不同浓度明胶水凝胶用于3D生物打印的初步研究

目的:利用天然高分子材料明胶的生物学性能及交联特性,构建不同浓度的可用于3D生物打印的生物墨水,并对其进行制备,表征与分析,为之后的生物打印提供材料基础.方法:基于以往研究,制备不同浓度的甲基丙烯酸酐(MA)改性明胶水凝胶,分别进行MA改性明胶水凝胶制备、溶胀性能、力学性能、营养液渗透、3D生物打印实验,以此来确定明胶...     

3D打印纳米纤维/藻酸盐基水凝胶的制备与表征

以2,2,6,6-四甲基哌啶氧化物(TEMPO)氧化细菌纤维素(TOBC)作为增强体,制备了一系列的纳米纤维/藻酸盐(SA)基纳米复合水凝胶,研究了TOBC对纳米复合水凝胶的微观形貌、压缩、溶胀、生物相容性等性能的影响。通过流变实验与3D打印实验探究TOBC/SA纳米复合水凝胶的可印刷能力。结果表明,TOBC的加入显著增强了SA水凝胶的压缩性能。当TOBC含量为50%时,水凝胶压缩强度可达260.9 kPa,压缩性能最优。TOBC增强了混合油墨的非牛顿性,并使触变恢复能力最高达到83%,可3D打印制造出结构可控的复杂结构。纳米复合水凝胶表现出优异的细胞相容性,在生物医用领域特别是组织再生具有潜在的应用前景。     

GelMA的合成、表征及在3D生物打印领域的研究进展

甲基丙烯酰明胶(GelMA)是一种基于明胶的工程材料,已被证明可用于组织工程、药物输送、细胞培养和3D打印等领域,多种基于GelMA的生物墨水已得到了开发和应用.本文综述了GelMA的合成和性能表征,以及在3D生物打印组织工程领域的研究及应用进展,以期为GelMA更进一步的利用提供参考.     

3D生物打印技术综述

3D生物打印是当前快速成型发展具有前景的领域之一,是融合生物学、材料学、制造学、生命科学为一体的交叉技术。该技术在组织工程和再生医学方面迅速发展,使打印组织器官成为可能。该篇文章对生物打印技术方法分为DBB、EBB、LBB三类进行概述,总结了生物打印的发展现状,介绍了生物打印技术的前沿：多材料打印及4D打印。     

3D生物打印中细胞活力的研究进展

3D生物打印是将细胞、生长因子和生物材料结合在一起,制造出模仿自然组织特征的生物医学部件,近年,该技术已广泛应用于组织工程相关研究中.生物墨水是3D生物打印的基础,细胞是生物墨水的重要组成部分,也是构建组织器官的关键之一,细胞活力是影响3D生物打印成功的决定因素,但3D生物打印过程较复杂,多种因素可影响细胞活力及其生物...     

3D打印技术在生物骨支架制备中的研究进展

3D打印技术是一种基于计算机设计,逐层叠加的快速成型技术。本文综述了近年来3D打印在制备生物骨支架中的应用,以及如何通过3D打印技术调控生物骨支架的力学性能及生物相容性。当前主要通过光固化立体印刷、选择性激光烧结、熔融沉积成型以及生物3D打印技术制备生物骨支架;通过控制生物骨支架的支架结构和孔隙率对其性能进行调控。迄今为止,3D打印技术在生物骨支架领域已经得到广泛的应用,但是仍存在一些问题有待进一步研究。     

3D打印高分子材料在医疗中的应用与发展趋势

3D打印,又称增材制造,始于20世纪80年代.经过近40年来的发展,此技术在生物医疗、工业制造、航空航天、文化创意等方面获得普遍应用.由于其独特的制造方法,为制药、医疗开辟新思路,其中,3D打印技术及3D成型生物医用高分子材料成为近年来研究热点.这种技术及3D成型材料被应用于医疗器械、药物载体、组织器官修复、体外细胞培...     

基于电场驱动喷射微纳3D打印的生物支架制备工艺

支架的结构与规格对于细胞的形态具有完全不同的影响,其规格尺寸与细胞特征尺寸(如神经细胞,胞体尺寸一般为20μm)的符合程度是衡量生物支架性能的关键指标,但是,目前的技术在制备小孔径、结构均匀的多层生物支架领域中仍存在一系列问题。因此,提出了一种基于电场驱动喷射微纳3D打印技术(EFD)和对称打印原理制备小孔径、结构均匀的多层生物支架的新方法,通过实验分析电压、速度、背压等工艺参数对打印结果的影响,优化多层生物支架的打印方案,最后,将聚乳酸(PLA)作为打印材料,成功制备纤维直径为20μm、周期为60μm、孔径为40μm的组织工程支架。     

3D打印技术在生物医学工程中的应用与研究

3D打印技术起源较早,但真正得到广泛应用与研究是在技术手段不断发达的当下。3D打印技术打破了人们对于成像技术的认知,其通过三维立体打印为人们提供了各式各样的产品。3D打印技术当前在生物制造领域中的应用较为广泛,实际可操作性也较高,为生物医学工程形成了许多新技术与新产品。     

Current Advances in 3D Bioprinting for Cancer Modeling and Personalized Medicine

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.     

Tissue-Specific Decellularized Extracellular Matrix Bioinks for Musculoskeletal Tissue Regeneration and Modeling Using 3D Bioprinting Technology

The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.     

3D Bio-Printability of Hybrid Pre-Crosslinked Hydrogels

Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing shape fidelity of the scaffolds, various percentages of Carboxymethyl Cellulose (CMC) (viscosity enhancer) and different calcium salts (CaCl₂ and CaSO₄, physical cross-linkers) were mixed into alginate before extrusion to realize shape fidelity. The overall solid content of Alginate-Carboxymethyl Cellulose (CMC) was limited to 6%. A set of rheological tests, e.g., flow curves, amplitude tests, and three interval thixotropic tests, were performed to identify and compare the shear-thinning capacity, gelation points, and recovery rate of various compositions. The geometrical fidelity of the fabricated scaffolds was defined by printability and collapse tests. The effect of using multiple cross-linkers simultaneously was assessed. Various large-scale scaffolds were fabricated (up to 5.0 cm) using a pre-crosslinked hybrid. Scaffolds were assessed for the ability to support the growth of Escherichia coli using the Most Probable Number technique to quantify bacteria immediately after inoculation and 24 h later. This pre-crosslinking-based rheological property controlling technique can open a new avenue for 3D bio-fabrication of scaffolds, ensuring proper geometry.     

Improving Printability of Digital-Light-Processing 3D Bioprinting via Photoabsorber Pigment Adjustment

Digital-light-processing (DLP) three-dimensional (3D) bioprinting, which has a rapid printing speed and high precision, requires optimized biomaterial ink to ensure photocrosslinking for successful printing. However, optimization studies on DLP bioprinting have yet to sufficiently explore the measurement of light exposure energy and biomaterial ink absorbance controls to improve the printability. In this study, we synchronized the light wavelength of the projection base printer with the absorption wavelength of the biomaterial ink. In this paper, we provide a stepwise explanation of the challenges associated with unsynchronized absorption wavelengths and provide appropriate examples. In addition to biomaterial ink wavelength synchronization, we introduce photorheological measurements, which can provide optimized light exposure conditions. The photorheological measurements provide precise numerical data on light exposure time and, therefore, are an effective alternative to the expendable and inaccurate conventional measurement methods for light exposure energy. Using both photorheological measurements and bioink wavelength synchronization, we identified essential printability optimization conditions for DLP bioprinting that can be applied to various fields of biological sciences.     

Bioprinting of Cartilage with Bioink Based on High-Concentration Collagen and Chondrocytes

The study was aimed at the applicability of a bioink based on 4% collagen and chondrocytes for de novo cartilage formation. Extrusion-based bioprinting was used for the biofabrication. The printing parameters were tuned to obtain stable material flow. In vivo data proved the ability of the tested bioink to form a cartilage within five to six weeks after the subcutaneous scaffold implantation. Certain areas of cartilage formation were detected as early as in one week. The resulting cartilage tissue had a distinctive structure with groups of isogenic cells as well as a high content of glycosaminoglycans and type II collagen.     

Current Advances in 3D Tissue and Organ Reconstruction

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.     

Printing perfusable and permeable vascular structure by controlled cross-linking

Vascular structure is indispensable for nutrition supply of 3D bioprinted organs. Coaxial extrusion is a routine way to generate vascular structure, however, the tubular size is fixed in this case. This study presented a simple and flexible method to develop perfusable and permeable vascular structure with controllable tubular diameter and wall thickness. A 3D bioprinter was used to extrude a gelatin/sodium alginate rod into the CaCl₂ solution. The polymerization occurred from outside to inside of the rod extruded. Then, the rod extruded was pulled out from the CaCl₂ solution and ceased polymerization. After washed away the inner uncross-linked part, a tube was obtained. The tubular diameter and wall thickness can be controlled by adjusting polymerization time. Finally, a layer of endothelial cells (HUVECs) was attached on the surface of the inner wall of the extruded tube using a novel sacrificial method.     

Polymeric Hydrogels for In Vitro 3D Ovarian Cancer Modeling

Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic remodeling that actively promotes tumor initiation, progression, and metastasis. Despite the fact that traditional 2D cell culture systems have led to relevant medical advances in cancer research, 3D cell culture models could open new possibilities for the development of an in vitro tumor microenvironment more closely reproducing that observed in vivo. The implementation of materials science and technology into cancer research has enabled significant progress in the study of cancer progression and drug screening, through the development of polymeric scaffold-based 3D models closely recapitulating the physiopathological features of native tumor tissue. This article provides an overview of state-of-the-art in vitro tumor models with a particular focus on 3D OC cell culture in pre-clinical studies. The most representative OC models described in the literature are presented with a focus on hydrogel-based scaffolds, which guarantee soft tissue-like physical properties as well as a suitable 3D microenvironment for cell growth. Hydrogel-forming polymers of either natural or synthetic origin investigated in this context are described by highlighting their source of extraction, physical-chemical properties, and application for 3D ovarian cancer cell culture.     

Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering

Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (−10 °C cryogenic plate, 40–80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts’ proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks.     

三维设计方法在水泥工厂设计中的应用

主要介绍三维设计方法和设计工具,以及三维设计的应用特征和优势,探讨三维设计技术在水泥工程设计中的应用前景和应用方法。