Development Of 3D Bioprinting Research Articles

Recent advances in the development of bioartificial pancreas using 3D bioprinting for the treatment of type 1 diabetes: a review

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, recent developments in 3D bioprinting of endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations have been discussed in detail. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

Recent Developments in 3D Bio-Printing and Its Biomedical Applications.

The fast-developing field of 3D bio-printing has been extensively used to improve the usability and performance of scaffolds filled with cells. Over the last few decades, a variety of tissues and organs including skin, blood vessels, and hearts, etc., have all been produced in large quantities via 3D bio-printing. These tissues and organs are not only able to serve as building blocks for the ultimate goal of repair and regeneration, but they can also be utilized as in vitro models for pharmacokinetics, drug screening, and other purposes. To further 3D-printing uses in tissue engineering, research on novel, suitable biomaterials with quick cross-linking capabilities is a prerequisite. A wider variety of acceptable 3D-printed materials are still needed, as well as better printing resolution (particularly at the nanoscale range), speed, and biomaterial compatibility. The aim of this study is to provide expertise in the most prevalent and new biomaterials used in 3D bio-printing as well as an introduction to the associated approaches that are frequently considered by researchers. Furthermore, an effort has been made to convey the most pertinent implementations of 3D bio-printing processes, such as tissue regeneration, etc., by providing the most significant research together with a comprehensive list of material selection guidelines, constraints, and future prospects.

Development and Characterization of Complementary Polymer Network Bioinks for 3D Bioprinting of Soft Tissue Constructs.

The development of 3D bioprinting has been hindered by a narrow "biofabrication window" with a limited variety of feasible bioinks which are compatible with both high printability and well cytocompatibility. Herein, a generalizable strategy using complementary polymer network (CPN) bioinks is developed in the current study, to address the conflict between the printability and cytocompatibility of bioinks in extrusion 3D bioprinting, especially for the manufacture of soft tissue constructs. In this strategy, CPN bioinks are formed though mixing two interpenetrated polymer networks, one of which is a photocrosslinkable polymer network, and the other is a dynamic polymer network crosslinked by reversible covalent linkage, thereby endowed with well reversible thixotropy. Compatible with well printability, shape fidelity, and cytocompatibility, the utilization of CPN bioinks provides a viable solution for extrusion 3D bioprinting of photocrosslinkable biomaterials at a low concentration, thus suitable for soft tissue construct fabrication. Briefly, this study is testified to be a successful attempt to extend the bioink diversity within the "biofabrication window," and offers a novel insight into designing more feasible bioinks based on their special rheological properties, for further tissue engineering and biomedicine application.

Технология 3D-биопечати: вопросы биоэтики

Scientific development of 3D bioprinting is rapidly advancing. Bioprinting is expected to be actively implemented within the healthcare industry producing a revolutionary impact on transplantation. However, the innovative biotechnology involves numerous ethical and regulatory issues. Special attention is given to ethical issues associated with the use of embryonic cells, storage of personal data, obtaining informed consent, and peculiarities of clinical trials. The issues of safety and quality are reviewed. Equal access to technologies and use of biotechnologies to ‘enhance a human being’ are addressed. The issues of culture and religion are separately discussed within the context of this technology. It is stressed that as far as the issue of ethical estimation and legal regulation goes, 3D bioprinting can’t be completely assessed with the help of regular clinical trials or acting regulatory requirements. In particular, no suitable regulatory system or special documents regulating 3D bioprinting of tissues and organs and their subsequent transplantation are currently available in Russia or globally. Thus, it’s necessary to develop requirements to safety, quality and effectiveness of technological processes and end products obtained with the help of 3D bioprinting with the best interests of generally acknowledged human rights.

Application and development of 3D bioprinting in cartilage tissue engineering.

Articular cartilage defects are one of the most common clinical diseases of bone articulation. Early repair of damaged joint cartilage can effectively stop the progression of arthritis and restore health to the patient. In recent years, various therapeutic strategies have been developed to repair cartilage defects and make them available for clinical transplantation. However, cartilage defect repair remains a clinically unsolved challenge to date. Although there have been numerous breakthroughs in cartilage defect repair, the limited spatial complexity of tissue-engineered implants in terms of cells, materials, and active factors has limited the success of engineered cartilage so far. Bioprinting technology allows for the construction of three-dimensional tissues drop by drop and layer by layer, where cells, matrices, and active materials can be deposited on demand while maintaining high precision. Therefore, adopting the bioprinting technology in cartilage tissue engineering promises to develop the next generation of engineered cartilage and address the cartilage defect/regeneration problem. In this paper, we reviewed the bioinks and bioprinting technologies used in cartilage tissue engineering, outlined the recent advances of 3D bioprinting technologies in cartilage tissue engineering, and prospected the development direction of next-generation engineered cartilage.

3D-bioprinted microenvironments for sweat gland regeneration.

The development of 3D bioprinting in recent years has provided new insights into the creation of in vitro microenvironments for promoting stem cell-based regeneration. Sweat glands (SGs) are mainly responsible for thermoregulation and are a highly differentiated organ with limited regenerative ability. Recent studies have focused on stem cell-based therapies as strategies for repairing SGs after deep dermal injury. In this review, we highlight the recent trend in 3D bioprinted native-like microenvironments and emphasize recent advances in functional SG regeneration using this technology. Furthermore, we discuss five possible regulatory mechanisms in terms of biochemical factors and structural and mechanical cues from 3D bioprinted microenvironments, as well as the most promising regulation from neighbor cells and the vascular microenvironment.

Translational Application of 3D Bioprinting for Cartilage Tissue Engineering.

Cartilage is an avascular tissue with extremely limited self-regeneration capabilities. At present, there are no existing treatments that effectively stop the deterioration of cartilage or reverse its effects; current treatments merely relieve its symptoms and surgical intervention is required when the condition aggravates. Thus, cartilage damage remains an ongoing challenge in orthopaedics with an urgent need for improved treatment options. In recent years, major advances have been made in the development of three-dimensional (3D) bioprinted constructs for cartilage repair applications. 3D bioprinting is an evolutionary additive manufacturing technique that enables the precisely controlled deposition of a combination of biomaterials, cells, and bioactive molecules, collectively known as bioink, layer-by-layer to produce constructs that simulate the structure and function of native cartilage tissue. This review provides an insight into the current developments in 3D bioprinting for cartilage tissue engineering. The bioink and construct properties required for successful application in cartilage repair applications are highlighted. Furthermore, the potential for translation of 3D bioprinted constructs to the clinic is discussed. Overall, 3D bioprinting demonstrates great potential as a novel technique for the fabrication of tissue engineered constructs for cartilage regeneration, with distinct advantages over conventional techniques.

Towards the Experimentally-Informed In Silico Nozzle Design Optimization for Extrusion-Based Bioprinting of Shear-Thinning Hydrogels

Research in bioprinting is booming due to its potential in addressing several manufacturing challenges in regenerative medicine. However, there are still many hurdles to overcome to guarantee cell survival and good printability. For the 3D extrusion-based bioprinting, cell viability is amongst one of the lowest of all the bioprinting techniques and is strongly influenced by various factors including the shear stress in the print nozzle. The goal of this study is to quantify, by means of in silico modeling, the mechanical environment experienced by the bioink during the printing process. Two ubiquitous nozzle shapes, conical and blunted, were considered, as well as three common hydrogels with material properties spanning from almost Newtonian to highly shear-thinning materials following the power-law behavior: Alginate-Gelatin, Alginate and PF127. Comprehensive in silico testing of all combinations of nozzle geometry variations and hydrogels was achieved by combining a design of experiments approach (DoE) with a computational fluid dynamics (CFD) of the printing process, analyzed through a machine learning approach named Gaussian Process. Available experimental results were used to validate the CFD model and justify the use of shear stress as a surrogate for cell survival in this study. The lower and middle nozzle radius, lower nozzle length and the material properties, alone and combined, were identified as the major influencing factors affecting shear stress, and therefore cell viability, during printing. These results were successfully compared with those of reported experiments testing viability for different nozzle geometry parameters under constant flow rate or constant pressure. The in silico 3D bioprinting platform developed in this study offers the potential to assist and accelerate further development of 3D bioprinting.

Current Developments in 3D Bioprinting for Tissue and Organ Regeneration–A Review

The field of Tissue engineering and regenerative medicine that work towards creating functional tissue-constructs mimicking native tissue for repair and/or replacement of damaged tissues or whole organs have evolved rapidly over the past few decades. However, traditional tissue engineering approaches comprising of scaffolds, growth factors and cells showed limited success in fabrication of complex 3D shapes and in vivo organ regeneration leading to their non-feasibility for clinical applications from a logistical and economical viewpoint. In this regard, 3D bioprinting, which is an extended application of additive manufacturing is now being explored for tissue engineering and regenerative medicine as it involves the top-down approach of building the complex tissue in a layer by layer fashion, thereby producing precise geometries due to controlled nature of matter deposition with the help of anatomically accurate 3D models of the tissue generated by computer graphics. Here, we aim to provide a comprehensive review of the 3D bioprinting technology along with associated 3D bioprinting strategies including ink-jet printing, extrusion printing, stereolithography and laser assisted bioprinting techniques. We then focus on the applications of 3D bioprinting technology on construction of various representative tissue and oragans, including skin, cardiac, bone and cartilage etc. We further attempt to highlight the steps involved in each of those tissues/organs printing and discuss on the associated technological requirements based on the available reports from recent literature. We finally conclude with current challenges with 3D bioprinting technology along with potential solution for future technological advancement of efficient and cost-effective 3D bioprinting methods.

Legal and Bioethical Changes in the Commodification of Human, Including Bioprinted, Organs and Tissues

Modern breakthrough scientific ideas in the field of introduction and development of biomedical technologies have led to a significant objectification of the human body. The paper analyzes the trend of commodification of the human body and its parts from the standpoint of bioethics and law, which determines the consideration of these as goods that participate in economic turnover and have their own price. The problems of insufficiency of human organs suitable for transplantation, the risk of rejection of the transplant by the recipient’s immune system, as well as the need to ensure the safety of donor organs and tissues can be leveled by creating artificial human organs and tissues, including through the use of advanced additive technologies (3D bioprinting), creating a three-dimensional model of a human organ on a cellular basis, which is subject to subsequent transplantation to a recipient in need. The development of 3D-bioprinting allows us to resolve bioethical and legal contradictions caused by the actual inclusion of human organs and tissues in civil (economic) turnover, while international acts enshrine the principle of inadmissibility of commercialization of the human body, by virtue of which the human body and its parts should not be a source of financial benefit. The author summarizes that 3D bioprinting is able to significantly smooth out the negative manifestations of the human body commodification trend. The peculiarity of applying the principle of non-commercialization of the human body is due to the fact that in this case the emphasis is placed on obtaining cellular material for creating a bioprinted human organ. First of all, the principle of non-commercialization of the human body should remain in effect when providing cell material by a third party (donor), even if only in terms of determining the legal regime of cell material and created bioprinted human organs and tissues. If the recipient’s own cells are used, this principle loses its meaning.

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.

A three-dimensional model for analysis and control of phase change phenomena during 3D printing of biological tissue

Three-dimensional (3D) bioprinting is one of the fastest advancing and most promising techniques for tissue engineering. However, despite numerous developments in 3D bioprinting, issues of size scalability remain. Two primary factors limiting the scale of printable objects are the structural properties of the bioinks and the unsustainable time it takes to bioprint large structures. Freezing has been proposed as a possible solution to both, improving the mechanical properties of the soft aqueous hydrogel bioinks and reducing the adverse effects of cell metabolism with the lowered temperature. In addition, it eases the longer-term cryopreservation of the larger tissue constructs as they can be frozen element by element at faster (more preferable) and uniform cooling rates during printing rather than whole after 3D bioprinting. However, for freezing to be a feasible 3D bioprinting technique, there is a need to better understand the effect of phase change during printing on biological matter. This can be done by rigorous experimentation or alternatively, using mathematical tools and models. Though, most techniques of 3D printing are inherently thermal processes, limited thermal analysis has been done on extrusion-based (fused deposition modeling) printing processes to characterize thermal effects. This paper introduces a model for analysis of the thermal phase change process during the 3D bioprinting of biological matter at low temperature. The model was developed and experimentally validated for an extrusion-based printing process of aqueous biological material. It was used to investigate the conditions under which a constant freezing rate could be achieved during multilayer printing and the size limitations in conduction dependent freezing from a cold surface during printing. Overall, this model could be a useful tool for the design and control of the 3D printing protocols.

A Brief Review on 3D Bioprinted Skin Substitutes

The global escalating cases of skin donor shortage for patients with severe wounds warn the vital need for alternatives to skin allografts. Over the last three decades, research in the skin regeneration area has addressed the unmet need for artificial skin substitutes. 3D bioprinting is a promising innovative technology to accurately fabricate skin constructs based on natural or synthetic bioinks, whether loaded or not loaded with native skin cells (i.e., keratinocytes and fibroblasts) or stem cells in the prescribed 3D hierarchal structure to create artificial multilayer and single cell-laden construct. In this paper, the recent developments in 3D bioprinting for skin regeneration are reviewed to discuss different aspects of skin bioprinted substitutes, including 3D printing technology, bioink composition, and cell-laden constructs. The impact of 3D printing parameters on functionality of the skin substitute and cell viability is reviewed to provide insight into controlled fabrication as the critical component of advanced wound healing. We highlight the recent and ongoing research in skin bioprinting to address the progress in the translation of advanced wound healing from lab to clinic.

Opportunities and challenges of translational 3D bioprinting.

3D-printed orthopaedic devices and surgical tools, printed maxillofacial implants and other printed acellular devices have been used in patients. By contrast, bioprinted living cellular constructs face considerable translational challenges. In this Perspective, we first summarize the most recent developments in 3D bioprinting for clinical applications, with a focus on how 3D-printed cartilage, bone and skin can be designed for individual patients and fabricated using the patient's own cells. We then discuss key translational considerations, such as the need to ensure close integration of the living device with the patient's vascular network, the development of biocompatible bioinks and the challenges in deriving a physiologically relevant number of cells. Lastly, we outline untested regulatory pathways, as well as logistical challenges in material sourcing, manufacturing, standardization and transportation.

The Adoption of Three-Dimensional Additive Manufacturing from Biomedical Material Design to 3D Organ Printing

Three-dimensional (3D) bioprinting promises to change future lifestyle and the way we think about aging, the field of medicine, and the way clinicians treat ailing patients. In this brief review, we attempt to give a glimpse into how recent developments in 3D bioprinting are going to impact vast research ranging from complex and functional organ transplant to future toxicology studies and printed organ-like 3D spheroids. The techniques were successfully applied to reconstructed complex 3D functional tissue for implantation, application-based high-throughput (HTP) platforms for absorption, distribution, metabolism, and excretion (ADME) profiling to understand the cellular basis of toxicity. We also provide an overview of merits/demerits of various bioprinting techniques and the physicochemical basis of bioink for tissue engineering. We briefly discuss the importance of universal bioink technology, and of time as the fourth dimension. Some examples of bioprinted tissue are shown, followed by a brief discussion on future biomedical applications.

From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases.

In the last decade, the advances made into the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) led to great improvements towards their use as models of diseases. In particular, in the field of neurodegenerative diseases, iPSCs technology allowed to culture in vitro all types of patient-specific neural cells, facilitating not only the investigation of diseases’ etiopathology, but also the testing of new drugs and cell therapies, leading to the innovative concept of personalized medicine. Moreover, iPSCs can be differentiated and organized into 3D organoids, providing a tool which mimics the complexity of the brain’s architecture. Furthermore, recent developments in 3D bioprinting allowed the study of physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bio-plotter and biomaterials in which several types of cells, such as iPSCs or differentiated neurons, can be encapsulated in order to develop an innovative cellular model. IPSCs and 3D cell cultures technologies represent the first step towards the obtainment of a more reliable model, such as organoids, to facilitate neurodegenerative diseases’ investigation. The combination of iPSCs, 3D organoids and bioprinting will also allow the development of new therapeutic approaches. Indeed, on the one hand they will lead to the development of safer and patient-specific drugs testing but, also, they could be developed as cell-therapy for curing neurodegenerative diseases with a regenerative medicine approach.

Research progress on the technique and materials for three-dimensional bio-printing

Three-dimensional (3D) bio-printing is a novel engineering technique by which the cells and support materials can be manufactured to a complex 3D structure. Compared with other 3D printing methods, 3D bio-printing should pay more attention to the biocompatible environment of the printing methods and the materials. Aimed at studying the feature of the 3D bio-printing, this paper mainly focuses on the current research state of 3D bio-printing, with the techniques and materials of the bio-printing especially emphasized. To introduce current printing methods, the inkjet method, extrusion method, stereolithography skill and laser-assisted technique are described. The printing precision, process, requirements and influence of all the techniques on cell status are compared. For introduction of the printing materials, the cross-link, biocompatibility and applications of common bio-printing materials are reviewed and compared. Most of the 3D bio-printing studies are being remained at the experimental stage up to now, so the review of 3D bio-printing could improve this technique for practical use, and it could also contribute to the further development of 3D bio-printing.