Bioprinting最新文献

Given their enormous flexibility and freedom of design, 3D printing technologies have been applied in various fields, such in the production of high value-added products via biocatalysis. By combining the ease of construction of additive manufacturing with the characteristic selectivity of enzymatic processes, 3D printing offers a series of novel possibilities that have streamlined the screening of fundamental parameters for optimization of enzyme immobilization and process sustainability. This review aimed to examine scientific studies published on the topic between 2016 and 2023 and assess the most critical factors determining the use of 3D printing technologies in the manufacture of enzyme immobilization supports. A discussion is presented on the main advantages and opportunities of commonly used 3D printing techniques and raw materials, as well as on support geometry and chemical functionalization methods. In the current literature, there is great interest in combining the benefits of 3D printing technologies and moldable raw materials for the development of reinforced biopolymers with improved mechanical properties and minimal environmental impacts.

Algae is a renewable source of various materials that are suitable for 3D printing. Taking a step towards sustainability, the continuously growing industry of 3D printing calls for novel green materials/inks with stable mechanical properties. This paper aims to investigate the 3D printability of algae-based materials and their potential for 4D bioprinting. The sources, printability, and properties of algae-based synthetic polymers, natural hydrogels, and algae cells were reviewed. 4D printability was also explored in terms of hydrogel responsiveness to various types of stimuli and in terms of cell/tissue maturation, and relevant recent progress was reviewed. Results show that PHAs (Polyhydroxyalkanoates) from algae can replace fossil-derived PHAs because they have similar mechanical properties whilst being more environmentally friendly. Algae can also produce a wide range of hydrogel-forming polymers, of which many are already being used as 3D printing inks while others are yet to be developed to suit the printing specifications. Several hydrogels also demonstrate stimuli-responsiveness which make them suitable for 4D printing. Further research is required to overcome the mechanical instability and slow stimuli-responsiveness of natural hydrogels.

The evolution of meta-biomaterials has opened up exciting new opportunities for mass personalisation of biomedical devices. This research paper details the development of a CoCrMo meta-biomaterial structure that facilitates personalised stiffness-matching while also exhibiting near-zero auxeticity. Using laser powder bed fusion, the porous architecture of the meta-biomaterial was characterised, showing potential for near-zero Poisson's ratio. The study also introduces a novel surrogate model that can predict the porosity ($\phi$), yield strength (${\sigma }_y$), elastic modulus ($E$), and negative Poisson's ratio ($-\upsilon$) of the meta-biomaterial, which was achieved through prototype testing and numerical modelling. The model was then used to inform a multi-criteria desirability objective, revealing an optimum near-zero $-\upsilon$ of −0.037, with a targeted stiffness of 17.21 GPa. Parametric analysis of the meta-biomaterial showed that it exhibited $-\upsilon$, $\phi$, ${\sigma }_y$ and $E$ values ranging from −0.02 to −0.08, 73.63–81.38%, 41–64 MPa, and 9.46–20.6 GPa, respectively. In this study, a surrogate model was developed for the purpose of generating personalised scenarios for the production of bone scaffolds. By utilising this model, it was possible to achieve near-zero $-\upsilon$ and targeted stiffness personalisation. This breakthrough has significant implications for the field of bone tissue engineering and could pave the way for improved patient outcomes. The presented methodology is a powerful tool for the development of biomaterials and biomedical devices that can be 3D printed on demand for load-bearing tissue reconstruction. It has the potential to facilitate the creation of highly tailored and effective treatments for various conditions and injuries, ultimately enhancing patient outcomes.

Biomimetic composites for bone tissue engineering have outstanding potential to improve bone grafting and in vitro drug testing. Although bioactive fillers play a crucial role in those composites, the impact of their physical properties on final products is not fully understood, particularly when using solvent-based extrusion bioprinting (SBEB). In our study, we used ball-milled bioactive glass and hydroxyapatite powders to examine how particle size distribution impacts the flow, mechanical, and biological properties of biomaterials produced via SBEB. The polymeric matrix of polycaprolactone (PCL) was dissolved in solvents, and the fillers were mixed in different proportions to optimize the biomaterial ink's extrudability and interphase bonding. The printed samples were subjected to mechanical testing, solvent removal, and cytotoxicity analysis. Our results show that powders milled at 25 Hz for 10 min in a dry medium produced homogeneous size distributions with low agglomeration. A 50% PCL and 50% w/w polymer-to-filler ratio in an 80% w/v solid–liquid proportion generated the best extrudability and interphase bonding. Particle type affected the modulus of elasticity, and smaller aggregate sizes increased ultimate tensile strength. Moreover, the specific size of the filler particles and their structure could influence their affinity to solvents, thereby resulting in variation in the solvent removal process after ethanol rinsing. Beyond that, the biomaterials were non-cytotoxic and demonstrated high cell viability. Those findings highlight the importance of controlling the filler size distribution to optimize the mechanical, rheological, and biological properties of biomaterials fabricated using SBEB for bone tissue engineering applications.

Deformable structures have been actively developed for several biomedical applications including drug delivery and tissue engineering using 3D-bioprinting methods. However, structural shape-transformation usually consists of a series of bending behaviors in response to external stimuli, which require complex aggregation and multi-materials design. To overcome these complexities, this work explores an alternative approach using only a single hydrogel-based material to realize such bending mechanisms. Numerical simulations are first implemented to realize bending deformation by spatially assigning distinct material parameters to different sections of the structure. The bending phenomenon is also shown experimentally using hydrogel-based biomaterial inks. Specifically, a deformable structure is fabricated by finely controlling different post-processing conditions such as cooling time, crosslinking duration, and heating rate during swelling to mimic the effect of different material parameters. Moreover, the bending deformation can be further analyzed using computer vision methods to inversely determine the desired material coefficients in the simulation. Relationships among bending mechanisms, material parameters, and post-processing procedures are found and shown to affect the final bending orientation. These results yield insightful approaches to the inverse design of functional biomedical devices with desired deformation behavior.

This study aimed to prototype oral dental films (ODFs) loaded with diclofenac sodium (DS) using two different grades of CompactCel® polymers through a semi-solid extrusion (SSE) bioprinter. This three-dimensional (3D) printed ODFs were developed for the treatment of toothaches with immediate and sustained release features. Two different grades of CompactCel® polymers, CompactCel® P 002.02 SR and CompactCel® P Clear 194.04 SIL, with sustained and immediate release features, respectively, were explored in this study. A blend of CompactCel® polymers was found to be capable of forming hydrogels with the addition of dibutyl phthalate (DBP) as a plasticizer to improve the foldability/flexibility of the developed ODFs. ODFs were 3D printed using an SSE bioprinter by varying the amount of DBP. All 3D bio-printed ODFs were analyzed systematically in terms of in vitro physicochemical characteristics, including drug content, drug release, and release kinetics models. The in vitro release graph of DS from ODFs showed an initial burst release of around 50–70% in 20 min followed by the sustained release of up to 150 min for all the formulations. The prototype ODFs showed dual drug delivery features in terms of initial fast release followed by sustained release. Thus, these ideal biomaterial combinations were explored for the first time to establish not only their pharmaceutical 3D bioprinting capabilities but also their potential for drug delivery applications.

Facilitating effective mixing of two or more functional polymers remains a challenge when translating in situ-crosslinking click chemistry hydrogels to extrusion bioprinting applications. In this work, the conventional flush coaxial needle was modified to introduce a mixing region to promote the mixing of low-viscosity hydrazide and aldehyde-functionalized poly (oligoethylene glycol methacrylate) (POEGMA) polymers that form dynamic hydrazone bonds upon crosslinking. The inclusion of the mixing region significantly reduced the spreading of the printed fibers and improved the homogeneity of both the printed hydrogel and the encapsulated cells. Computational modeling based on non-Newtonian fluid behavior in the mixing zone confirmed that increasing the length of the mixing zone improved the mixing efficiency, a finding supported by experimental printing results. As such, particularly with less viscous bioinks like the oligomeric hydrazide/aldehyde-functionalized POEGMA polymers used herein, the inclusion of this mixing region provides an effective means of printing functional precursor polymers that can chemically crosslink upon mixing.

In this paper, a mist-based method for coaxial three-dimensional bioprinting of ionically crosslinking hydrogel hollow fibers is presented. Unlike current techniques of coaxial bioprinting that utilize the crosslinker in liquid or sacrificial form, the developed method introduces the core crosslinking agent in mist form. The use of mist as a core flow provides adequate pressure and sufficient crosslinking to maintain the tubular shape of a hollow fiber. Through controlled exposure of crosslinker, the developed system prevents poor resolution and layer adhesion caused by the accumulation of liquid crosslinker on the printbed. Furthermore, it eliminates additional processing steps, such as partial crosslinking of the hydrogel prior- or removal of sacrificial material post-printing. The printability and mechanical properties of hollow fiber scaffolds printed using various mist and hydrogel concentrations are studied. It is shown that mist concentration influences the gelation rate of the hollow fiber, impacting the shape fidelity, layer adhesion, and mechanical properties of the printed structures. Moreover, the effects of printing parameters, including the mist core pressure and hydrogel flowrate, on the diameter and wall thickness of the hollow fiber are investigated. Finally, scaffolds printed and crosslinked using mist exhibit over 90% cell viability. The developed mist-based coaxial system enables direct printing of continuous hollow fibers.

Patterned photocrosslinking has several uses in the biofabrication of microstructurally complex tissue constructs, through both photolithography of scaffolds and photoconjugation of cell adhesive and instructive moieties. Often the polymers used are modified by methacrylation while photoactivation requires ultraviolet light. In contrast, this study aimed to design, build and evaluate a low-cost platform to place photocrosslink patterns into unmodified collagen and gelatin hydrogels using visible light and ruthenium-mediated tyrosine crosslinking in a way compatible with cell culture and inverted microscopes commonly used in biological laboratories. A photoprinting module was constructed above an inverted microscope sample stage to be confocal with the imaging system. The module consists of a blue light emitting diode array, light pipe, diffuser, microelectronically controlled liquid crystal display as photomask, and focusing objective. Resulting Ruthenium-mediated photocrosslink patterns were visible in unmodified collagen and gelatin hydrogels due to altered local polymer network density and optical contrast. Green fluorescent protein was conjugated in patterns to both gelatin and collagen gels, dependent on light exposure, intensity, and polymer network density. Pattern resolution varied from 2.0 ± 0.5 μm to 102 ± 33 μm (mean ± standard deviation) dependent on the focusing objective magnification and the pattern used (display pixel versus diode element). Further, photocrosslink patterns placed in collagen hydrogels and incubated without rinsing in serum-containing media swelled over 20–48 h, breaking the collagen network and forming ∼50 μm diameter holes. Fibroblasts cultured in photopatterned collagen hydrogels aligned and moved on and around crosslinked regions, consistent with durotaxis and contact guidance. The platform for photocrosslinking described in this study will impact several research fields, notably bioprinting of microstructurally and mechanically complex tissue constructs.

Lattice structures are composed of interconnected porous unit cells that are arranged in a periodic and regular fashion. Their light wight and high specific strength alongside many other superior mechanical properties, have made them an excellent candidate for tissue engineering applications. In tissue engineering, porous structures (scaffolds) are employed for regeneration of living and healthy tissues and organs. Via their specific architecture, lattice structures can provide a proper environment for cells to attach to and colonize. Additive Manufacturing (AM) offers great flexibility in fabrication of lattice structures for tissue engineering. AM can apply complex design of unit cells and duplication patterns, to generate high quality lattice structures with good accuracy. In addition, biocompatibility and biodegradability of lattice structures that are main concerns in tissue engineering, can be addressed with a wide range of material choices in different AM methods. In this review, additive manufacturing of lattice structures in tissue engineering is discussed, with a focus on materials and AM methods that have been studied in the existing literature. Furthermore, various designs of unit cells in the AM of lattice structures, the effect of AM process parameters, challenges and future of this field are reviewed.