Cryo-3D Printing of Hierarchically Porous Polyhydroxymethylene Scaffolds for Hard Tissue Regeneration

High molecular weight polyhydroxymethylene (PHM) has a repeat unit identical to that of low molecular weight sugar alcohols and exhibits carbohydrate-like properties. Herein, cryogenic extrusion-based 3D printing is combined with a phase separation in water to fabricate hierarchically porous PHM scaffolds containing interconnected macro-, micro-, and nanopores. As PHM is infusible and insoluble in common solvents, its precursor polyvinylene carbonate (PVCA) dissolved in dimethylsulfoxide (DMSO) is used to 3D print hierarchically porous PVCA scaffolds that are converted into PHM by hydrolysis without impairing the pore architectures. Similar to low-temperature deposition manufacturing, the PVCA/DMSO freezes on a build platform at −78 °C. However, instead of removing the frozen solvent by sublimation, the frozen scaffold is immersed in water to recover DMSO and to effect phase separation by precipitation. However, the computer-guided printhead pathway controls macropore formation phase separation of frozen PVCA/DMSO upon contact with water accounts for simultaneous micro- and nanopore formation. Contrary to 3D printing of PVCA/DMSO at ambient temperature, this cryo-3D printing process does not require shear thinning additives and affords significantly improved build precision with macropore sizes variable between 200 and 1500 µm. Cryo-3D-printed PHM scaffolds are biocompatible and promote osteoblast proliferation.     

Bioprinting and Tissue Engineering: Recent Advances and Future Perspectives

Bioprinting in tissue engineering applies 3D printing technologies towards the development of precisely designed scaffolds for tissue repair and organ replacement. The printed scaffolds may incorporate polymeric constituents together with biological payloads, including cells and biochemically active additives. The scaffolds can be designed with spatial precision, achieving both biochemical and biophysical heterogeneity that mimic the extracellular environment of the body’s tissues. Recent advances in 3D bioprinting have applied a strategy of controlling physical properties together with bioactivity to influence specific interactions with cellular systems, including spatial and temporal patterns of biochemical and biomechanical cues that regulate cell behavior and improve tissue integration. Important new advances in tissue engineering have now been realized based on these approaches, and clinical applications for printed scaffolds continue to drive further improvements to 3D bioprinter technologies.     

Four-Dimensional Printing and Shape Memory Materials in Bone Tissue Engineering

The repair of severe bone defects is still a formidable clinical challenge, requiring the implantation of bone grafts or bone substitute materials. The development of three-dimensional (3D) bioprinting has received considerable attention in bone tissue engineering over the past decade. However, 3D printing has a limitation. It only takes into account the original form of the printed scaffold, which is inanimate and static, and is not suitable for dynamic organisms. With the emergence of stimuli-responsive materials, four-dimensional (4D) printing has become the next-generation solution for biological tissue engineering. It combines the concept of time with three-dimensional printing. Over time, 4D-printed scaffolds change their appearance or function in response to environmental stimuli (physical, chemical, and biological). In conclusion, 4D printing is the change of the fourth dimension (time) in 3D printing, which provides unprecedented potential for bone tissue repair. In this review, we will discuss the latest research on shape memory materials and 4D printing in bone tissue repair.     

Solvent-Cast 3D Printing of Biodegradable Polymer Scaffolds

3D printing is a popular fabrication technique because of its ability to produce complex architectures. Melt-based 3D printing is widely used for thermoplastic polymers like poly(caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) because of their low processing temperatures. However, traditional melt-based techniques require processing temperatures and pressures high enough to achieve continuous flow, limiting the type of polymer that can be printed. Solvent-cast printing (SCP) offers an alternative approach to print a wider range of polymers. Polymers are dissolved in a volatile solvent that evaporates during deposition to produce a solid polymer filament. SCP, therefore, requires optimizing polymer concentration in the ink, print pressure, and print speed to achieve desired print fidelity. Here, capillary flow analysis shows how print pressure affects the process-apparent viscosity of PCL, PLA, and PLGA inks. Ink viscosity is also measured using rheology, which is used to link a specific ink viscosity to a predicted set of print pressure and print speed for all three polymers. These results demonstrate how this approach can be used to accelerate optimization by significantly reducing the number of parameter combinations. This strategy can be applied to other polymers to expand the library of polymers printable with SCP.     

Cryogenic 3D Printing of w/o Pickering Emulsions Containing Bifunctional Drugs for Producing Hierarchically Porous Bone Tissue Engineering Scaffolds with Antibacterial Capability

How to fabricate bone tissue engineering scaffolds with excellent antibacterial and bone regeneration ability has attracted increasing attention. Herein, we produced a hierarchical porous β-tricalcium phosphate (β-TCP)/poly(lactic-co-glycolic acid)-polycaprolactone composite bone tissue engineering scaffold containing tetracycline hydrochloride (TCH) through a micro-extrusion-based cryogenic 3D printing of Pickering emulsion inks, in which the hydrophobic silica (h-SiO₂) nanoparticles were used as emulsifiers to stabilize composite Pickering emulsion inks. Hierarchically porous scaffolds with desirable antibacterial properties and bone-forming ability were obtained. Grid scaffolds with a macroscopic pore size of 250.03 ± 75.88 μm and a large number of secondary micropores with a diameter of 24.70 ± 15.56 μm can be fabricated through cryogenic 3D printing, followed by freeze-drying treatment, whereas the grid structure of scaffolds printed or dried at room temperature was discontinuous, and fewer micropores could be observed on the strut surface. Moreover, the impartment of β-TCP in scaffolds changed the shape and density of the micropores but endowed the scaffold with better osteoconductivity. Scaffolds loaded with TCH had excellent antibacterial properties and could effectively promote the adhesion, expansion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells afterward. The scaffolds loaded with TCH could realize the strategy to “kill bacteria first, then induce osteogenesis”. Such hierarchically porous scaffolds with abundant micropores, excellent antibacterial property, and improved bone-forming ability display great prospects in treating bone defects with infection.     

Biomimetic Platforms for Tissue Engineering

Bioengineering platforms that combine cell/tissue specific transport and signaling with precise control of culture conditions and multiparametric insights into the cell function are critical to our efforts to study tissue development, regeneration, and disease under conditions that predict the human in vivo context. Because living cells respond to the entire context of their environment – in vivo and in vitro, under normal and pathological conditions – the biological foundation of our bioengineering designs that is often described as the “biomimetic paradigm” is critical for unlocking the biological potential of the cells. This brief review focuses on some of the key principles for designing and using biologically inspired engineering platforms. Four examples are used to illustrate the designs and applications of biomimetic platforms.     

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.     

混凝土3D打印材料及3D打印模板技术应用进展

混凝土3D打印是现代数字化制造的典型代表,因其智能化、个性化、绿色建造的工艺优势受到广泛关注。作为一种新型建造方式,3D打印为建筑业带来了颠覆性的影响,并对传统混凝土材料提出了全新的挑战。如何提升混凝土材料与3D打印技术的适应性,实现3D打印技术在建筑中的广泛应用是人们普遍关注的焦点。本文概述了混凝土3D打印技术的发展历程,系统论述了混凝土3D打印材料在流变性、可挤出性、可建造性以及力学性能方面的研究现状,同时,介绍了3D打印模板技术在装饰及异型构筑物上的典型应用,以期为混凝土3D打印的研究与未来工程发展提供一定的参考与借鉴。     

三维打印生物材料的发展现状

随着组织工程和再生医学不断进步,3D打印技术被用于开发和制造由仿生天然和合成材料组成的仿生支架。讨论3D打印"生物墨水"的进步和发展趋势,对3D打印多功能生物材料的发展具有积极意义。     

Naturally Derived Maleic Chitosan/Thiolated Sodium Hyaluronate Hydrogels as Potential 3D Printing Tissue Engineering Materials

3D printing is an attractive method to accurately construct artificial organs or alternative materials with complicated structures and functional performance. Naturally derived hydrogels have emerged as promising materials for the preparation of biomimetic 3D organization or scaffolds by 3D printing due to their good biocompatibility, high water content, and fascinating 3D network. However, the poor printing properties and weak structural stability of naturally derived hydrogels limit their applications. In this study, photopolymerizable hydrogels are designed based on maleic chitosan (MCS) and thiolated sodium hyaluronate (SHHA). The Michael addition between MCS and SHHA improves the viscosity of the mixed solution. Moreover, it benefits the 3D printing process, followed by photopolymerization (acrylate-thiol step-chain polymerization and acrylate–acrylate chain polymerization) to form a stable covalent network rapidly. The rheological property, swelling behaviors, microstructure, and in vitro degradation are tuned by adjusting the molar ratio of the thiol group and acrylate group. In addition, MCS/SHHA hydrogel scaffolds with good accuracy and enhanced structural stability are prepared using extrusion-based 3D printing and photopolymerization technology. The hydrogels display excellent cytocompatibility and can support adherence of L929 cells, which can be used as prospective materials for tissue engineering applications.     

组织工程用生物材料的研究与开发

本文介绍了组织工程和生物材料的发展现状,探讨了组织工程相关生物材料的研究方向。     

Existing and Novel Biomaterials for Bone Tissue Engineering

The treatment of bone defects remains one of the major challenges in modern clinical practice. Nowadays, with the increased incidence of bone disease in an aging population, the demand for materials to repair bone defects continues to grow. Recent advances in the development of biomaterials offer new possibilities for exploring modern bone tissue engineering strategies. Both natural and synthetic biomaterials have been used for tissue repair. A variety of porous structures that promote cell adhesion, differentiation, and proliferation enable better implant integration with increasingly better physical properties. The selection of a suitable biomaterial on which the patient’s new tissue will grow is one of the key issues when designing a modern tissue scaffold and planning the entire treatment process. The purpose of this article is to present a comprehensive literature review of existing and novel biomaterials used in the surgical treatment of bone tissue defects. The materials described are divided into three groups—organic, inorganic, and synthetic polymers—taking into account current trends. This review highlights different types of existing and novel natural and synthetic materials used in bone tissue engineering and their advantages and disadvantages for bone defects regeneration.     

Nanomaterials for 3D Printing of Polymers via Stereolithography: Concept,Technologies, and Applications

Stereolithography (SLA) is an additive manufacturing method with one of the highest accuracies (down to 100 nm) of all solid freeform techniques and has been used in various areas, such as medicine, automotive, aerospace, electronics, and others. However, most resins available nowadays are derived from petroleum. Its toxicity, low biocompatibility, and growing environmental concerns are limiting its application. This review discusses the development of biobased and biocompatible materials for different SLA processes as well as the usage of nanocomposites to increase their applicability. A comprehensive overview of the SLA technologies, photopolymerization chemistry, and resin properties are also provided. Finally, various examples using different types of materials are explored, to show the current and future capabilities of the SLA technique.     

高聚物的新型3D打印材料开发进展

综述了一般3D打印技术的概念、产业及其发展。重点介绍了高聚物在3D打印材料中的应用。持续跟踪结果表明:一批新型高聚物的3D打印材料推向市场,一批国际知名化工公司也在积极介入3D打印业务。     

Fiber-Based Composite Tissue Engineering Scaffolds for Drug Delivery

Drug delivery through tissue-engineered scaffolds provides a composite approach to address the regenerative limitations of simple material implantation, providing expanded avenues for therapeutic tissue-repair strategies in the clinic. Both nano- and microfibrous scaffolds generated by a variety of techniques have been investigated for their potential in drug-delivery applications. While nanofibers mimic the structure and organization of natural extracellular matrix, microfibers provide more sustained release of drugs, larger pores to facilitate cell infiltration, and improved mechanical support. Various methods exist to embed drugs within the fiber matrix to modulate the release kinetics specific to the tissue-engineering application. The current article reviews the established and emerging fabrication methods for drug-loaded fiber-based scaffolds and addresses how further combination into composite scaffolds can enhance drug delivery and tissue regeneration.     

Advanced 3D Magnetic Scaffolds for Tumor-Related Bone Defects

The need for bone substitutes is a major challenge as the incidence of serious bone disorders is massively increasing, mainly attributed to modern world problems, such as obesity, aging of the global population, and cancer incidence. Bone cancer represents one of the most significant causes of bone defects, with reserved prognosis regarding the effectiveness of treatments and survival rate. Modern therapies, such as hyperthermia, immunotherapy, targeted therapy, and magnetic therapy, seem to bring hope for cancer treatment in general, and bone cancer in particular. Mimicking the composition of bone to create advanced scaffolds, such as bone substitutes, proved to be insufficient for successful bone regeneration, and a special attention should be given to control the changes in the bone tissue micro-environment. The magnetic manipulation by an external field can be a promising technique to control this micro-environment, and to sustain the proliferation and differentiation of osteoblasts, promoting the expression of some growth factors, and, finally, accelerating new bone formation. By incorporating stimuli responsive nanocarriers in the scaffold’s architecture, such as magnetic nanoparticles functionalized with bioactive molecules, their behavior can be rigorously controlled under external magnetic driving, and stimulates the bone tissue formation.     

3D打印高分子材料研究进展

主要介绍了聚乳酸(PLA),聚己内酯(PCL),聚醚醚酮(PEEK),聚碳酸酯(PC)和丙烯腈-丁二烯-苯乙烯塑料(ABS)等在3D打印技术中的应用,并且综述了这些材料相应的改性方法以及改性材料的应用性能。通过对已有3D打印材料的改性和扩充,3D打印产品将可以广泛应用到医疗、生物组织工程、工业、军事、航空航天等领域,3D打印技术也将成为一种主流的塑料加工技术。     

3D打印塑料材料在汽车配件设计中的应用

近年来,汽车产业出现了以塑代钢的轻量化趋势,随着3D打印技术的不断发展,3D打印塑料材料在汽车配件设计中应用广泛,能够有效地节省汽车研发周期,削减成本。概述了3D打印塑料材料的现状,包括其种类、形态及改进技术,及其对于汽车配件设计的影响;介绍了3D打印塑料材料在汽车配件设计中的应用,并对其在汽车配件设计中的未来发展趋势进行了探讨。     

Bioprinting of Thermoresponsive Hydrogels for Next Generation Tissue Engineering: A Review

Bioprinting is a breakthrough technology that integrates living cells, biomaterials, and a robotic dispensing system to create complex structures that mimic original tissues and organs. One of the main components of bioprinting is bioink and hydrogel is essential in bioink formulation. In bioprinting, hydrogel should have good biocompatibility, provide good resolution, and have sufficient mechanical strength to support printed structures. Recently, thermoresponsive hydrogels have gained more and more attention due to their unique characteristic of tunable sol‐gel (liquid to solid phase) transition when temperature is changed, and many biomedical applications from drug delivery devices to tissue scaffolds have demonstrated the potentials of bioprinted thermosresponsive constructs. In this review, we discuss bioprintable thermoresponsive hydrogels with a particular focus on their gelation mechanisms, fabrication strategies using bioprinter and applications. The future prospects of the bioprinting‐based use of thermoresponsive hydrogels for next generation tissue engineering have also been discussed.

     

组织工程支架材料研究进展

组织工程支架材料在组织工程研究中起中心作用，不仅为特定的细胞提供结构支撑作用，而且还起到模板作用，引导组织再生和控制组织结构。寻找一种既有良好生物相容性和生物降解性又具有特定形状和连通三维多孔结构的支架材料是组织工程的重要方面。本文概述了几种常用的组织工程支架材料，并对组织工程支架材料目前存在的问题作了分析、对其发展趋势进行了展望。