数化模型的快速成型制造,能够有效地设计制备钛合金骨组织工程支架的孔结构特性,且可有效设计订制支架的力学性能,从仿生的角度实现多孔钛合金骨组织工程支架生物学功能的设计优化。     

Laser process effects on physical texture and wetting in implantable Ti-alloys

Wetting is an important aspect for implantable biomaterials, as it affects the initial interaction with physiological fluids, which in turn dictates the protein adsorption, cell attachment, and tissue integration at the interface. In light of this in the present overview, surface engineering techniques based on laser processing of implantable titanium alloys for improved wettability and cell compatibility is discussed. Here three different laser processing techniques, laser interference patterning, continuous wave laser direct melting, and pulsed laser direct melting and the influence of each type of processing on the micro-texture evolution are studied Finally, the effect of micro-textures on the wettability and thereby its in vitro bioactivity and in vitro biocompatibility is systematically discussed.     

无机-有机复合组织器官工程材料的微纳制造

无机-有机复合组织器官工程支架的微纳制造是近年来兴起的生物材料研究领域,相对传统的生物材料与组织工程材料制造技术,微纳制造整合了微纳米技术、计算机辅助设计、数字化制造等先进技术手段,为新型生物医用材料的开发以及生物材料制造新技术、新设备的研发提供了新的技术路线。综述了生物医用材料、特别是组织器官工程与组织修复材料微纳制造技术现状及发展趋势,主要内容包括生物材料的微纳米化及实现途径、组织器官工程支架材料的数字化设计、组织器官工程支架材料的数字化制造新技术等,对我国组织器官工程（修复）材料数字化微纳制造新技术的优先发展领域提出了展望。     

组织工程骨支架内部微流体流场研究进展

组织工程支架的结构、空间走向、孔隙率是制约组织工程学发展的重要因素,支架内微流体流场直接影响着细胞的吸附、增殖、分化和流-固耦合引起的支架应力应变,且支架内微流体流场各种因素交互作用复杂,作用机制尚未明确,对其内部微管孔中的微流体流动特性的研究尚处于起步阶段。通过对组织工程支架内部流场及流体剪应力和新组织相互影响的研究情况进行阐述,发现在使用数值方法进行模拟仿真的同时,还缺少相应的物理实验验证,而快速成型技术和新材料的发展,对搭建微流体实验平台,探索骨支架及内部微流体流场的优化具有一定的工程意义。     

Surface modification of PLGA/β-TCP scaffold for bone tissue engineering: Hybridization with collagen and apatite

The objective of this experiment is to produce a novel scaffold composed of poly (lactic-co-glycolic acid) (PLGA)/β-tricalciumphosphate (β-TCP) skeleton covered with apatite/collagen sponge. BMSCs were used to evaluate the cell behavior on the hybrid scaffold. Cell morphology on the surfaces of PLGA/β-TCP skeleton and PLGA/β-TCP skeleton with apatite/collagen sponge composite coating was studied by scanning electron microscopy (SEM). Cell proliferation was assessed by cell number counting. Differentiated BMSCs function was monitored by measuring alkaline phosphates activity of the cells. These results demonstrated that the apatite/collagen sponge composite coating could improve cell proliferation and ALP activity of the hybrid scaffolds and increase its hydrophilicity after hybridization. The experiment suggested that the PLGA/β-TCP skeleton with apatite/collagen sponge composite coating is promising as a candidate 3D substrate for bone tissue engineering.     

Understanding biomanufacturing of soy-based scaffolds for cell-cultured meat by vat polymerization

Emerging cell-cultured meat uses advances in stem cell biology and tissue engineering to manufacture animal-derived food from culturing. To achieve complex textures in cell-cultured meat, bioprinted soy-based polymers are proposed as a photosensitive edible scaffold material. Understanding the properties of these scaffolds across critical product development stages (i.e., cooking and consumption) is important in design for manufacturing. The results demonstrated that the thermomechanical and -chemical properties were not affected by high-temperature exposure associated with cooking. This research provides a foundation for high-temperature edible mechanics in photolithographic manufacturing of cell-cultured meat and establishes a new design space for tunable food properties.     

Three-Dimensional Quantification of Calcium Salt-Composite Resorption (CSC) In Vitro by Micro-computed Tomography (Micro-CT)

The commonly applied cell-based, two-dimensional (2D) in vitro resorption assays for biomaterials are limited in a variety of cases, including high initial roughness of material surface, uncontrollable solubilization (or resorption) of the entire material surface, or complex three-dimensional (3D) structure of the bioactive material itself. All these make the accurate assessment and successful selection of the optimal bone substitute material difficult. In vivo, micro-computed tomography (micro-CT) has been widely applied for the analysis of bone physiology and pathology, as well as for the 3D analysis of scaffolds for bone tissue engineering. In this study, we show that micro-CT can also be applied for the in vitro analysis of osteoclast-mediated resorption of biomaterials. For our experiments, we chose a calcium salt-composite (composite of calcium sulphate (CSC), calcium carbonate, glycerin-1,2,3-tripalmiate), which evades common 2D in vitro resorption analysis as a result of its high surface roughness and material composition. Human osteoclasts were differentiated from precursor cells on the surface of the material for 28 days. Cells were analyzed for expression of tartrate-resistant acid phosphatase 5b (TRAP5b), multinuclearity, and size. Volumetric analysis of resorption was performed by micro-CT. Multinucleated osteoclasts developed on the surface of the material. TRAP5b expression of the cells on CSC was comparable with TRAP5b expression of cells cultivated on dentin for the first 3 weeks of culture. At day 28, TRAP5b expression, cell number, and size of the TRAP+ cells were reduced on the CSC when compared with cells on dentin. Volumetric anaylsis by micro-CT showed a strong cellular effect on resorption of CSC. We consider micro-CT to be a promising technique for 3D quantification of cell-based resorption that will allow the study of cellular resorption of materials in vitro, which were up to now confined to animal experimental analysis.     

A plasma-assisted bioextrusion system for tissue engineering

A challenge for tissue engineering is to produce synthetic scaffolds of adequate chemical, physical and biological cues effectively. This paper describes a plasma-assisted bio-extrusion system to produce functional-gradient scaffolds; it comprises pressure-assisted and screw-assisted extruders, and plasma jets. This paper also describes how the system conducts plasma surface modification during the polycaprolactone scaffold fabrication process. Water contact angle and in vitro biological tests confirm that the plasma modification alters the hydrophilicity properties of synthetic polymers and promotes proliferation of cells, leading to homogeneous cell colonization. The results suggest this system is promising for producing functional gradient scaffolds of biomaterials.     

钛合金变形Gyroid单元梯度多孔结构设计与分析

研究一种具有径向和轴向孔径梯度的变形Gyroid单元多孔结构参数化设计方法,采用激光选区熔化成形(selective laser melting, SLM)技术,制备出孔隙率为60%和75%的钛合金变形Gyroid单元梯度多孔结构样件。使用有限元法(finiteelementmethod,FEM)对4组梯度多孔支架模型及2组均质模型进行静力学仿真分析,对制备的钛合金梯度多孔样件进行力学性能测试,并与已测试过的均质样件进行力学性能对比分析。有限元计算结果与力学性能试验结果共同表明：变形Gyroid单元多孔结构力学性能随孔隙率的升高而降低,孔隙率相同时,径向梯度多孔支架力学性能优于均质多孔支架,更适用于皮质骨的骨缺损修复,轴向梯度多孔支架力学性能相比均质多孔支架有所减弱,更适用于松质骨。     

TiO<Subscript>2</Subscript> nanotube structures for enhanced cell and biological functionality

Nanostructures have pronounced effects on biological processes such as growth of cells and their functionality. Advances in biomaterial surface structure and design have resulted in improved tissue engineering. Nanotechnology can be utilized for optimization of titanium implants with a formation of vertically aligned TiO₂ nanotube arrays on the implant surface. The anodic oxidation of the titanium implant surface to form a TiO₂ nanotube array involves electrochemical processes and self assembly. In this paper, the mechanism of nanotube formation, nanotube bio-characteristics, and their emerging role in soft and hard tissue engineering as well as in regenerative medicine will be reviewed, and the beneficial effects of surface nanotubes on cell adhesion, proliferation, and functionality will be discussed in relation to potential orthopedics applications.