Advances in tissue engineering of vasculature through three-dimensional bioprinting.

BACKGROUND: A significant challenge facing tissue engineering is the fabrication of vasculature constructs which contains vascularized tissue constructs to recapitulate viable, complex and functional organs or tissues, and free-standing vascular structures potentially providing clinical applications in the future. Three-dimensional (3D) bioprinting has emerged as a promising technology, possessing a number of merits that other conventional biofabrication methods do not have. Over the last decade, 3D bioprinting has contributed a variety of techniques and strategies to generate both vascularized tissue constructs and free-standing vascular structures. RESULTS: This review focuses on different strategies to print two kinds of vasculature constructs, namely vascularized tissue constructs and vessel-like tubular structures, highlighting the feasibility and shortcoming of the current methods for vasculature constructs fabrication. Generally, both direct printing and indirect printing can be employed in vascularized tissue engineering. Direct printing allows for structural fabrication with synchronous cell seeding, while indirect printing is more effective in generating complex architecture. During the fabrication process, 3D bioprinting techniques including extrusion bioprinting, inkjet bioprinting and light-assisted bioprinting should be selectively implemented to exert advantages and obtain the desirable tissue structure. Also, appropriate cells and biomaterials matter a lot to match various bioprinting techniques and thus achieve successful fabrication of specific vasculature constructs. CONCLUSION: The 3D bioprinting has been developed to help provide various fabrication techniques, devoting to producing structurally stable, physiologically relevant, and biologically appealing constructs. However, although the optimization of biomaterials and innovation of printing strategies may improve the fabricated vessel-like structures, 3D bioprinting is still in the infant period and has a great gap between in vitro trials and in vivo applications. The article reviews the present achievement of 3D bioprinting in generating vasculature constructs and also provides perspectives on future directions of advanced vasculature constructs fabrication.

Progress in cardiovascular bioprinting.

Cardiovascular disease has been the leading cause of death globally for the past 15 years. Following a major cardiac disease episode, the ideal treatment would be the replacement of the damaged tissue, due to the limited regenerative capacity of cardiac tissues. However, we suffer from a chronic organ donor shortage which causes approximately 20 people to die each day waiting to receive an organ. Bioprinting of tissues and organs can potentially alleviate this burden by fabricating low cost tissue and organ replacements for cardiac patients. Clinical adoption of bioprinting in cardiovascular medicine is currently limited by the lack of systematic demonstration of its effectiveness, high costs, and the complexity of the workflow. Here, we give a concise review of progress in cardiovascular bioprinting and its components. We further discuss the challenges and future prospects of cardiovascular bioprinting in clinical applications.

Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems.

Recent advances in developmental biology and stem cell biology have led to the increased availability of extrarenal stem cells, including mesenchymal/stromal stem cells (MSCs), renal stem or progenitor cells isolated from embryonic and adult kidneys, and kidney lineage cells or tissues generated from human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human-induced pluripotent stem cells. Regenerative medicine strategies for kidney diseases are largely categorized into the transplantation of reconstructed kidney organs and cell therapies. Reconstruction is being attempted by hPSC-derived kidney lineage cells with various strategies, such as self-organization, interspecies blastocyst complementation, utilization of a xenogeneic organ niche, decellularization and repopulation, and 3D bioprinting. However, cell therapies using extrarenal stem cells, such as MSCs, and renal stem or progenitor cells derived from embryonic and adult kidneys or differentiated from hPSCs have been investigated in animal models of both acute kidney injury and chronic kidney disease. Indeed, multiple clinical trials using MSCs, bone marrow stem cells, and kidney-derived cells have already been carried out. This review summarizes the current status and future perspective of kidney regenerative medicine strategies and discusses the closest and fastest strategies to solving the medical and economic problems associated with kidney diseases.

3D Bioprinting of Human Tissues: Biofabrication, Bioinks, and Bioreactors.

The field of tissue engineering has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes for regenerative medicine and pharmaceutical research. Conventional scaffold-based approaches are limited in their capacity to produce constructs with the functionality and complexity of native tissue. Three-dimensional (3D) bioprinting offers exciting prospects for scaffolds fabrication, as it allows precise placement of cells, biochemical factors, and biomaterials in a layer-by-layer process. Compared with traditional scaffold fabrication approaches, 3D bioprinting is better to mimic the complex microstructures of biological tissues and accurately control the distribution of cells. Here, we describe recent technological advances in bio-fabrication focusing on 3D bioprinting processes for tissue engineering from data processing to bioprinting, mainly inkjet, laser, and extrusion-based technique. We then review the associated bioink formulation for 3D bioprinting of human tissues, including biomaterials, cells, and growth factors selection. The key bioink properties for successful bioprinting of human tissue were summarized. After bioprinting, the cells are generally devoid of any exposure to fluid mechanical cues, such as fluid shear stress, tension, and compression, which are crucial for tissue development and function in health and disease. The bioreactor can serve as a simulator to aid in the development of engineering human tissues from in vitro maturation of 3D cell-laden scaffolds. We then describe some of the most common bioreactors found in the engineering of several functional tissues, such as bone, cartilage, and cardiovascular applications. In the end, we conclude with a brief insight into present limitations and future developments on the application of 3D bioprinting and bioreactor systems for engineering human tissue.

A Review of 3-Dimensional Skin Bioprinting Techniques: Applications, Approaches, and Trends.

BACKGROUND: Tissue engineering is used to fabricate 3-dimensional (3D) artificial scaffolds to create a microenvironment that mimics human tissue. Bioprinting uses biomaterials, cells, and/or bioink to fabricate prospective scaffolds to mirror the structural, compositional, and functional aspects of the skin. Various bioprinting methods (inkjet-based bioprinting, pressure-assisted bioprinting, and laser-assisted bioprinting) have been used for regenerative wound repair and have been characterized based on biocompatibility, cellular microenvironment, cell proliferation, vitality, and morphology. OBJECTIVE: This article reviews the basic principles of 3D printing, current 3D skin bioprinting applications and approaches, and future directions for regenerative medical skin constructs. METHODS: A comprehensive literature review was conducted using PubMed with keywords "three-dimensional printing," "dermatologic surgery," "bioprinting," "reconstructive surgical procedures," "wound healing," "skin grafts," "skin scaffolds," "tissue reconstruction," and "tissue engineering." RESULTS: A summary of the different applications and 3-dimensional skin bioprinting techniques is presented. In addition, synthetic, natural, and combination polymers are reviewed. Advantages, disadvantages, indications, and approaches are discussed in depth. CONCLUSION: Skin grafting is a dynamic technique of dermal reconstruction that can be successful with comprehensive knowledge of skin bioprinting methods.

[The application and prospects of three dimensional bioprinting in urinary system reconstruction].

Three dimensional (3D) bioprinting is a new biological tissue engineering technology in recent years. The development of 3D bioprinting is conducive to solving the current problems of clinical tissue and organ repairing. This article provides a review about the clinical and research status of 3D bioprinting and urinary system reconstruction. Furthermore, the feasibility and clinical value of 3D bioprinting in urinary system reconstruction will be also discussed.

Progress in scaffold-free bioprinting for cardiovascular medicine.

Biofabrication of tissue analogues is aspiring to become a disruptive technology capable to solve standing biomedical problems, from generation of improved tissue models for drug testing to alleviation of the shortage of organs for transplantation. Arguably, the most powerful tool of this revolution is bioprinting, understood as the assembling of cells with biomaterials in three-dimensional structures. It is less appreciated, however, that bioprinting is not a uniform methodology, but comprises a variety of approaches. These can be broadly classified in two categories, based on the use or not of supporting biomaterials (known as "scaffolds," usually printable hydrogels also called "bioinks"). Importantly, several limitations of scaffold-dependent bioprinting can be avoided by the "scaffold-free" methods. In this overview, we comparatively present these approaches and highlight the rapidly evolving scaffold-free bioprinting, as applied to cardiovascular tissue engineering.

Recent advances in bioprinting techniques: approaches, applications and future prospects.

Bioprinting technology shows potential in tissue engineering for the fabrication of scaffolds, cells, tissues and organs reproducibly and with high accuracy. Bioprinting technologies are mainly divided into three categories, inkjet-based bioprinting, pressure-assisted bioprinting and laser-assisted bioprinting, based on their underlying printing principles. These various printing technologies have their advantages and limitations. Bioprinting utilizes biomaterials, cells or cell factors as a "bioink" to fabricate prospective tissue structures. Biomaterial parameters such as biocompatibility, cell viability and the cellular microenvironment strongly influence the printed product. Various printing technologies have been investigated, and great progress has been made in printing various types of tissue, including vasculature, heart, bone, cartilage, skin and liver. This review introduces basic principles and key aspects of some frequently used printing technologies. We focus on recent advances in three-dimensional printing applications, current challenges and future directions.

[Possibilities and prospects of three-dimensional bioprinting in vascular surgery].

Rapid development of tissue engineering is gradually changing the approach to patient care. Despite the fact that the use of an autograft or transplantation of an artificial prosthesis is preferred in most cases, this is frequently impossible due to shortage of suitable material or the patient's condition. Regenerative medicine and tissue engineering make it possible to reduce the terms of treatment and restoration after vascular operations, as well as complications rate. At the present moment there is a lot of information about methods of biofabrication and multiple techniques of using stem cells. Nevertheless, clinical efficacy of these methods requires further detailed examination. The review of literature contains the data concerning modern achievements in the area of bioprinting.

Applications of three-dimensional printing technology in urological practice.

A rapid expansion in the medical applications of three-dimensional (3D)-printing technology has been seen in recent years. This technology is capable of manufacturing low-cost and customisable surgical devices, 3D models for use in preoperative planning and surgical education, and fabricated biomaterials. While several studies have suggested 3D printers may be a useful and cost-effective tool in urological practice, few studies are available that clearly demonstrate the clinical benefit of 3D-printed materials. Nevertheless, 3D-printing technology continues to advance rapidly and promises to play an increasingly larger role in the field of urology. Herein, we review the current urological applications of 3D printing and discuss the potential impact of 3D-printing technology on the future of urological practice.

Application of 3D bioprinting in the prevention and the therapy for human diseases.

Rapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.

3D bioprinting in cardiac tissue engineering.

Heart disease is the main cause of death worldwide. Because death of the myocardium is irreversible, it remains a significant clinical challenge to rescue myocardial deficiency. Cardiac tissue engineering (CTE) is a promising strategy for repairing heart defects and offers platforms for studying cardiac tissue. Numerous achievements have been made in CTE in the past decades based on various advanced engineering approaches. 3D bioprinting has attracted much attention due to its ability to integrate multiple cells within printed scaffolds with complex 3D structures, and many advancements in bioprinted CTE have been reported recently. Herein, we review the recent progress in 3D bioprinting for CTE. After a brief overview of CTE with conventional methods, the current 3D printing strategies are discussed. Bioink formulations based on various biomaterials are introduced, and strategies utilizing composite bioinks are further discussed. Moreover, several applications including heart patches, tissue-engineered cardiac muscle, and other bionic structures created via 3D bioprinting are summarized. Finally, we discuss several crucial challenges and present our perspective on 3D bioprinting techniques in the field of CTE.

Three-Dimensional Bioprinting in Orthopaedics.

Three-dimensional (3D)-printing technology has evolved dramatically in the last 30 years, from large machines with poor resolution to those with micron-level capabilities that sit on a desktop. This technology is being utilized in numerous medical applications, particularly in orthopaedic surgery. Over the past decade, technological advances have allowed for the application of this technology to the field of tissue engineering through the process of 3D bioprinting. Of interest to orthopaedic surgeons, active areas of research utilizing this technology involve the bioprinting of articular cartilage, bone, menisci, and intervertebral discs.

Multitechnology Biofabrication: A New Approach for the Manufacturing of Functional Tissue Structures?

Most available 3D biofabrication technologies rely on single-component deposition methods, such as inkjet, extrusion, or light-assisted printing. It is unlikely that any of these technologies used individually would be able to replicate the complexity and functionality of living tissues. Recently, new biofabrication approaches have emerged that integrate multiple manufacturing technologies into a single biofabrication platform. This has led to fabricated structures with improved functionality. In this review, we provide a comprehensive overview of recent advances in the integration of different manufacturing technologies with the aim to fabricate more functional tissue structures. We provide our vision on the future of additive manufacturing (AM) technology, digital design, and the use of artificial intelligence (AI) in the field of biofabrication.

Intraoperative Bioprinting: Repairing Tissues and Organs in a Surgical Setting.

3D bioprinting directly into injured sites in a surgical setting, intraoperative bioprinting (IOB), is an effective process, in which the defect information can be rapidly acquired and then repaired via bioprinting on a live subject. In patients needing tissue resection, debridement, traumatic reconstruction, or fracture repair, the ability to scan and bioprint immediately following surgical preparation of the defect site has great potential to improve the precision and efficiency of these procedures. In this opinion article, we provide the reader with current major limitations of IOB from engineering and clinical points of view, as well as possibilities of future translation of bioprinting technologies from bench to bedside, and expound our perspectives in the context of IOB of composite and vascularized tissues.

The bioprinting roadmap.

This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field.

3D Printing in Suspension Baths: Keeping the Promises of Bioprinting Afloat.

Extrusion-based 3D printers have been adopted in pursuit of engineering functional tissues through 3D bioprinting. However, we are still a long way from the promise of fabricating constructs approaching the complexity and function of native tissues. A major challenge is presented by the competing requirements of biomimicry and manufacturability. This opinion article discusses 3D printing in suspension baths as a novel strategy capable of disrupting the current bioprinting landscape. Suspension baths provide a semisolid medium to print into, voiding many of the inherent flaws of printing onto a flat surface in air. We review the state-of-the-art of this approach and extrapolate toward future possibilities that this technology might bring, including the fabrication of vascularized tissue constructs.