3D Bioprinting Applications Research Articles

Stepwise Multi-Cross-Linking Bioink for 3D Embedded Bioprinting to Promote Full-Thickness Wound Healing.

The emergence and innovation of three-dimensional (3D) bioprinting provide new development opportunities for tissue engineering and regenerative medicine. However, how to obtain bioinks with both biomimicry and manufacturability remains a great issue in 3D bioprinting. Developing intelligent responsive biomaterials is conducive to break through the current dilemma. Herein, a stepwise multi-cross-linking strategy concerning thermosensitive thiolated Pluronic F127 (PF127-SH) and hyaluronic acid methacrylate (HAMA) is proposed to achieve temperature-controlled 3D embedded bioprinting, specifically pre-cross-linking (Michael addition reaction) at low temperatures (4-20 °C) and subsequently self-assembly (hydrophobic interaction) in a high-temperature (30-37 °C) suspension bath as well as final photo-cross-linking (mainly thiol-ene "click" reaction). The unique stepwise cross-linking mechanism promises the thermosensitive bioink appropriate viscosity at different printing stages, making it possible to print complex structures with excellent shape fidelity and simultaneously maintain the biological activity of cells. In vitro studies reveal that 3D-printed hydrogels are beneficial for enhancing cell viability. Further, in vivo experiments demonstrate that cell-laden printed hydrogels significantly promote wound healing and re-epithelialization by modulating inflammation and accelerating collagen deposition and angiogenesis. Therefore, the proposed stepwise multi-cross-linking strategy is expected to accelerate the development of novel bioinks and promote the clinical applications of 3D bioprinting.

Recent advances of three-dimensional bioprinting technology in hepato-pancreato-biliary cancer models.

Hepato-pancreato-biliary (HPB) cancer is a serious category of cancer including tumors originating in the liver, pancreas, gallbladder and biliary ducts. It is limited by two-dimensional (2D) cell culture models for studying its complicated tumor microenvironment including diverse contents and dynamic nature. Recently developed three-dimensional (3D) bioprinting is a state-of-the-art technology for fabrication of biological constructs through layer-by-layer deposition of bioinks in a spatially defined manner, which is computer-aided and designed to generate viable 3D constructs. 3D bioprinting has the potential to more closely recapitulate the tumor microenvironment, dynamic and complex cell-cell and cell-matrix interactions compared to the current methods, which benefits from its precise definition of positioning of various cell types and perfusing network in a high-throughput manner. In this review, we introduce and compare multiple types of 3D bioprinting methodologies for HPB cancer and other digestive tumors. We discuss the progress and application of 3D bioprinting in HPB and gastrointestinal cancers, focusing on tumor model manufacturing. We also highlight the current challenges regarding clinical translation of 3D bioprinting and bioinks in the field of digestive tumor research. Finally, we suggest valuable perspectives for this advanced technology, including combination of 3D bioprinting with microfluidics and application of 3D bioprinting in the field of tumor immunology.

3D Bioprinting for Tumor Metastasis Research.

Tumor metastasis is a multiple cascade process where tumor cells disseminate from the primary site to distant organs and subsequently adapt to the foreign microenvironment. Simulating the physiology of tumor metastatic events in a realistic and three-dimensional (3D) manner is a challenge for in vitro modeling. 3D bioprinting strategies, which can generate well-customized and bionic structures, enable the exploration of dynamic tumor metastasis process in a species-homologous, high-throughput and reproducible way. In this review, we summarize the recent application of 3D bioprinting in constructing in vitro tumor metastatic models and discuss its advantages and current limitations. Further perspectives on how to harness the potential of accessible 3D bioprinting strategies to better model tumor metastasis and guide anti-cancer therapies are also provided.

Deciphering dermal fibroblast behavior in 3D bioprinted dermis constructs

In recent years, numerous strategies have emerged to answer the growing demand for graftable tissues. Tissue engineering and in-vitro production are one of them. Among all the engineered tissues, skin is one of the most advanced. Nevertheless, biofabrication of graftable and fully functional skin substitutes is still far from being reached. Skin reconstruction, particularly dermis, necessitates cultivation and maturation for several weeks (>3 weeks) to recover the tissue's composition and functions, which prevent its transfer to clinical applications. Thus, several strategies, including 3D bioprinting, have been explored to accelerate these productions. In the present study, based on the successful application of 3D bioprinting achieved by our group for skin reconstruction in 21 days, we propose to detail the biological behaviors and maturation phases occurring in the bioprinted skin construct thanks to a descriptive approach transferred from the bioprocess field. The aim is to comprehensively characterize dermis construct maturation phases (cell proliferation and ECM secretion) to master later the interdependent and consecutive mechanisms involved in in-vitro production. Thus, standardized quantitative techniques were deployed to describe 3D bioprinted dermis proliferation and maturation phases. Then, in a second step, various parameters potentially impacting the dermis reconstruction phases were evaluated to challenge our methodology and reveal the biological behavior described (fibroblast proliferation and migration, cell death, ECM remodeling with MMP secretion). The parameters studied concern the bioprinting practice including various printed geometries, bioink formulations and cellular physiology in relation with their nutritional supplementation with selected medium additives.

Bioprinting and biomaterials for dental alveolar tissue regeneration.

Three dimensional (3D) bioprinting is a powerful tool, that was recently applied to tissue engineering. This technique allows the precise deposition of cells encapsulated in supportive bioinks to fabricate complex scaffolds, which are used to repair targeted tissues. Here, we review the recent developments in the application of 3D bioprinting to dental tissue engineering. These tissues, including teeth, periodontal ligament, alveolar bones, and dental pulp, present cell types and mechanical properties with great heterogeneity, which is challenging to reproduce in vitro. After highlighting the different bioprinting methods used in regenerative dentistry, we reviewed the great variety of bioink formulations and their effects on cells, which have been established to support the development of these tissues. We discussed the different advances achieved in the fabrication of each dental tissue to provide an overview of the current state of the methods. We conclude with the remaining challenges and future needs.

Functionalized gelatin-alginate based bioink with enhanced manufacturability and biomimicry for accelerating wound healing

Three-dimensional (3D) bioprinting is a promising technique to construct heterogeneous architectures that mimic cell microenvironment. However, the current bioinks for 3D bioprinting usually show some limitations, such as low printing accuracy, unsatisfactory mechanical properties and compromised cytocompatibility. Herein, a novel bioink comprising hydroxyphenyl propionic acid-conjugated gelatin and tyramine-modified alginate is developed for printing 3D constructs. The bioink takes advantage of an ionic/covalent intertwined network that combines covalent bonds formed by photo-mediated redox reaction and ionic bonds formed by chelate effect. Benefiting from the thermosensitivity of gelatin and the double-crosslinking mechanism, the developed bioink shows controllable rheological behaviors, enhanced mechanical behavior, improved printing accuracy and structure stability. Moreover, the printed cell-laden hydrogels exhibit a homogeneous cell distribution and considerable cell survival because the pre-crosslinking of the bioink prevents cellular sedimentation and the visible light crosslinking mechanism preserves cell viability. Further in vivo studies demonstrate that resulting cell-laden hydrogels are beneficial for the reduction of inflammation response and the promotion of collagen deposition and angiogenesis, thereby improving the quality of skin wound healing. This convenient and effective strategy is of great significance for accelerating the development of multifunctional bioinks and broadening the biomedical applications of 3D bioprinting.

3D Bioprinting in Otolaryngology: A Review.

The evolution of tissue engineering and 3D bioprinting has allowed for increased opportunities to generate musculoskeletal tissue grafts that can enhance functional and aesthetic outcomes in otolaryngology-head and neck surgery. Despite literature reporting successes in the fabrication of cartilage and bone scaffolds for applications in the head and neck, the full potential of this technology has yet to be realized. Otolaryngology as a field has always been at the forefront of new advancements and technology and is well poised to spearhead clinical application of these engineered tissues. In this review, current 3D bioprinting methods are described and an overview of potential cell types, bioinks, and bioactive factors available for musculoskeletal engineering using this technology is presented. The otologic, nasal, tracheal, and craniofacial bone applications of 3D bioprinting with a focus on engineered graft implantation in animal models to highlight the status of functional outcomes in vivo; a necessary step to future clinical translation are reviewed. Continued multidisciplinary efforts between material chemistry, biological sciences, and otolaryngologists will play a key role in the translation of engineered, 3D bioprinted constructs for head and neck surgery.

3D Bioprinting: Manufacturing the Human Heart

Every day, the organ shortage crisis takes away the lives of 17 patients (Health Resources & Services Administration, 2022). The number of patients who require organ transplants significantly exceeds the number of possible donors, and consequently, most patients pass away while waiting for a matching donor organ. To address this issue, 3D bioprinting was suggested as a method by which patients could receive a functioning replica of their own biocompatible organ. This manuscript will cover in depth the materials—the bioink—and the printing methods that are widely used by various researchers in the bioprinting field. More specifically, this manuscript will analyze and compare natural bioinks—alginate and collagen—and synthetic bioinks—Gelatin methacryloyl and polycaprolactone. It will then introduce the two major bioprinting methods—extrusion-based printing and inkjet-based printing—and analyze the advantages and disadvantages of each method. Finally, the manuscript will highlight the successful applications of 3D bioprinting in cardiology using the aforementioned bioinks and printing methods.

(Bio)printing in Personalized Medicine-Opportunities and Potential Benefits.

The global development of technologies now enters areas related to human health, with a transition from conventional to personalized medicine that is based to a significant extent on (bio)printing. The goal of this article is to review some of the published scientific literature and to highlight the importance and potential benefits of using 3D (bio)printing techniques in contemporary personalized medicine and also to offer future perspectives in this research field. The article is prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, PubMed, Scopus, Google Scholar, and ScienceDirect databases were used in the literature search. Six authors independently performed the search, study selection, and data extraction. This review focuses on 3D bio(printing) in personalized medicine and provides a classification of 3D bio(printing) benefits in several categories: overcoming the shortage of organs for transplantation, elimination of problems due to the difference between sexes in organ transplantation, reducing the cases of rejection of transplanted organs, enhancing the survival of patients with transplantation, drug research and development, elimination of genetic/congenital defects in tissues and organs, and surgery planning and medical training for young doctors. In particular, we highlight the benefits of each 3D bio(printing) applications included along with the associated scientific reports from recent literature. In addition, we present an overview of some of the challenges that need to be overcome in the applications of 3D bioprinting in personalized medicine. The reviewed articles lead to the conclusion that bioprinting may be adopted as a revolution in the development of personalized, medicine and it has a huge potential in the near future to become a gold standard in future healthcare in the world.

3D bioprinting tumor models mimic the tumor microenvironment for drug screening.

Cancer is a severe threat to human life and health and represents the main cause of death globally. Drug therapy is one of the primary means of treating cancer; however, most anticancer medications do not proceed beyond preclinical testing because the conditions of actual human tumors are not effectively mimicked by traditional tumor models. Hence, bionic in vitro tumor models must be developed to screen for anticancer drugs. Three-dimensional (3D) bioprinting technology can produce structures with built-in spatial and chemical complexity and models with accurately controlled structures, a homogeneous size and morphology, less variation across batches, and a more realistic tumor microenvironment (TME). This technology can also rapidly produce such models for high-throughput anticancer medication testing. This review describes 3D bioprinting methods, the use of bioinks in tumor models, and in vitro tumor model design strategies for building complex tumor microenvironment features using biological 3D printing technology. Moreover, the application of 3D bioprinting in vitro tumor models in drug screening is also discussed.

Three-Dimensional Digital Light-Processing Bioprinting Using Silk Fibroin-Based Bio-Ink: Recent Advancements in Biomedical Applications.

Three-dimensional (3D) bioprinting has been developed as a viable method for fabricating functional tissues and organs by precisely spatially arranging biomaterials, cells, and biochemical components in a layer-by-layer fashion. Among the various bioprinting strategies, digital light-processing (DLP) printing has gained enormous attention due to its applications in tissue engineering and biomedical fields. It allows for high spatial resolution and the rapid printing of complex structures. Although bio-ink is a critical aspect of 3D bioprinting, only a few bio-inks have been used for DLP bioprinting in contrast to the number of bio-inks employed for other bioprinters. Recently, silk fibroin (SF), as a natural bio-ink material used for DLP 3D bioprinting, has gained extensive attention with respect to biomedical applications due to its biocompatibility and mechanical properties. This review introduces DLP-based 3D bioprinting, its related technology, and the fabrication process of silk fibroin-based bio-ink. Then, we summarize the applications of DLP 3D bioprinting based on SF-based bio-ink in the tissue engineering and biomedical fields. We also discuss the current limitations and future perspectives of DLP 3D bioprinting using SF-based bio-ink.

Bioprinting on Organ-on-Chip: Development and Applications.

Organs-on-chips (OoCs) are microfluidic devices that contain bioengineered tissues or parts of natural tissues or organs and can mimic the crucial structures and functions of living organisms. They are designed to control and maintain the cell- and tissue-specific microenvironment while also providing detailed feedback about the activities that are taking place. Bioprinting is an emerging technology for constructing artificial tissues or organ constructs by combining state-of-the-art 3D printing methods with biomaterials. The utilization of 3D bioprinting and cells patterning in OoC technologies reinforces the creation of more complex structures that can imitate the functions of a living organism in a more precise way. Here, we summarize the current 3D bioprinting techniques and we focus on the advantages of 3D bioprinting compared to traditional cell seeding in addition to the methods, materials, and applications of 3D bioprinting in the development of OoC microsystems.

3D Gelatin Microsphere Scaffolds Promote Functional Recovery after Spinal Cord Hemisection in Rats.

Spinal cord injury (SCI) damages signal connections and conductions, with the result that neuronal circuits are disrupted leading to neural dysfunctions. Such injuries represent a serious and relatively common central nervous system condition and current treatments have limited success in the reconstruction of nerve connections in injured areas, especially where sizeable gaps are present. Biomaterial scaffolds have become an effective alternative to nerve transplantation in filling these gaps and provide the foundation for simulating the 3D structure of solid organs. However, there remain some limitations with the application of 3D bioprinting for preparation of biomaterial scaffolds. Here, the approach in constructing and testing mini-tissue building blocks and self-assembly, solid 3D gelatin microsphere (GM) scaffolds with multiple voids as based on the convenient preparation of gelatin microspheres by microfluidic devices is described. These 3D GM scaffolds demonstrate suitable biocompatibility, biodegradation, porosity, low preparation costs, and relative ease of production. Moreover, 3D GM scaffolds can effectively bridge injury gaps, establish nerve connections and signal transductions, mitigate inflammatory microenvironments, and reduce glial scar formation. Accordingly, these 3D GM scaffolds can serve as a novel and effective bridging method to promote nerve regeneration and reconstruction and thus recovery of nerve function after SCI.

Therapeutic Approaches for Age-Related Macular Degeneration.

Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse effects. In the same way, 3D bioprinting constitutes an alternative to regeneration therapies for the human retina to restore its functions. The application of 3D bioprinting may change the current and future perspectives of the treatment of patients with AMD, especially those who do not respond to conventional treatment. To monitor the progress of AMD treatment and disease, retinal images are used. In this work, we revised the recent challenges encountered in the treatment of different forms of AMD, innovative nanoformulations, 3D bioprinting, and techniques to monitor the progress.

Three-dimensional bioprinting: A cutting-edge tool for designing and fabricating engineered living materials.

The design of engineered living materials (ELMs) is an emerging field developed from synthetic biology and materials science principles. ELMs are multi-scale bulk materials that combine the properties of self-healing and organism adaptability with the designed physicochemical or mechanical properties for functional applications in various fields, including therapy, electronics, and architecture. Among the many ELM design and manufacturing methods, three-dimensional (3D) bioprinting stands out for its precise control over the structure of the fabricated constructs and the spatial distribution of cells. In this review, we summarize the progress in the field, cell type and material selection, and the latest applications of 3D bioprinting to manufacture ELMs, as well as their advantages and limitations, hoping to deepen our understanding and provide new insights into ELM design. We believe that 3D bioprinting will become an important development direction and provide more contributions to this field.

The application of 3D bioprinting in urological diseases.

Urologic diseases are commonly diagnosed health problems affecting people around the world. More than 26 million people suffer from urologic diseases and the annual expenditure was more than 11 billion US dollars. The urologic cancers, like bladder cancer, prostate cancer and kidney cancer are always the leading causes of death worldwide, which account for approximately 22% and 10% of the new cancer cases and death, respectively. Organ transplantation is one of the major clinical treatments for urological diseases like end-stage renal disease and urethral stricture, albeit strongly limited by the availability of matching donor organs. Tissue engineering has been recognized as a highly promising strategy to solve the problems of organ donor shortage by the fabrication of artificial organs/tissue. This includes the prospective technology of three-dimensional (3D) bioprinting, which has been adapted to various cell types and biomaterials to replicate the heterogeneity of urological organs for the investigation of organ transplantation and disease progression. This review discusses various types of 3D bioprinting methodologies and commonly used biomaterials for urological diseases. The literature shows that advances in this field toward the development of functional urological organs or disease models have progressively increased. Although numerous challenges still need to be tackled, like the technical difficulties of replicating the heterogeneity of urologic organs and the limited biomaterial choices to recapitulate the complicated extracellular matrix components, it has been proved by numerous studies that 3D bioprinting has the potential to fabricate functional urological organs for clinical transplantation and in vitro disease models.

Application of 3D Bioprinting in Urology.

Tissue engineering is an emerging field to create functional tissue components and whole organs. The structural and functional defects caused by congenital malformation, trauma, inflammation or tumor are still the major clinical challenges facing modern urology, and the current treatment has not achieved the expected results. Recently, 3D bioprinting has gained attention for its ability to create highly specialized tissue models using biological materials, bridging the gap between artificially engineered and natural tissue structures. This paper reviews the research progress, application prospects and current challenges of 3D bioprinting in urology tissue engineering.

3D bioprinting technology and its latest application in ophthalmology

<p indent="0mm">3D bio-printing technology is an emerging technology in recent years, which is driven by digital three-dimensional model and based on a certain additive manufacturing principle, positioning and assembling biological materials and cell units to form medical devices, engineered tissues, artificial organs and other products. Its emergence may solve the shortage of organs for transplant and thus prolong the life of patients or improve their quality of life. In the field of ophthalmology, it is expected to construct eyeball refractive system components through “bio-printing”, which has great development prospects in the field of ophthalmology. This paper briefly introduces 3D bioprinting technology and its latest application in ophthalmology. We will report the current research progress and future development trend, aiming to improve the understanding of ophthalmology doctors and related fields on 3D bioprinting in the application of ophthalmology, so as to accelerate the development and application of 3D bioprinting.

Avant-garde Approach to Life: Reviewing the Current Applications of 3D Bioprinting

Introduction: The promise of bioprinting tissue constructs that could potentially serve the same function in the human body as native tissues has taken the world of regenerative medicine by storm. The current review describes system-wide clinical applications of three-dimensional (3D) bioprinting and aims to address ethical and social considerations, while also discussing the scope of this technology in the near future. Discussion: 3D bioprinting is believed to present new approaches to conventional treatment, offering the advantage of customization and on-time availability. It facilitates simultaneous deposition of appropriate bioinks and biomaterials onto scaffolds which can then be employed to develop tissue fabricates that can potentially mimic native tissues in both structure and functionality. It has been extensively employed to regenerate viable tissue constructs of skin, bone, cartilage, vasculature, myocardial tissue and heart valves, nervous tissue, lung and tracheal tissue, liver, pancreatic, and corneal tissue. Conclusion: To obviate the current restrictions associated with this technology, it is imperative to understand where we currently stand in terms of current clinical applications of 3D bioprinting. This technology is anticipated to contribute significantly to the fields of tissue engineering and regenerative medicine (TERM), where it can be employed to fabricate functional tissues that can simulate their counterparts in the human body. Relevance: The increasing disparity between organ demand and supply as well as the shortcomings associated with antiquated approaches to treatment call for utilizing 3D bioprinting to develop viable tissue constructs.

Avant-garde Approach to Life: Reviewing the Current Applications of 3D Bioprinting

Introduction: The promise of bioprinting tissue constructs that could potentially serve the same function in the human body as native tissues has taken the world of regenerative medicine by storm. The current review describes system-wide clinical applications of three-dimensional (3D) bioprinting and aims to address ethical and social considerations, while also discussing the scope of this technology in the near future. Discussion: 3D bioprinting is believed to present new approaches to conventional treatment, offering the advantage of customization and on-time availability. It facilitates simultaneous deposition of appropriate bioinks and biomaterials onto scaffolds which can then be employed to develop tissue fabricates that can potentially mimic native tissues in both structure and functionality. It has been extensively employed to regenerate viable tissue constructs of skin, bone, cartilage, vasculature, myocardial tissue and heart valves, nervous tissue, lung and tracheal tissue, liver, pancreatic, and corneal tissue. Conclusion: To obviate the current restrictions associated with this technology, it is imperative to understand where we currently stand in terms of current clinical applications of 3D bioprinting. This technology is anticipated to contribute significantly to the fields of tissue engineering and regenerative medicine (TERM), where it can be employed to fabricate functional tissues that can simulate their counterparts in the human body. Relevance: The increasing disparity between organ demand and supply as well as the shortcomings associated with antiquated approaches to treatment call for utilizing 3D bioprinting to develop viable tissue constructs.