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PLA molds and silicone stamps of other different vascular designs. The left four PLA molds were printed with negative S-shaped circuitous networks, multiple parallel channels, and traditional trunk-branch structures, respectively. The right four silicone stamps with different positive vascular designs were created against the corresponding left molds. Color images available online at www.liebertpub.com/3dp
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The size of engineered tissue constructs is mainly constrained by diffusion limitations in the bulk materials. It has been proposed that engineering of constructs with embedded perfusable vascular networks might advance the engineering of larger tissue constructs and allow novel applications for biomedical studies. However, the progress in this fie...
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... simple trunk-branch vascular structure in this study was originally chosen as a proof of principle. Besides, other designs were printed that shows the versatility of this ap- proach (Fig. 2). Negative, multi-S shape, circuitous networks, multiple parallel channels, and traditional trunk-branch structures could be designed and printed within PLA molds, which allows the silicone stamps to be molded with accurate positive designs. Based on 3D printing, this approach pro- vides more complexity and flexibility in vascular ...
Citations
... Both can be controlled by spatio-temporal release of angiogenic factors like vascular endothelial growth factor (VEGF) 77,80 . In the former, prevascularization of tissues occurs, e.g. by co-culturing endothelial cells and stem cells in the bulk material of the biofabricated structure 81,82 . Extrinsic vascularization relies on implantation of a fabricated porous structure 21 . ...
Recent advances in tissue engineering and biofabrication technology have yielded a plethora of biological tissues. Among these, engineering of bioartificial muscle stands out for its exceptional versatility and its wide range of applications. From the food industry to the technology sector and medicine, the development of this tissue has the potential to affect many different industries at once. However, to date, the biofabrication of cultured meat, biorobotic systems, and bioartificial muscle implants are still considered in isolation by individual peer groups. To establish common ground and share advances, this review outlines application-specific requirements for muscle tissue generation and provides a comprehensive overview of commonly used biofabrication strategies and current application trends. By solving the individual challenges and merging various expertise, synergetic leaps of innovation that inspire each other can be expected in all three industries in the future. This review discusses the recent advances in the engineering of bioartificial muscle. The applications highlighted include cultured meat, biorobotics, and muscle implants.
... We chose PDMS, a silicone-based polymer as a main component of our bioreactor technology for its excellent processability and biocompatibility. It can be easily casted, sterilized by autoclaving, is permeable to oxygen, and is transparent for realtime observation (Friend and Yeo, 2010;Liu et al., 2016). The bioreactors were designed with several parts and molds including culture chamber and inserts through the open access software Tinkercad 1 (Figures 1 A,E). ...
... Following the molding process, hydrogel tubes with different outer and inner diameters were created. Resulting hydrogel tubes showed consistence with the 3D geometries as designed through Tinkercad (Figures 3A,B; Liu et al., 2016). Vessel structures were created with multiple layers (Figure 3C). ...
Tissue engineering in combination with stem cell technology has the potential to revolutionize human healthcare. It aims at the generation of artificial tissues that can mimic the original with complex functions for medical applications. However, even the best current designs are limited in size, if the transport of nutrients and oxygen to the cells and the removal of cellular metabolites waste is mainly dependent on passive diffusion. Incorporation of functional biomimetic vasculature within tissue engineered constructs can overcome this shortcoming. Here, we developed a novel strategy using 3D printing and injection molding technology to customize multilayer hydrogel constructs with pre-vascularized structures in transparent Polydimethysiloxane (PDMS) bioreactors. These bioreactors can be directly connected to continuous perfusion systems without complicated construct assembling. Mimicking natural layer-structures of vascular walls, multilayer vessel constructs were fabricated with cell-laden fibrin and collagen gels, respectively. The multilayer design allows functional organization of multiple cell types, i.e., mesenchymal stem cells (MSCs) in outer layer, human umbilical vein endothelial cells (HUVECs) the inner layer and smooth muscle cells in between MSCs and HUVECs layers. Multiplex layers with different cell types showed clear boundaries and growth along the hydrogel layers. This work demonstrates a rapid, cost-effective, and practical method to fabricate customized 3D-multilayer vascular models. It allows precise design of parameters like length, thickness, diameter of lumens and the whole vessel constructs resembling the natural tissue in detail without the need of sophisticated skills or equipment. The ready-to-use bioreactor with hydrogel constructs could be used for biomedical applications including pre-vascularization for transplantable engineered tissue or studies of vascular biology.
... In vivo experiments showed that the scaffold could release BMP-2 over a long time, which enabled control of the osteogenesis rate. Bendtsen and others [85] used a new type of alginate-polyvinyl alcohol (PVA)-hydroxyapatite (HA) hydrogel and mouse skull 3 T3-E1 (MC3T3) cells as the raw materials to prepare 3D scaffolds with high shape accuracy. It PEG has good hydrophilicity and biocompatibility. ...
Appropriate scaffolds for tissue-engineered bone not only require mechanical strength, but also conditions that promote new bone growth. Bone tissue engineering scaffolds should establish the internal pore structure of the scaffolds and promote new bone growth. Additive manufacturing technology is widely used in the field of bone tissue engineering because it can directly and accurately construct the pore structure in 3D space, ensure internal connectivity of the scaffolds, and directly use biological materials. This paper reviews the development of additive manufacturing technology for bone tissue engineering. The differences between various additive manufacturing technologies are reviewed, with emphasis on the application of new technologies and materials. This paper also reviews the modeling processes used in bone tissue engineering, with emphasis on the optimization of the architectural design to achieve gradient structure and improved porosity and mechanical properties. Finally, this paper summarizes the 3D bioprinting technology that has fluid containing nutrients, matrix, and cells as constituent materials. Current problems and directions for the future development of additive manufacturing technology in the field of bone tissue engineering are also discussed.
... For engineering muscle constructs in vitro, one of the major limitations is the lack of vascularization [128]. It has been shown that myoblasts need to be within 150 m of the supply route for oxygen and nutrients (typically vessels) to survive, proliferate, and differentiate [129]. ...
... Another possibility is a coculture with endothelial cells [135]. In addition, integration of vascular networks into the bioengineered scaffold by microfluidic methods or bioprinting is expected to provide solutions in the near future [128,[136][137][138]. Maybe the combination of several approaches will eventually solve the current vascularization deficit of the designed tissues. ...
Skeletal muscle has the capacity of regeneration after injury. However, for large volumes of muscle loss, this regeneration needs
interventional support. Consequently, muscle injury provides an ongoing reconstructive and regenerative challenge in clinical
work. To promote muscle repair and regeneration, different strategies have been developed within the last century and especially
during the last few decades, including surgical techniques, physical therapy, biomaterials, and muscular tissue engineering as
well as cell therapy. Still, there is a great need to develop new methods and materials, which promote skeletal muscle repair and
functional regeneration. In this review, we give a comprehensive overview over the epidemiology of muscle tissue loss, highlight
current strategies in clinical treatment, and discuss novel methods for muscle regeneration and challenges for their future clinical
translation.
... The microfluidic-based BBB models discussed in Section 6.1 have inspired researchers to develop new advanced biomimetic BBB models. Several groups including ours have used advanced tissue engineering approaches to develop multilayer vessels supporting the engineering of multicellular hydrogels (Fig. 6a) [289][290][291][292]. ...
The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.
One of the most common types of 3D printing technologies involves is inkjet printing due to its numerous advantages, including low cost, programmability, high resolution, throughput, and speed. Inkjet printers are also capable of fabricating artificial tissues with physiological characteristics similar to those of the living tissues. These artificial tissues are used for disease modeling, drug discovery, drug screening, as well as replacements for diseased or damaged tissues. This paper reviews recent advancements in one of the most common 3D printing technologies, inkjet dispensing technology. We briefly consider common printing techniques, including fused deposition modeling (FDM), stereolithography (STL), and inkjet printing. We briefly discuss various steps in inkjet printing, including droplet generation, droplet ejection, interaction of droplets on substrates, drying, and solidification. We also discuss various parameters that affect the printing process, including ink properties (e.g., viscosity and surface tension), physical parameters (e.g., internal diameter of printheads), and actuation mechanisms (e.g., piezoelectric actuation and thermal actuation). Through better understanding of common 3D printing technologies and the parameters which influence the printing processes, new types of artificial tissues, disease models, as well as structures for drug discovery and drug screening may be prepared. This review considers future directions in inkjet printing research that are focused on enhancing the resolution, printability, and uniformity of printed structures.
This is a comprehensive overview of the epidemiology of each type of soft tissue defects and the current successful applications of regenerative medicine and methods of advancing the regeneration of these tissues. The authors discuss the epidemiology of soft tissue defects, successful application of regenerative treatments, challenges associated with regeneration, surgical techniques, scaffold-based treatments, drug-based therapy, cell-based therapy, and other treatments. There are unsolved questions discussed, such as vascularization in the process of regeneration, functional tissue regeneration, immune system problems, and problems with biomaterials, regulations and ethics. An outlook is given on necessary future developments for successful translation of advanced concepts of regenerative medicine to day-to-day routine in plastic surgery.
In this chapter, we will focus on how 3D printer technology is transforming traditional medicine into a personalized approach, giving an overview of the technology advancement and its clinical applications. First, we will discuss why personalization in medicine is required, its benefits for the patients and how 3D printing technology can address this need for the patient specific treatment solutions. Basic capabilities of 3D printers and the three most common 3D printing technologies used in medical applications will be covered as well. The second section focuses on current and potential medical applications of 3D printing. The main medical applications can be arranged into three categories: (1) 3D bioprinting of organs and tissues; (2) patient specific medical devices: prosthetics and implants; and (3) 3D models for surgical preparation. Here, we will discuss 3D printing of living cells, in situ 3D bioprinting directly to the defect site, some successful cases of the implantation of various 3D constructs and the production of precise anatomical models for surgical trainings. Lastly, we will highlight challenges and emerging technology developments for the printing of functional organ constructs and medical devices.
