Engineering the future of organ transplantation: A comprehensive review of 3D bioprinting advances for organ bioengineering

Organ transplantation is the optimal treatment for patients with end-stage organ failure, but which faces the challenge of donor shortage. Two-dimensional cell culture and animal experiments are difficult to completely simulate the complex cellular microenvironment for drug testing. Three-dimensional (3D) bioprinting is an emerging manufacturing technology to fabricate artificial tissues and organs for transplantation and drug screening. This review first describes the bioprinting technologies used to fabricate constructs, including jetting-based, extrusion-based, vat photopolymerization-based methods and other emerging 3D bioprinting approaches. The various kinds of bioinks, cell sources, and the most recent applications of 3D bioprinting tissues and organs in transplantation and drug testing are subsequently summarized. Finally, we discuss the challenges and prospects of 3D bioprinting of tissues and organs. This review aims to facilitate the overcoming of the obstacles identified on the challenging journey towards the manufacturing and adoption of tissue and organs in transplantation and drug screening.

In the era of personalised medicine, novel therapeutic approaches raise increasing hopes to address currently unmet medical needs by developing patient-customised treatments. Three-dimensional (3D) bioprinting is rapidly evolving and has the potential to obtain personalised tissue constructs and overcome some limitations of standard tissue engineering approaches. Bioprinting could support a wide range of biomedical applications, such as drug testing, tissue repair or organ transplantation. There is a growing interest for 3D bioprinting in the orthopaedic field, with remarkable scientific and technical advances. However, the full exploitation of 3D bioprinting in medical applications still requires efforts to anticipate the upcoming challenges in translating bioprinted products from bench to bedside. In this review we summarised current trends, advances and challenges in the application of 3D bioprinting for bone and cartilage tissue engineering. Moreover, we provided a detailed analysis of the applicable regulations through the 3D bioprinting process and an overview of available standards covering bioprinting and additive manufacturing.

Bone defects are due to trauma, infections, tumors, or aging, including bone fractures, bone metastases, osteoporosis, or osteoarthritis. The global burden of these demands research into innovative strategies that overcome the limitations of conventional autografts. In this sense, the development of three-dimensional (3D) bioprinting has emerged as a promising approach in the field of tissue engineering and regenerative medicine (TERM) for the on-demand generation and transplantation of tissues and organs, including bone. It combines biological materials and living cells, which are precisely positioned layer by layer. Despite obtaining some promising results, 3D bioprinting of bone tissue still faces several challenges, such as generating an effective vascular network to increase tissue viability. In this review, we aim to collect the main knowledge on methods and techniques of 3D bioprinting. Then, we will review the main biomaterials, their composition, and the rationale for their application in 3D bioprinting for the TERM of bone.

The field of three-dimensional (3D) bioprinting is rapidly emerging as an additive manufacturing method for tissue and organ fabrication. The demand for tissues and organ transplants is ever increasing, although donors are not as readily available. Consequently, tissue engineering is gaining much attention to alleviate this problem. The process of achieving well-structured 3D bioprinted constructs using hydrogel bioinks depends on symmetrical precision, regulated flow rates, and viability of cells. Even with the mentioned parameters optimized, the printed structures need additional refining by removing excessive liquids, as peptide hydrogel bioprints encapsulate water. However, it is challenging to eliminate the confined fluids without compromising the printing process. In this paper, we introduced a vacuum system to our 3D bioprinting robotic arm and thus optimized the printing quality for complex and refined 3D scaffolds. Moreover, the proposed vacuum system supports printing with cells. Our results show improved printing resolution which facilitates the printing of higher and more stable structures.

Regenerative medicine holds the promise of engineering functional tissues or organs to heal or replace abnormal and necrotic tissues/organs, offering hope for filling the gap between organ shortage and transplantation needs. Three-dimensional (3D) bioprinting is evolving into an unparalleled biomanufacturing technology due to its high-integration potential for patient-specific designs, precise and rapid manufacturing capabilities with high resolution, and unprecedented versatility. It enables precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity, therefore achieving effective recapitulation of microstructure, architecture, mechanical properties, and biological functions of target tissues and organs. Here we provide an overview of recent advances in 3D bioprinting technology, as well as design concepts of bioinks suitable for the bioprinting process. We focus on the applications of this technology for engineering living organs, focusing more specifically on vasculature, neural networks, the heart and liver. We conclude with current challenges and the technical perspective for further development of 3D organ bioprinting.

The development of additive technologies opens up new opportunities in the healthcare system, revealing its potential in three areas: biopharmaceuticals; biomodeling; 3D printing of human organs and tissues. The law does not have time to respond to the results of a technological breakthrough, while creating some artificial barriers to the implementation of the results of progress in the usual practice of public health. The presence of systemic gaps necessitates monitoring the current situation, identifying problematic aspects that require legal regulation, and identifying the risks of developing new technologies. The universality of the problematic predetermines an appeal to foreign experience (using the method of comparative law) from the point of view of the possibility of its projection in Russian lawmaking practice. The article analyzes Russian legal acts, thanks to which conclusions are presented on the possibilities of general and special regulation of bioprinting. It is proposed to expand the scope of Federal Law No. 258-FZ of July 31, 2020 “On experimental legal regimes in the field of digital innovations in the Russian Federation” to 3D bioprinting. The proposed approach of extending the regime of a medical device to the results of bioprinting — human organs and tissues — is criticized. The necessity of the appearance of special rules reflecting the peculiarities of bioprinting in pharmaceuticals and medicine is substantiated. It is proposed to introduce into the legislation of the Russian Federation the concept of hospital exclusion, which establishes a special legal regime for advanced therapy medicines, including drugs manufactured using additive technologies. The consequences of the introduction of 3D bioprinting into the practice of transplantation of human organs and tissues are shown. This will lead not only to a revision of the Law of the Russian Federation No. 4180-I of December 22, 1992 “On Transplantation of organs and (or) human tissues”, but also to a significant expansion of the regulatory powers of the Ministry of Health of the Russian Federation.

Organ transplantation can serve as a blessing for end-stage organ patients, and issues such as organ shortage and transplantation risks also make research on organ transplantation very important. Nanotechnology involves the development of materials called nanoparticles, which are defined as having a one-dimensional range of at least 1 to 100 nm. This paper introduces the application of nanotechnology in overcoming the drawbacks of traditional medicine, and its nanoscale size has also contributed to organ transplantation. The combination of Magnetic resonance imaging (MRI) and Magnetic hyperthermia (MHT), nanoparticles can better capture transplant medical images, and nanotechnology plays an important role in monitoring treatment responses and designing organ transplantation methods. CRISPR/CAS9 system and Entrancer™ can reduce the role in rejection reactions. Normothermic Machine Perfusion (NMP), protein corona, and curcumin can reduce their effects on ischemia-reperfusion injury. The development of nanomedicine can provide a platform for significant progress in transplant vitality. In future research, nanoparticles can also be applied in 3D bioprinting and artificial intelligence (AI) to better assist in transplant therapy.

The shortage of donor organs remains a critical challenge in modern medicine, with thousands of patients worldwide on transplant waiting lists. 3D bioprinting has emerged as a groundbreaking technology that has the potential to revolutionize organ transplantation by enabling the fabrication of patient-specific tissues and organs. This paper examines the current state of organ transplantation, the challenges associated with donor dependency, and how 3D bioprinting is transforming the field. We discuss the technological advancements in bioprinting, including the development of biomaterials, vascularization techniques, and artificial organ fabrication. Additionally, we analyze ethical and regulatory considerations surrounding bioprinting and its potential societal impact. Looking beyond bioprinting, we examine emerging technologies in regenerative medicine, such as stem cell therapy and gene editing, which may further enhance the future of organ transplants. As bioprinting continues to evolve, it holds the promise of improving transplant success rates, reducing dependency on donors, and ultimately saving countless lives. Keywords: 3D bioprinting, organ transplantation, regenerative medicine, bio-ink, tissue engineering, ethical considerations.

The shortage of organ donors presents a critical challenge in modern healthcare, with demand for organ transplants far outstripping supply. 3D bioprinting, a transformative innovation leveraging biological materials and cells to create tissues and organs, offers a promising solution. This review examines the evolution of 3D bioprinting from early tissue engineering methods to its current role in regenerative medicine and organ transplant applications. It discussed key bioprinting techniques, bio-inks, and scaffold materials that support tissue growth, as well as the technical challenges and ethical considerations faced by researchers. With potential applications ranging from cartilage and skin grafts to fully functional organs, 3D bioprinting stands at the forefront of a new era in organ transplantation. However, barriers such as vascularization, biocompatibility, and regulatory hurdles remain before this technology can be fully integrated into clinical practice. Keywords: 3D bioprinting, organ transplantation, bioink, regenerative medicine, tissue engineering.

Tissue and Organ 3D Bioprinting.

Induced pluripotent stem cell (iPSC) technology and advancements in three-dimensional (3D) bioprinting technology enable scientists to reprogram somatic cells to iPSCs and 3D print iPSC-derived organ constructs with native tissue architecture and function. iPSCs and iPSC-derived cells suspended in hydrogels (bioinks) allow to print tissues and organs for downstream medical applications. The bioprinted human tissues and organs are extremely valuable in regenerative medicine as bioprinting of autologous iPSC-derived organs eliminates the risk of immune rejection with organ transplants. Disease modeling and drug screening in bioprinted human tissues will give more precise information on disease mechanisms, drug efficacy, and drug toxicity than experimenting on animal models. Bioprinted iPSC-derived cancer tissues will aid in the study of early cancer development and precision oncology to discover patient-specific drugs. In this review, we present a brief summary of the combined use of two powerful technologies, iPSC technology, and 3D bioprinting in health-care applications.

The application of 3D bioprinting in urological diseases

In recent years, due to the increase in diseases that require organ/tissue transplantation and the limited donor, on the other hand, patients have lost hope of recovery and organ transplantation. Regenerative medicine is one of the new sciences that promises a bright future for these patients by providing solutions to repair, improve function, and replace tissue. One of the technologies used in regenerative medicine is three-dimensional (3D) bioprinters. Bioprinting is a new strategy that is the basis for starting a global revolution in the field of medical sciences and has attracted much attention. 3D bioprinters use a combination of advanced biology and cell science, computer science, and materials science to create complex bio-hybrid structures for various applications. The capacity to use this technology can be demonstrated in regenerative medicine to make various connective tissues, such as skin, cartilage, and bone. One of the essential parts of a 3D bioprinter is the bio-ink. Bio-ink is a combination of biologically active molecules, cells, and biomaterials that make the printed product. In this review, we examine the main bioprinting strategies, such as inkjet printing, laser, and extrusion-based bioprinting, as well as some of their applications.

3D bioprinting is an emerging technology that uses computer printing technology and unique bio-ink components to create artificial organs and biomedical objects. It is an interdisciplinary development technology integrating biology, chemistry, materials science, life science and other disciplines, and the technology behind biological 3D printing has improved in its development over the past few decades. Precisely printed biomaterials could benefit both tissue engineering and regenerative medicine. 3D bioprinting technology makes it possible to print tissues and organs, providing favorable conditions for organ transplantation and medical experiments. This paper mainly reviews the development of bioprinting technology and related concepts. According to the morphological change and chemical composition, the commonly used bioprinting materials (bio-inks) and their characteristics are described. The main methods of bioprinting are summarized, including traditional inkjet 3D bioprinting, extrusion 3D bioprinting, laser-assisted 3D bioprinting, photocuring 3D bioprinting and emerging 4D bioprinting and in situ bioprinting technologies. Finally, the paper introduces the development trend of bioprinting in the transplantation of skin, blood vessels and complex organs, as well as the precision research of tumors. In addition, current research challenges and prospects for future bioprinted 3D printing materials are discussed.

Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. In the last several years, organ bioengineering has been extensively explored to provide transplantable tissues or whole organs with the final goal of creating a three-dimensional growth microenvironment mimicking the native structure. It has been frequently reported that an extracellular matrix-based scaffold offers a structural support and important biological molecules that could help cellular proliferation during the recellularization process. The aim of the present review is to underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: (1) biological and synthetic scaffolds; (2) animal and human tissue decellularization; (3) scaffold recellularization; (4) 3D bioprinting; and (5) organoid technology. Future possible clinical applications in regenerative medicine for liver tissue engineering and for drug testing were underlined and dissected.