3D Printing of Cell-Container-Like Scaffolds for Multicell Tissue Engineering

The development of an engineered non-contact multicellular coculture model that can mimic the in vivo cell microenvironment of human tissues remains challenging. In this study, we successfully fabricated a cell-container-like scaffold composed of β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) bioceramic that contains four different pore structures, including triangles, squares, parallelograms, and rectangles, by means of three-dimensional (3D) printing technology. These scaffolds can be used to simultaneously culture four types of cells in a non-contact way. An engineered 3D coculture model composed of human bone-marrow-derived mesenchymal stem cells (HBMSCs), human umbilical vein endothelial cells (HUVECs), human umbilical vein smooth muscle cells (HUVSMCs), and human dermal fibroblasts (HDFs) with a spatially controlled distribution was constructed to investigate the individual or synergistic effects of these cells in osteogenesis and angiogenesis. The results showed that three or four kinds of cells cocultured in 3D cell containers exhibited a higher cell proliferation rate in comparison with that of a single cell type. Detailed studies into the cell–cell interactions between HBMSCs and HUVECs revealed that the 3D cell containers with four separate spatial structures enhanced the angiogenesis and osteogenesis of cells by amplifying the paracrine effect of the cocultured cells. Furthermore, the establishment of multicellular non-contact systems including three types of cells and four types of cells, respectively, cocultured in 3D cell containers demonstrated obvious advantages in enhancing osteogenic and angiogenic differentiation in comparison with monoculture modes and two-cell coculture modes. This study offers a new direction for developing a scaffold-based multicellular non-contact coculture system for tissue regeneration.     

3D打印HA微球支架的制备与表征

生物材料表面微结构对于成骨具有重要的影响,该研究以不同粒径(<60μm)的羟基磷灰石(HA)微球状粉体为原料,通过3D打印技术制备了一系列(HA0、HA10、HA30、HA50)生物陶瓷支架。不同支架具有相似的理化性能,由于微球粒径不同形成了不同的微结构,对其生物学性能造成不同的影响。相比传统非微球颗粒打印的支架(HA0), HA微球构成的支架能够提供更多细胞粘附和生长位点, 24 h的粘附实验显示HA30支架能显著促进骨髓间充质干细胞的伪足伸长;培养5 d的细胞增殖实验显示,微球支架上的细胞数量与HA0支架出现显著性差异,表面微球结构与细胞尺度相当的HA30支架具有最好的促增殖效果。因此,3D打印技术在可控制备HA支架宏观结构的同时,还可以通过控制生物陶瓷粉体的颗粒形貌,调控3D打印支架的表面微结构,从而优化其生物学效应,在骨组织工程领域具有良好的应用前景。     

三维打印羟基磷灰石晶须增强复合骨修复支架

利用三维打印技术成功制备羟基磷灰石晶须(HAPw)增强的聚己内酯(PCL)复合骨修复支架。通过改变三维打印的挤出速度和挤出气压, 使不同含量HAPw均能在PCL基材中一致排列并均匀分布。PCL支架的机械强度随HAPw含量增加显著提高, 添加33wt%HAPw使PCL支架强度提升了高达3倍。此外, HAPw使PCL支架表面与水的接触角从近100º降低至约50º, 有效改善了细胞表面粘附。经过体外人类骨髓间充质干细胞(hBMSC)在支架上的培养实验, 发现添加HAPw的复合支架具有更好的生物相容性, 能够有效促进hBMSC的增殖生长, 且HAPw-PCL复合支架上细胞具有更高的碱性磷酸酶(ALP)活性和OCN、RUNX2等相关成骨基因表达, 显示出hBMSCs向成骨方向更好的分化及成骨活性。     

3D Scaffolds to Study Basic Cell Biology

Mimicking the properties of the extracellular matrix is crucial for developing in vitro models of the physiological microenvironment of living cells. Among other techniques, 3D direct laser writing (DLW) has emerged as a promising technology for realizing tailored 3D scaffolds for cell biology studies. Here, results based on DLW addressing basic biological issues, e.g., cell‐force measurements and selective 3D cell spreading on functionalized structures are reviewed. Continuous future progress in DLW materials engineering and innovative approaches for scaffold fabrication will enable further applications of DLW in applied biomedical research and tissue engineering.     

PLGA组织工程支架材料在SBF中的降解性能和生物矿化性能

本文采用pH值测量、特性粘度、失重、DSC和电子探针的研究方法,研究了PLGA组织工程支架在模拟体液中的降解性能和生物矿化性能。研究发现随着在SBF中浸泡时间的增长,PLGA支架材料的分子量不断下降;浸泡在SBF中的PLGA组织工程支架材料的重量由沉积进程和降解进程共同决定;DSC测试显示,浸泡在SBF中的PLGA组织工程支架材料的羟基乙酸单元(GA)相对于乳酸单元(LA)更易降解;电子探针测试显示,浸泡在SBF中的PLGA组织工程支架材料表面有磷酸盐沉积物产生。     

复合材料梯度结构组织工程支架建模方法

使用传统方法制造组织工程细胞载体支架存在材料单一，结构简单的缺点，提出了一种基于快速成形技术（MEM工艺，类似于FDM）的复合材料梯度结构组织工程支架的建模方法，使用这种方法，可以按照支架的特点和要求，分别采用结构模板和材料模板进行支架的结构设计和材料设计，从而实现支架的多种材料和梯度结构。     

丝素/纳米纤维素晶须/壳聚糖多孔复合支架的应用

以冷冻干燥法制备多孔丝素(SF)支架,利用层层自组装将纳米纤维素晶须(CNW)和壳聚糖(CS)交替组装到多孔SF支架上得到SF/CNW-CS多孔复合支架。对SF/CNW-CS多孔复合支架的形貌和机械性能进行了表征。以MG-63细胞进行体外培养评估SF及SF/CNW-CS多孔复合支架的细胞相容性,MTT比色法和荧光图像的测试结果表明,与SF多孔支架相比,MG-63细胞在SF/CNW-CS多孔复合支架上的增殖、粘附和分化功能最高。因此,SF/CNW-CS支架有望成为骨组织工程的理想材料。     

Engineering 2D Mesoporous Silica@MXene‐Integrated 3D‐Printing Scaffolds for Combinatory Osteosarcoma Therapy and NO‐Augmented Bone Regeneration

The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb₂C MXene wrapped with S‐nitrosothiol (R? SNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.     

Glass,Ceramic, Polymeric,and Composite Scaffolds with Multiscale Porosity for Bone Tissue Engineering

Porosity affects performance of scaffolds for bone tissue engineering both in vitro and in vivo. Macropores (i.e., pores with a diameter >100 μm) are essential for cellular infiltration; micropores (i.e., pores with a diameter of 1–10 μm) promote cell adhesion and facilitate nutrient absorption. Scaffolds containing both macropores and micropores exploit the advantages of both pore sizes and have excellent osteogenic properties. Nanopores (i.e., pores with a diameter of 1–50 nm) can be included as well, to improve cell–material interactions by further enhancing the surface area of the scaffold. This article reviews fabrication techniques and properties of scaffolds with multiscale porosity, focusing on glass, ceramic, polymeric, and composite scaffolds. After discussing the structure of bone and how it inspired scaffolds for bone tissue engineering, pore nomenclature is introduced. Then, the techniques used to induce multiscale porosity, the nature of the pores created, and the effects of scaffold porosity on mechanical properties and biological activity of the scaffolds are discussed. The review concludes by providing an outlook for this field, including advancements that are made possible by computational modeling and artificial intelligence.     

Microfabricated Biomaterials for Engineering 3D Tissues

Mimicking natural tissue structure is crucial for engineered tissues with intended applications ranging from regenerative medicine to biorobotics. Native tissues are highly organized at the microscale, thus making these natural characteristics an integral part of creating effective biomimetic tissue structures. There exists a growing appreciation that the incorporation of similar highly organized microscale structures in tissue engineering may yield a remedy for problems ranging from vascularization to cell function control/determination. In this review, we highlight the recent progress in the field of microscale tissue engineering and discuss the use of various biomaterials for generating engineered tissue structures with microscale features. In particular, we will discuss the use of microscale approaches to engineer the architecture of scaffolds, generate artificial vasculature, and control cellular orientation and differentiation. In addition, the emergence of microfabricated tissue units and the modular assembly to emulate hierarchical tissues will be discussed.     

组织工程支架材料的研究进展

自19世纪以来,移植手术一直致力于修复由于创伤﹑感染﹑肿瘤所造成的大范围组织缺损,以恢复器官功能。自体移植是目前最常采用的疗法,但供体的有限性限制了其应用,而且会给患者带来很大的痛苦。组织工程的目标是通过种子细胞在三维支架材料上的黏附﹑生长进而修复受损的组织。三维支架是种子细胞形成组织之前赖以生存和依附的载体,能够正确引导新组织的生长。因此支架材料的选择就成了关键,本综述主要介绍目前应用于组织工程的生物支架材料的性能要求﹑发展现状以及发展前景。