Bioprinting最新文献

Millions of people worldwide suffer from birth defects, trauma, or illness that affect their mental well-being, social interactions, professional life, finance, and life quality. Prosthesis revamps the standard of life for most affected people by restoring aesthetics and functions to anatomical parts where plastic surgery is unsuitable and costly. To overcome the issues of conventional fabrication such as lack of attachment, function, robustness, aesthetics, and cost, 3D printing could be a suitable technology to manufacture prosthesis products. However, 3D printing of prosthesis materials is currently in the very early phase of evolution and is facing various challenges, like limited 3D printing of compatible prosthesis materials, issues with printability, defects, and low mechanical strength in the printed parts. On the other hand, the interface and software for manufacturing maxillofacial prosthesis products are costly. This review article aims to address the challenges and opportunities associated with the 3D printing of maxillofacial prosthesis material using computer-aided design. The current advancements in the 3D printing of prosthesis materials is summarized and future prospectives of additive manufacturing of prosthesis materials are exhaustively discussed in order to encourage potential research in this area. Furthermore, the successful implementation of additive manufacturing techniques in prosthesis will enhance its potential in large-scale biomedical applications and scalable customization.

In this study, a foam-based method is developed for three-dimensional coaxial bioprinting of ionically crosslinking bioinks. This method introduces the crosslinker to the bioink in calcium chloride-albumin foam which eliminates the need for multiple crosslinking steps and offers an excellent control over the crosslinking rate and the diameter of the hollow fibers. The effects of the foam and alginate flow rates were investigated on the outer diameter and the wall thickness of the hollow fibers. Various structures were 3D printed and characterized by printability number and the method showed an excellent layer adhesion among printed layers. The effects of foam composition and the alginate concentration on the mechanical properties were assessed through breaking strain and filament collapse tests to determine the optimum composition for hollow fiber fabrication. The hollow fiber composed of 2% (w/v) sodium alginate that is crosslinked with a foam made of 1.07% (w/v) albumin and 1.07% (w/v) calcium chloride showed superior mechanical properties. Furthermore, the viability of co-incubation with Neuro-2a cells over seven days was investigated and no significant negative effect of the used concentrations of albumin and calcium chloride was observed on the viability of the cells.

Biocompatible fluorescent nanodiamonds (FNDs) were introduced into polycaprolactone (PCL) – the golden standard material in melt electrowriting (MEW). MEW is an advanced additive manufacturing technique capable of depositing high-resolution micrometric fibres. Due to the high printing precision, MEW finds growing interest in tissue engineering applications. Here, we introduced fluorescent nanodiamonds (FNDs) into polycaprolactone prior to printing to fabricate scaffolds for biomedical applications with improved mechanical properties. Further FNDs offer the possibility of their real-time degradation tracking. Compared to pure PCL scaffolds, the functionalized ones containing 0.001 wt% of 70 nm-diameter nanodiamonds (PCL-FNDs) showed increased tensile moduli (1.25 fold) and improved cell proliferation during 7-day cell cultures (2.00 fold increase). Furthermore, the addition of FNDs slowed down the hydrolytic degradation process of the scaffolds, accelerated for the purpose of the study by addition of the enzyme lipase to deionized water. Pure PCL scaffolds showed obvious signs of degradation after 3 h, not observed for PCL-FNDs scaffolds during this time. Additionally, due to the nitrogen-vacancy (NV) centers present on the FNDs, we were able to track their amount and location in real-time in printed fibres using confocal microscopy. This research shows the possibility for high-resolution life-tracking of MEW PCL scaffolds’ degradation.

Extrusion-based bioprinting (EBB) offers unique advantages for 3D printing of hydrogels including superior structural integrity, high cell density, and continuous deposition. Despite these advantages, the lack of mechanical stability of printed constructs limits the fabrication of high aspect ratio constructs using EBB. Due to this limitation, patterning macroscopic scaffolds to mimic anatomical structures of a high aspect ratio remains a challenge. For example, it is difficult for EBB to print hollow tubes of an appreciable length-to-width ratio without using complicated sacrificial materials in a multi-print process. By using gravity as a 5th-dimensional input (X, Y, Z, time, gravity), we were able to generate high aspect ratio structures without further complication of 3D printer mechanics. Using gravity-assisted bioprinting methods we routinely achieved aspect ratios greater than two times those of similar constructs printed without gravity assistance.

Particulate matter has been identified as a significant environmental threat to human health. As one of its components, copper oxide nanoparticles (CuO NP) have been found highly potent in cytotoxicity. However, the elucidation of its mechanism is still limited. This study investigated the toxicity of CuO NP toward a cardiac tissue. To better recapitulate the species-specific tissue phenotype and toxin response, we developed a human induced pluripotent stem cells (iPSC)-derived cardiac micro-tissue. With the precise deposition of the cell and scaffold material enabled by rapid 3D bioprinting, the cardiac micro-tissue showed a mature phenotype and was incorporated with a force gauge to enable contraction measurement. We discovered an LD₅₀ of 7.176 g/mL from the CuO NP treatment outcome of the micro-tissue with a downward trend in tissue force as toxicity increased. We also identified mitochondrial damage and activation of extrinsic apoptosis as a significant pathway to mediate the tissue toxicity.

3D bioprinting is a potential technique for developing functional 3D tissues for tissue engineering and regenerative medicine applications. Recently, the direct formation of 3D tissues on defect sites, known as in situ 3D bioprinting, has gained increasing attention to fulfill unmet needs. In situ 3D bioprinting has shown the capability of addressing problems, such as the need for invasive operations for transplantation and fabrication of sophisticated, irregularly shaped constructs, demonstrating its advantages over conventional methods. This review summarizes the two main approaches used for in situ bioprinting, namely robotic and handheld bioprinting. Besides, the latest advances in organ regeneration using this approach are discussed. Furthermore, some natural and synthetic materials used for in situ bioprinting are briefly presented.

The skin plays a vital role in several significant physiological functions, including wound healing. It is possible to regenerate the skin's epidermis and dermis layers using bio-printed skin substitutes in patients suffering from skin injuries. In-situ bioprinting has advanced significantly in recent years, enabling the usage of novel biomaterials and allowing the development of ‘biofabrication’ techniques that can resemble the biological, architectural, and functional complexity of native skin. This paper summarizes some of the most recent approaches to skin regeneration and in-situ bio-fabrication techniques. It also presents strategies and perspectives on triggering the proper regenerative response of the body through the tuned mechanical properties of the implant to recapitulate native physiology. Available materials for engineering ideal skin substitutes and reviewing the skin properties reported in the literature are also reported. Moreover, challenges and prospects in the clinical translation of in-situ bioprinting are also discussed.

Extrusion-based 3D bioprinting allows the 3D printing of bioinks, composed of cells and biomaterials, to mimic the complex 3D hierarchical structure of native tissues. Successful 3D bioprinting requires bioinks with specific properties, such as biocompatibility, printability, and biodegradability according to the desired application. In the present work, we aimed at developing a new versatile blend of gelatin methacryloyl-xanthan gum (GelMA-XG) suitable for extrusion-based 3D bioprinting with a straightforward process. To this end, we first optimized the process of gelatin methacryloyl (GelMA) synthesis by investigating the impact of different buffer solutions on the degree of functionalization, swelling degree, and degradation rate. The addition of xanthan gum (XG) enabled further tuning of biodegradability and an improvement of GelMA printability. Specifically, an optimal concentration of XG was found through rheological characterization and printability tests. The optimized blend showed enhanced printability and improved shape fidelity as well as its degradation products turned out to be non-cytotoxic, thus laying the foundation for cell-based applications. In conclusion, our newly developed biomaterial ink is a promising candidate for extrusion-based 3D bioprinting.

Tears of the meniscus are among the most commonly diagnosed knee injuries. Because most of the meniscus lacks the ability to self-heal due to its low vascularity, surgical intervention is needed in more than 85% of cases. Tissue-engineered meniscal implants may provide a treatment strategy that better supports healing and long-term health and mobility benefits. We used three-dimensional printing to develop a “universal” human meniscal tissue repair device that can be trimmed to match the corresponding area of damage debrided during the patient's surgical repair. Computer aided design software was used to design an adult meniscus of average shape based on published physical dimensions. To reproduce the natural fiber arrangement found in the meniscus, the tool path for 3D bioprinting was structured to use alternating layers of circumferential and radial extrusions. We also developed extrudable, shear thinning bioinks based on meniscus biochemical components, including collagen I methacrylate, collagen II, and chondroitin sulfate methacrylate. The combination of this tissue-specific bioink and the deposition pattern to build the meniscus are novel. Ink formulations were evaluated with rheology to assess the viscosity and post-gelling stiffness. Inks retained shape fidelity when thermally gelled after printing into a support bath, and the fabricated menisci maintained stable dimensions for up to 4 weeks post printing. Bioprinted menisci containing human mesenchymal stem cells were also dimensionally stable, and viable cells were present up to 4 weeks post printing. Increased glycosaminoglycan deposition was noted in the bioprinted meniscus over 21 days, and decorin and collagen type I gene expression increased. Compression testing demonstrated that Young's modulus approaches 100 kPa when molded as a solid object and 45 kPa when extruded into the meniscus shape. This 3D printed, anisotropic meniscus emulates the natural architecture and biochemical composition of the natural human meniscus and has potential to be developed into a device for use in treatment of meniscal injuries.

Regenerative medicine and tissue engineering are continuously advancing and utilizing new technologies to provide reliable solutions for replacing damaged tissues. Unlike subtractive manufacturing, additive manufacturing became an answer for creating complex shapes for many fields, such as tissue engineering, which requires the need to create body parts that are not geometrically simple. Three-dimensional (3D) bioprinting technology is a great additive manufacturing tool that will significantly benefit the field of regenerative medicine and tissue engineering once precision and feasibility are achieved. Printing a 3D structure narrows the range of material choices to meet the biomaterials criteria, including biocompatibility, biodegradability, printability, and low cytotoxicity. Hydrogels meet all requirements for biomaterials; however, they have weak mechanical properties that are hard to control, making it challenging to print a scaffold precisely, restricting their chance of being used as a potential reliable 3D bioprinting material. In this paper, composite scaffolds composed of calcium alginate/gelatin/κ-carrageenan are printed using an extrusion-based 3D bioprinter. Different concentrations of all three hydrogels are prepared and crosslinked with calcium chloride to transform it from sodium alginate/gelatin/κ-carrageenan to calcium alginate/gelatin/κ-carrageenan, then tested for their strength in tension. Printability is also tested for different concentrations to find the best printing parameters in terms of pressure, print speed, layer height, and printing temperature. The composite hydrogel mixture composed of 2.2% (w/v) calcium alginate/1% (w/v) gelatin/4% (w/v) κ-carrageenan exhibited a higher modulus of elasticity compared to the other tested concentrations and is printable using a 0.864 mm nozzle diameter, 62 °C printing temperature, and 48.2 kPa printing pressure.