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Journal ArticleDOI

3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion.

TL;DR: In this article, a combination of millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation.
Abstract: Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native-like millimetric vessels. This work presents a novel strategy aiming to create fully-engineered patient-specific thick tissue flaps.
Citations
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Journal ArticleDOI
TL;DR: Overall, this study reveals that the bone microenvironment‐mimetic dual‐drug delivery scaffold provides a promising strategy for bone defects treatment.
Abstract: Microchannel networks within engineered 3D scaffold can allow nutrient exchange and rapid blood vessels formation. However, fabrication of a bone microenvironment‐mimicking scaffold with hierarchical micro/nanofibrous and microchannel structures is still a challenge. Herein, inspired by structural and functional cues of bone remodeling, a microchannel networks‐enriched nanofibrous scaffold by using 3D printing and thermally induced phase separation techniques, which can facilitate cells migration and nutrients transportation, is developed. The customizable vascular‐like structure of polycaprolactone within the nanofibrous gelatin‐silica scaffold is fabricated using 3D‐printed sacrificial templates, while dimethyloxalylglycine (DMOG)‐loaded mesoporous silica nanoparticles (MSNs) located on the scaffold surface and bone forming peptide‐1 (BFP)‐loaded MSNs embedded in the scaffold are implemented for sequential release of DMOG and BFP. The cell experiments show that dual‐drug delivery scaffold (DBM/GP) promotes angiogenesis by stimulating migration, tube formation, and angiogenesis‐related genes/protein expression of endothelial cells, and osteogenesis by promoting osteo‐related genes expression and mineral deposition of osteoblasts. Additionally, DBM/GP scaffold facilitates the angiogenic activity of osteoblasts by activating phosphatidylinositol 3‐kinase/protein kinase B/hypoxia inducible factor‐1α pathway. Furthermore, enhanced vascularization and bone regeneration of DBM/GP scaffold are demonstrated via subcutaneous and skull defect models. Overall, this study reveals that the bone microenvironment‐mimetic dual‐drug delivery scaffold provides a promising strategy for bone defects treatment.

40 citations

Journal ArticleDOI
TL;DR: Modern trends in this arena of research are surveyed and the intricacies of new features to guide and prepare the sector for an Industry 5.0-ready healthcare system are summarised.
Abstract: Industry 4.0 in healthcare involves use of a wide range of modern technologies including digitisation, artificial intelligence, user response data (ergonomics), human psychology, the Internet of Things, machine learning, big data mining, and augmented reality to name a few. The healthcare industry is undergoing a paradigm shift thanks to Industry 4.0, which provides better user comfort through proactive intervention in early detection and treatment of various diseases. The sector is now ready to make its next move towards Industry 5.0, but certain aspects that motivated this review paper need further consideration. As a fruitful outcome of this review, we surveyed modern trends in this arena of research and summarised the intricacies of new features to guide and prepare the sector for an Industry 5.0-ready healthcare system.

35 citations

Journal ArticleDOI
TL;DR: In this paper , the authors highlight the materials advances that have enabled transformative progress in vascular engineering by ushering in new tools for both visualizing and building vasculature, including bioprinting, organoids and microfluidic systems, which have enabled the fabrication of 3D vascular topologies at a cellular scale with lumen perfusion.
Abstract: The survival of vertebrate organisms depends on highly regulated delivery of oxygen and nutrients through vascular networks that pervade nearly all tissues in the body. Dysregulation of these vascular networks is implicated in many common human diseases such as hypertension, coronary artery disease, diabetes and cancer. Therefore, engineers have sought to create vascular networks within engineered tissues for applications such as regenerative therapies, human disease modelling and pharmacological testing. Yet engineering vascular networks has historically remained difficult, owing to both incomplete understanding of vascular structure and technical limitations for vascular fabrication. This Review highlights the materials advances that have enabled transformative progress in vascular engineering by ushering in new tools for both visualizing and building vasculature. New methods such as bioprinting, organoids and microfluidic systems are discussed, which have enabled the fabrication of 3D vascular topologies at a cellular scale with lumen perfusion. These approaches to vascular engineering are categorized into technology-driven and nature-driven approaches. Finally, the remaining knowledge gaps, emerging frontiers and opportunities for this field are highlighted, including the steps required to replicate the multiscale complexity of vascular networks found in nature.

28 citations

Journal ArticleDOI
TL;DR: In this article , a guided overview of the recent advances in the programming of synthetic hydrogels that offer precise control over the spatiotemporal properties within cellular microenvironments, such as advances in cell-driven remodeling, bioprinting, or user-defined manipulation of properties (e.g., via light irradiation).

18 citations

Journal ArticleDOI
TL;DR: The current report outlines the 3D printing point-of-care concept in the field of oral and maxillofacial surgery, and indicates major clinical applications.
Abstract: Compared to traditional manufacturing methods, additive manufacturing and 3D printing stand out in their ability to rapidly fabricate complex structures and precise geometries. The growing need for products with different designs, purposes and materials led to the development of 3D printing, serving as a driving force for the 4th industrial revolution and digitization of manufacturing. 3D printing has had a global impact on healthcare, with patient-customized implants now replacing generic implantable medical devices. This revolution has had a particularly significant impact on oral and maxillofacial surgery, where surgeons rely on precision medicine in everyday practice. Trauma, orthognathic surgery and total joint replacement therapy represent several examples of treatments improved by 3D technologies. The widespread and rapid implementation of 3D technologies in clinical settings has led to the development of point-of-care treatment facilities with in-house infrastructure, enabling surgical teams to participate in the 3D design and manufacturing of devices. 3D technologies have had a tremendous impact on clinical outcomes and on the way clinicians approach treatment planning. The current review offers our perspective on the implementation of 3D-based technologies in the field of oral and maxillofacial surgery, while indicating major clinical applications. Moreover, the current report outlines the 3D printing point-of-care concept in the field of oral and maxillofacial surgery.

15 citations

References
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Journal ArticleDOI
TL;DR: 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation and developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
Abstract: Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

4,841 citations

Journal ArticleDOI
16 Sep 2011-Cell
TL;DR: The emerging principles of vascular growth provide exciting new perspectives, the translation of which might overcome the current limitations of pro- and antiangiogenic medicine.

2,278 citations

Journal ArticleDOI
TL;DR: An overview of the different types of scaffolds with their material properties is discussed and the fabrication technologies for tissue engineering scaffolds, including the basic and conventional techniques to the more recent ones, are tabulated.
Abstract: Current strategies of regenerative medicine are focused on the restoration of pathologically altered tissue architectures by transplantation of cells in combination with supportive scaffolds and biomolecules. In recent years, considerable interest has been given to biologically active scaffolds which are based on similar analogs of the extracellular matrix that have induced synthesis of tissues and organs. To restore function or regenerate tissue, a scaffold is necessary that will act as a temporary matrix for cell proliferation and extracellular matrix deposition, with subsequent ingrowth until the tissues are totally restored or regenerated. Scaffolds have been used for tissue engineering such as bone, cartilage, ligament, skin, vascular tissues, neural tissues, and skeletal muscle and as vehicle for the controlled delivery of drugs, proteins, and DNA. Various technologies come together to construct porous scaffolds to regenerate the tissues/organs and also for controlled and targeted release of bioactive agents in tissue engineering applications. In this paper, an overview of the different types of scaffolds with their material properties is discussed. The fabrication technologies for tissue engineering scaffolds, including the basic and conventional techniques to the more recent ones, are tabulated.

1,480 citations

Journal ArticleDOI
TL;DR: In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described.
Abstract: 3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described. Examples are highlighted to illustrate progress of each technology in tissue engineering, and key limitations are identified to motivate future research and advance this fascinating field of advanced manufacturing.

1,288 citations

Journal ArticleDOI
TL;DR: The induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds is described.
Abstract: One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.

1,227 citations