Additive manufacturing (AM) alias 3D printing translates computer-aided design (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D scan, or tomography data, AM builds objects layer by layer without the need for molds or machining. AM enables decentralized fabrication of customized objects on demand by exploiting digital information storage and retrieval via the Internet. The ongoing transition from rapid prototyping to rapid manufacturing prompts new challenges for mechanical engineers and materials scientists alike. Because polymers are by far the most utilized class of materials for AM, this Review focuses on polymer processing and the development of polymers and advanced polymer systems specifically for AM. AM techniques covered include vat photopolymerization (stereolithography), powder bed fusion (SLS), material and binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM), extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D bioprinting....

Polymers for 3D Printing and Customized Additive Manufacturing

The use of 3D printing for rapid tooling and manufacturing has promised to produce components with complex geometries according to computer designs. Due to the intrinsically limited mechanical properties and functionalities of printed pure polymer parts, there is a critical need to develop printable polymer composites with high performance. 3D printing offers many advantages in the fabrication of composites, including high precision, cost effective and customized geometry. This article gives an overview on 3D printing techniques of polymer composite materials and the properties and performance of 3D printed composite parts as well as their potential applications in the fields of biomedical, electronics and aerospace engineering. Common 3D printing techniques such as fused deposition modeling, selective laser sintering, inkjet 3D printing, stereolithography, and 3D plotting are introduced. The formation methodology and the performance of particle-, fiber- and nanomaterial-reinforced polymer composites are emphasized. Finally, important limitations are identified to motivate the future research of 3D printing.

3D printing of polymer matrix composites: A review and prospective

http://www.tissueeng.net/lab/papers/1-s2.0-S014296121500719X-main.pdf

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

BACKGROUND Hydrogels are formed through the cross-linking of hydrophilic polymer chains within an aqueous microenvironment. The gelation can be achieved through a variety of mechanisms, spanning physical entanglement of polymer chains, electrostatic interactions, and covalent chemical cross-linking. The water-rich nature of hydrogels makes them broadly applicable to many areas, including tissue engineering, drug delivery, soft electronics, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. The lack of desired dynamic cues and structural complexity within the hydrogels has further limited their functions. Broadened applications of hydrogels, however, require advanced engineering of parameters such as mechanics and spatiotemporal presentation of active or bioactive moieties, as well as manipulation of multiscale shape, structure, and architecture. ADVANCES Hydrogels with substantially improved physicochemical properties have been enabled by rational design at the molecular level and control over multiscale architecture. For example, formulations that combine permanent polymer networks with reversibly bonding chains for energy dissipation show strong toughness and stretchability. Similar strategies may also substantially enhance the bonding affinity of hydrogels at interfaces with solids by covalently anchoring the polymer networks of tough hydrogels onto solid surfaces. Shear-thinning hydrogels that feature reversible bonds impart a fluidic nature upon application of shear forces and return back to their gel states once the forces are released. Self-healing hydrogels based on nanomaterial hybridization, electrostatic interactions, and slide-ring configurations exhibit excellent abilities in spontaneously healing themselves after damages. Additionally, harnessing techniques that can dynamically and precisely configure hydrogels have resulted in flexibility to regulate their architecture, activity, and functionality. Dynamic modulations of polymer chain physics and chemistry can lead to temporal alteration of hydrogel structures in a programmed manner. Three-dimensional printing enables architectural control of hydrogels at high precision, with a potential to further integrate elements that enable change of hydrogel configurations along prescribed paths. OUTLOOK We envision the continuation of innovation in new bioorthogonal chemistries for making hydrogels, enabling their fabrication in the presence of biological species without impairing cellular or biomolecule functions. We also foresee opportunities in the further development of more sophisticated fabrication methods that allow better-controlled hydrogel architecture across multiple length scales. In addition, technologies that precisely regulate the physicochemical properties of hydrogels in spatiotemporally controlled manners are crucial in controlling their dynamics, such as degradation and dynamic presentation of biomolecules. We believe that the fabrication of hydrogels should be coupled with end applications in a feedback loop in order to achieve optimal designs through iterations. In the end, it is the combination of multiscale constituents and complementary strategies that will enable new applications of this important class of materials.

/pdf/advances-in-engineering-hydrogels-1gju2afbgf.pdf

Advances in engineering hydrogels

With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering - the combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue - is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three-dimensional tissue-like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell-laden hydrogels are commonly used in biofabrication and are termed "bioinks". Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three-dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically-relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico-chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a "printable" hydrogel that supports cell adhesion, migration, and differentiation will significantly advance this exciting and promising approach for tissue engineering.

/pdf/25th-anniversary-article-engineering-hydrogels-for-52t0ojjbic.pdf

25th Anniversary Article: Engineering Hydrogels for Biofabrication

A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering

The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability

The synthesis and evaluation of gelatin acrylamide as an alternative to the well-established gelatin methacrylamide are reported. High-resolution magic angle spinning NMR is used for the quantitative determination of the chemical cross-linking density. The gelatin acrylamide precursors reveal enhanced cross-linking in terms of reactivity and double bond conversion, resulting in stronger networks. Remarkably, even at very low double bond conversions, ≈5%, gel fractions of ≈40% are obtained. The cross-linked networks are also reviewed in the framework of the rubber elasticity and thermodynamic swelling theories to estimate important nanostructural properties. Preliminary cell tests revealed that highly viable (>90%) cell-laden constructs are obtained.

Quantitative Contrasts in the Photopolymerization of Acrylamide and Methacrylamide‐Functionalized Gelatin Hydrogel Building Blocks

In the last decade, substantial research in the field of post-plasma grafting surface modification has focussed on the introduction of carboxylic acids on surfaces by grafting acrylic acid (AAc). In the present work, we report on an alternative approach for biomaterial surface functionalisation. Thin poly-e-caprolactone (PCL) films were subjected to a dielectric barrier discharge Ar-plasma followed by the grafting of 2-aminoethyl methacrylate (AEMA) under UV-irradiation. X-ray photoelectron spectroscopy (XPS) confirmed the presence of nitrogen. The ninhydrin assay demonstrated, both quantitatively and qualitatively, the presence of free amines on the surface. Confocal fluorescence microscopy (CFM), atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to visualise the grafted surfaces, indicating the presence of pAEMA. Static contact angle (SCA) measurements indicated a permanent increase in hydrophilicity. Furthermore, the AEMA grafted surfaces were applied for comparing the physisorption and covalent immobilisation of gelatin. CFM demonstrated that only the covalent immobilisation lead to a complete coverage of the surface. Those gelatin-coated surfaces obtained were further coated using fibronectin. Osteosarcoma cells demonstrated better cell-adhesion and cell-viability on the modified surfaces, compared to the pure PCL films.

Post-Plasma Grafting of AEMA as a Versatile Tool to Biofunctionalise Polyesters for Tissue Engineering

The main challenge in hepatic tissue engineering is the fast dedifferentiation of primary hepatocytes in vitro. One successful approach to maintain hepatocyte phenotype on the longer term is the cultivation of cells as aggregates. This paper demonstrates the use of an agarose micro-well chip for the high throughput generation of hepatocyte aggregates, uniform in size. In our study we observed that aggregation of hepatocytes had a beneficial effect on the expression of certain hepatocyte specific markers. Moreover we observed that the beneficial effect was dependent on the aggregate dimensions, indicating that aggregate parameters should be carefully considered. In a second part of the study, the selected aggregates were immobilized by encapsulation in methacrylamide-modified gelatin. Phenotype evaluations revealed that a stable hepatocyte phenotype could be maintained during 21 days when encapsulated in the hydrogel. In conclusion we have demonstrated the beneficial use of micro-well chips for hepatocyte aggregation and the size-dependent effects on hepatocyte phenotype. We also pointed out that methacrylamide-modified gelatin is suitable for the encapsulation of these aggregates.

https://biblio.ugent.be/publication/5721564/file/5721578.pdf

Thomas Billiet

Papers

A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering

The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability

Quantitative Contrasts in the Photopolymerization of Acrylamide and Methacrylamide‐Functionalized Gelatin Hydrogel Building Blocks

Post-Plasma Grafting of AEMA as a Versatile Tool to Biofunctionalise Polyesters for Tissue Engineering

High Throughput Micro-Well Generation of Hepatocyte Micro-Aggregates for Tissue Engineering