3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances.

Organs are complex systems composed of different cells, proteins and signalling molecules that are arranged in a highly ordered structure to orchestrate a myriad of functions in our body. Biofabrication strategies can be applied to engineer 3D tissue models in vitro by mimicking the structure and function of native tissue through the precise deposition and assembly of materials and cells. This approach allows the spatiotemporal control over cell–cell and cell–extracellular matrix communication and thus the recreation of tissue-like structures. In this Review, we examine biofabrication strategies for the construction of functional tissue replacements and organ models, focusing on the development of biomaterials, such as supramolecular and photosensitive materials, that can be processed using biofabrication techniques. We highlight bioprinted and bioassembled tissue models and survey biofabrication techniques for their potential to recreate complex tissue properties, such as shape, vasculature and specific functionalities. Finally, we discuss challenges, such as scalability and the foreign body response, and opportunities in the field and provide an outlook to the future of biofabrication in regenerative medicine. Biofabrication can be applied to replicate tissues and organs for regenerative medicine and for the creation of 3D in vitro tissue models. In this Review, the recent advances in biomaterials and biofabrication technologies are discussed, and challenges and opportunities are highlighted.

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Biofabrication strategies for 3D in vitro models and regenerative medicine

The native tissues are complex structures consisting of different cell types, extracellular matrix materials, and biomolecules. Traditional tissue engineering strategies have not been able to fully reproduce biomimetic and heterogeneous tissue constructs because of the lack of appropriate biomaterials and technologies. However, recently developed three-dimensional bioprinting techniques can be leveraged to produce biomimetic and complex tissue structures. To achieve this, multicomponent bioinks composed of multiple biomaterials (natural, synthetic, or hybrid natural-synthetic biomaterials), different types of cells, and soluble factors have been developed. In addition, advanced bioprinting technologies have enabled us to print multimaterial bioinks with spatial and microscale resolution in a rapid and continuous manner, aiming to reproduce the complex architecture of the native tissues. This review highlights important advances in heterogeneous bioinks and bioprinting technologies to fabricate biomimetic tissue constructs. Opportunities and challenges to further accelerate this research area are also described.

Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs.

3D bioprinting of functional tissue models for personalized drug screening and in vitro disease modeling

Three-dimensional (3D) bioprinting has recently advanced as an important tool to produce viable constructs that can be used for regenerative purposes or as tissue models. To develop biomimetic and sustainable 3D constructs, several important processing aspects need to be considered, among which crosslinking is most important for achieving desirable biomechanical stability of printed structures, which is reflected in subsequent behavior and use of these constructs. In this work, crosslinking methods used in 3D bioprinting studies are reviewed, parameters that affect bioink chemistry are discussed, and the potential toward improving crosslinking outcomes and construct performance is highlighted. Furthermore, current challenges and future prospects are discussed. Due to the direct connection between crosslinking methods and properties of 3D bioprinted structures, this Review can provide a basis for developing necessary modifications to the design and manufacturing process of advanced tissue-like constructs in future.

Crosslinking Strategies for 3D Bioprinting of Polymeric Hydrogels

Due to its relatively low level of antigenicity and high durability, titanium has successfully been used as the major material for biological implants. However, because the typical interface between titanium and tissue precludes adequate transmission of load into the surrounding bone, over time, load-bearing implants tend to loosen and revision surgeries are required. Osseointegration of titanium implants requires presentation of both biological and mechanical cues that promote attachment of and trigger mineral deposition by osteoblasts. While many factors contribute to differentiation, the relative importance of the various cues is unclear. To substantially improve osseointegration of titanium implants, we generated a gelatin methacryloyl (GelMA) scaffold, using an extrusion-based 3D bioprinter, which can be directly printed on and grafted to the titanium implant surface. We demonstrate that this scaffold is able to trigger mineral deposition of both MG63 osteoblasts and primary normal human osteoblasts in the absence of any exogenous osteogenic factors. Films of the same formulation failed to promote mineral deposition suggesting that the three dimensional scaffold was able to tip the balance in favor of differentiation despite other potentially unfavorable differentiation cues of the material. We further show that these GelMA lattices can be directly grafted to titanium alloy and are secure in vitro over a period of seven weeks. When grafted within a groove system, the GelMA hydrogel is protected from shearing forces in a marrow implantation model. This prepares the way for osteogenic coatings to be directly manufactured on the implant surface and packaged for surgery.

https://iopscience.iop.org/article/10.1088/1758-5090/aa53bd/pdf

3D bioprinting of GelMA scaffolds triggers mineral deposition by primary human osteoblasts.

Experimental Investigations on the Machinability of Tungsten Carbides in Orthogonal Cutting with Diamond-coated Tools☆

Tool Technologies for Milling of Hardmetals and Ceramics

The call for green technologies, new improved and lighter materials in combination with more economic manufacturing processes are current challenges in nearly all industrial fields. Notably, this applies in the turbo machinery manufacturing for the energy and aviation industry, where legal and ecological regulations and restrictions result in the need for radical new product concepts. However, the development of such products is significantly triggered by the application of innovative materials, which is the reason why turbo machinery manufacturers are permanently looking for advanced materials, like nickel or titanium based alloys. Certainly the properties of these alloys result in complex thermo-mechanical loads on the tools during the machining processes, which lead to increased tool wear. Finally high tool demand, long machining times and bad surface qualities of the manufactured parts are the consequence. To overcome these drawbacks the design of milling strategies, that are able to realize good surfaces in combination with high material removal rates at acceptable tooling costs are an inevitable must. However, the layout of high performing machining processes assumes comprehensive understanding of the procedures and interdependencies, which occur during the machining process between the tool and the work piece. On this basis the realization of advanced machining operations becomes feasible within very short time, to fulfill short time-to-markets, which are required in the addressed sectors. In this paper an innovative approach will be presented showing how fundamental process knowledge can be determined and used for the design of high-performing, multi-axis milling processes for machining advanced materials. Therefore, investigations regarding the fields of process modelling, simulation, material analysis and analogy milling tests are performed. The presented approach will be verified with data of machining Inconel 718 and Inconel DA 718.

https://conferences.sun.ac.za/index.php/doie/coma13/paper/download/327/284

Innovative Approach for a Fast and Knowledge-Based Milling Process Design of Advanced Materials

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3D bioprinting of GelMA scaffolds triggers mineral deposition by primary human osteoblasts.

Experimental Investigations on the Machinability of Tungsten Carbides in Orthogonal Cutting with Diamond-coated Tools☆

Tool Technologies for Milling of Hardmetals and Ceramics

Innovative Approach for a Fast and Knowledge-Based Milling Process Design of Advanced Materials