Bioprinting最新文献

Chronic liver disease and related disorders are responsible for millions of deaths each year worldwide. In clinical practice, liver transplantation is recognized as an effective means of saving the lives of patients with severe complications. The shortage of organ donors has necessitated the development of bioengineered therapies that promote regeneration of the defective site and the creation of closely mimicking in vitro models for early prediction of disease states, hepatotoxicity testing, and accurate diagnostics. Despite tremendous research efforts, bioengineering of fully functional livers, detailed information on rare pathological mechanisms, and reliable bioartificial tissue-based therapies remain limited. On the other hand, 2D monolayer culture techniques are too simple to mimic and reproduce the functional characteristics of the liver accurately, its structural microenvironment, and the dynamic situation of cells in vivo. Therefore, tissue engineering-based 3D constructs outperform 2D culture systems. In this review, we provide insight into liver-related health complications, and the use of different cell types for tissue engineering. We also assess the current state of materiobiology and bioengineering technologies for fabricating 3D constructs. Afterward, we highlight the recent progress in liver tissue engineering, and outline the most relevant studies applying co-culture systems, spheroids, and organoid approaches, microfluidics, and 3D-bioprinting techniques. Finally, current dilemmas and possible future directions are explored.

This study aims to enhance the mechanical properties of 3D-printed scaffolds by optimizing a composite of Poly-ε-caprolactone (PCL), poly-hydroxybutyrate (PHB), and synthetic fluorapatite (FHAp) using Response Surface Methodology (RSM). The research targets the intricate relationships between PCL, PHB, and FHAp concentrations, crucial for achieving optimal tensile, compressive, and flexural strengths. The solvent-cast process successfully yielded FHAp-reinforced PCL composites, confirmed by XRD and FTIR spectra. The findings indicate that an optimal PHB content of over 15 % wt/v and PCL under 10 % wt/v significantly enhance tensile strength, achieving values up to 48 MPa. Compressive strength peaked at PHB concentrations of 13–16 % wt/v and PCL concentrations of 9–13 % wt/v, showcasing effective stress transmission, with the highest recorded value being 90 MPa. Flexural strength exceeded 100 MPa with lower concentrations of PCL and PHB, emphasizing the need for a balance of rigidity and flexibility. The study identifies the optimum composition for these mechanical properties at PCL 9.432 % wt/v, PHB 16.568 % wt/v, and FHAp 24.933 % wt/v, crucial for advanced biomedical implant applications.

This article examines 3D-printed structures that have self-healing properties. Additive manufacturing, also known as additive printing or 3D printing, is a sophisticated and adaptable technology that enables rapid, on-demand manufacturing of solid items made through a construction process based on a virtual computer-aided design (CAD) model. A technique known as 3D printing (3DP) enables the rapid creation of complex geometric shapes with previously unimaginable precision and performance. However, the availability of tunable-quality materials, especially those developed for additive manufacturing, remains a barrier to the widespread use of 3DP technology. This may increase the lifetime and performance of structural elements and even enable the propagation of living tissues for use in biomedical applications, including organ printing. This study discusses and analyzes the most relevant findings from the recent publication of 3D printable and self-healing polymer materials, by providing a chemical and physical self-healing process that may be used in 3D printing, as well as drug production and drug delivery devices. Finally, a critical discussion of the current landscape and possible development scenarios will take place.

In recent years, great efforts have been spent to create engineered muscle constructs recapitulating the 3D architecture and applying external stimulations. In this regard, tissue engineering approaches could be very promising in regenerating skeletal muscle, in which bioprinting techniques have produced encouraging results especially regarding 3D architecture. Tensile stimuli showed a fundamental role in regulating the behavior of muscle cells both in terms of 3D organizations and protein expression. Despite this promising premise, the combination of 3D bioprinting and mechanical stimulation has been poorly investigated, calling for novel approaches dealing with the mechanical stimulation of the 3D bioprinted construct and the integration of the bioprinting phase into the stimulation device. To this aim, the present work proposes the design, manufacturing, and benchmarking of a bioprinting-integrated mechanical platform conceived for mechanically stimulating a 3D muscle model directly printed into the bioreactor to foster the integration of printing and stimulation. The study consists of three main steps: 1) the design, fabrication, and mechanical characterization of stretchable supports suitable for bioprinting and long-term cell culture; 2) the design, assisted by computational tools, and the fabrication of the smart Petri dish containing the stimulation mechanism and of the final cyclic mechanical platform; 3) the in-vitro validation of the proposed platform in terms of transmission of the mechanical stimulation to the 3D construct and the biological effect of dynamic culture on 3D bioprinted muscle cells. The results highlighted excellent viability and demonstrated that the external stimulus influences the murine myoblasts behavior already after 7 days of culture. In conclusion, prototypes are now available of a mechanical platform that integrates the 3D bioprinting and is capable of stimulating 3D biological constructs for applications in the field of muscle tissue engineering.

The composition of soft tissues in mammals can be simplified as approximately 60–65 % water, 16 % protein, 16 % fat, 1 % carbohydrate, and trillions of cells. This report brings together unpublished results from a collaborative efforts of 10 research groups over the past five years, all dedicated to producing mammalian tissues through extrusion-based bioprinting. What unified these studies was a common approach, with a shared bioink composition consisting of gelatin, alginate, and fibrinogen, and a post-printing consolidation strategy involving transglutaminase crosslinking, calcium chelation, and thrombin-mediated fibrin production. The range of Young’s moduli achievable was 0.17–105 kPa, perfectly align with of tissue properties.

By consolidating the findings of these studies, it was conclusively demonstrated that bioprinting and culturing all 19 cells tested from 14 different organs was indeed achievable. These remarkable outcomes were attributed not only to the bio-inspired nature of the common bioink but also to its unique rheological properties, such as significant shear-thinning and a sufficiently high static yield stress.

The majority of these cells exhibited behaviours consistent with their natural in vivo environments. Clearly identifiable microstructures and organizations showcased intricate morphogenesis mechanisms resulting in the formation of micro-tubules, micro-vessels, and micro-acini. It is now evident that microextrusion bioprinting, especially when using bio-inspired bioink formulations, represents a promising avenue for generating a wide range of mammalian soft tissues.

The complications in liver functioning arising due to hepatic disorders are a major contributor of mortality worldwide, with transplantation being the only resort for patients with severe cases. Due to liver's direct role in drug metabolism, fabrication on functional liver tissue models is eventually becoming a necessity for high-throughput drug screening applications. Tissue engineering approaches could provide an answer to the drooping supply by allowing for the fabrication and printing of a fully operational, implantable, and sustainable liver tissues. Moreover, such bioengineered tissues can be made to resemble their native counterparts. 3D bioengineering strategies including 3D bioprinting and microfluidic-based liver-on-chip models stand out in this regard due to their potential to create physiologically relevant microenvironment/niches for the biofabricated tissues. Nonetheless, achieving vascularization in such bioengineered tissues is still considered one of the biggest bottlenecks for engineers. The incorporation of blood vessels made from endothelial cells (ECs) is addressed in vasculogenesis while angiogenesis investigates generating new vessels from preexisting vasculature. Overall, vascularization is essential for the survival, function, and integration of bioprinted liver tissues, making it a key focus area in the development of functional liver substitutes for regenerative medicine and drug testing applications. This review paper focuses on the opportunities and difficulties of performing vascularization and angiogenesis in 3D bioengineered-based liver tissue models. Particularly, this paper delves into aspects such as methods of bioengineering, bioinks used, analysis techniques, advantages, limitations, and prospects related to 3D bioengineered liver tissue models as well as vascular engineering in general.

Temperature Controlled Cryoprinting (TCC), is a tissue engineering technique wherein each deposited voxel is frozen with precise control over cooling rates and the direction of freezing. This control allows for the generation of ice crystals with controlled shape and orientation. Recently we found that the macroscale fidelity of the TCC print is substantially improved by using a 3D printing ink composed of a mixture of two compounds: one that solidifies through chemical crosslinking (sodium alginate) and another that solidifies through physical (thermal) effects (agar). In this study we examine the hypothesis that the combination of sodium alginate and agar, affects also the fidelity of the microstructure and thereby the diffusivity of the scaffold. The ability of this technology to generate controlled diffusivity within the tissue scaffold was examined with a directional solidified TCC sample using fluorescence recovery after photobleaching (FRAP) and scanning electron microscope (SEM). We find that the diffusion coefficient in m²/s × 10⁻¹⁰ is: 1.62 $\pm$ 1.27 for the unfrozen sample, 2.40 $\pm 1$.54 for the rapidly frozen sample and $9.72\pm$ 4.50 for the slow frozen sample. This points to two conclusions. One is that the diffusivity is slow frozen samples is higher than that in unfrozen samples and in rapidly frozen sample. A second observation is that a relatively narrow range of diffusivity variance was obtained when using 2%w/v sodium alginate and 2%w/v of agar. However, when the concentration of agar was reduced to 0.5w/v a much wider spread of diffusivities was measure, $4.07\pm 1$.65. This suggests that the addition of agar has also an effect on the microscale fidelity, and consequently the diffusivity. The anisotropic diffusion properties of TCC-printed directional solidification samples were also validated through both FRAP and SEM.

While β titanium alloys have garnered extensive attention as a new generation of biomedical materials designed to mitigate stress shielding due to their low modulus, the realm of additive manufacturing for these alloys is still in its nascent stages. This study focuses on the additive manufacturing of Ti–35Nb–5Ta–7Zr alloy powder via directed energy deposition (DED). The primary objectives were assessing the feasibility of employing DED for this alloy powder and identifying processing parameters to achieve nearly dense components. Systematic exploration of the effect of various processing parameters was performed, and the resultant impact on the densification of the produced specimens was studied. Comprehensive analysis of the microstructure, mechanical properties, electrochemical behavior, and cell studies of fully dense sample coupons were performed. These fully dense samples were found to exclusively comprise the β phase of titanium, resulting in a reduced modulus of elasticity (approximately 44–47 GPa) resulting in high yield strength to elastic modulus ratio. Microstructural examinations revealed the presence of both columnar and equiaxed dendrites, with grains transitioning from columnar to equiaxed (known as CET). Electrochemical testing of the coupons indicated exceptional corrosion resistance in the additively manufactured TNZT alloy. Pre-osteoblasts cultured on the alloys showed good attachment, viability, and growth to confirm cytocompatibility. These findings unveiled the attainment of high strength, favorable ductility, a low elastic modulus, excellent corrosion resistance, and cytocompatibility in dense samples created via DED of Ti–35Nb–5Ta–7Zr. These outcomes hold immense significance for the production of patient-specific medical implants manufactured from β-Ti alloys.

Three-dimensional (3D) printing has the potential to be used for rapid-prototyping and inexpensive fabrication of bioreactors for advanced cell and tissue culture. However, the suitability of materials used for 3D printing these bioreactors that will be in direct contact with cells and culture media remains to be established. Many of the most common low-cost materials have not been thoroughly tested under stringent cell culture conditions, especially not with highly sensitive human cell types, such as induced pluripotent stem cells (hiPSCs). This study aims to characterize some 3D printed plastics, such as thermoplastics and photopolymers, focusing on the toxicity/cytocompatibility of the materials as assessed by hiPSC viability, retention of pluripotency, and cardiogenic differentiation potential. Experiments were conducted in a manner that simulates contact between 3D printed plastics and cell culture media, as found in a 3D printed bioreactor. Both photopolymers tested here reduced the viability of hiPSCs, but not of primary human fibroblasts, highlighting the importance of carrying out these tests with the cells of interest. The thermoplastics did not adversely affect stem cell viability, pluripotency, or cardiac differentiation potential. However, except for Nylon12, all thermoplastics deformed during autoclaving, leading us to choose Nylon12 as the most suitable material for bioreactor fabrication. This study represents a step forward in the use of 3D printing for the rapid, low-cost fabrication of custom-designed bioreactors.

Additive manufacturing and 3D printing is being widely adopted by the medical industry. This study provides a comprehensive overview of the current state of 3D printing technology in NHS trusts across the UK. Data was collected through a survey using the freedom of information act. The survey revealed that 53 NHS trusts (∼25 %) across the UK are utilising the technology, with a diverse range of strategies and applications. The most common application was the creation of guides and models, used for pre-operative planning, intraoperative guidance, and educational purposes. The study also highlights the regulatory and ethical considerations involved in 3D printing in healthcare. The findings indicate that there are no 3D printing specific standards or guidelines being followed for medical devices and therefore underscores the need for clear and consistent regulatory guidelines to be established. As the 3D printing technology continues to advance, its applications in healthcare are expected to expand rapidly, warranting further research into its impact on patient outcomes and healthcare costs.