Tissue Engineering Of Organs Research Articles

Statement of Retraction: The first Stem Cell-Based Tissue-Engineered Organ Replacement: Implications for Regenerative Medicine and Society.

Statement of Retraction: The first Stem Cell-Based Tissue-Engineered Organ Replacement: Implications for Regenerative Medicine and Society.

Hydrogel-Based Vascularized Organ Tissue Engineering: A Systematized Review on Abdominal Organs.

Biomedical engineering, especially tissue engineering, is trying to provide an alternative solution to generate functional organs/tissues for use in various applications. These include beyond the final goal of transplantation, disease modeling and drug discovery as well. The aim of this study is to comprehensively review the existing literature on hydrogel-based vascularized organ (i.e., liver, pancreas, kidneys, intestine, stomach and spleen) tissue engineering of the abdominal organs. A comprehensive literature search was conducted on the Scopus database (latest search 1 September 2024). The research studies including hydrogel-based vascularized organ tissue engineering in the organs examined here were eligible for the review. Herein, 18 studies were included. Specifically, 10 studies included the liver or hepatic tissue, 5 studies included the pancreas or pancreatic islet tissue, 3 studies included the kidney or renal tissue, 1 study included the intestine or intestinal or bowel tissue, 1 study included the stomach or gastric tissue, and 0 studies included spleen tissue. Hydrogels are biocompatible materials with ideal characteristics for use as scaffolds. Even though organ tissue engineering is a rapidly growing field, there are still many obstacles to overcome to create a fully functional and long-lasting organ.

Current trends and research topics regarding organoids: A bibliometric analysis of global research from 2000 to 2023

The use of animal models for biological experiments is no longer sufficient for research related to human life and disease. The development of organ tissues has replaced animal models by mimicking the structure, function, development and homeostasis of natural organs. This provides more opportunities to study human diseases such as cancer, infectious diseases and genetic disorders. In this study, bibliometric methods were used to analyze organoid-related articles published over the last 20+ years to identify emerging trends and frontiers in organoid research. A total of 13,143 articles from 4125 institutions in 86 countries or regions were included in the analysis. The number of papers increased steadily over the 20-year period. The United States was the leading country in terms of number of papers and citations. Harvard Medical School had the highest number of papers published. Keyword analysis revealed research trends and focus areas such as organ tissues, stem cells, 3D culture and tissue engineering. In conclusion, this study used bibliometric and visualization methods to explore the field of organoid research and found that organ tissues are receiving increasing attention in areas such as cancer, drug discovery, personalized medicine, genetic disease modelling and gene repair, making them a current research hotspot and a future research trend.

Decellularized porcine vena cava grafts are fully repopulated after orthotopic implantation

Tissue-engineered organs, based on native extracellular matrix (ECM) scaffolds, could be a game changer in regenerative medicine applications. Decellularization technology provides such scaffolds with organ-typic ECM composition and architecture. Despite limitations such as the requirement of huge cell numbers and finding the optimal route of entry, recellularized scaffolds provide alternative grafts for transplantation. In this study we assessed whether decellularized scaffolds, when implanted, are repopulated from the adjacent tissue. Since the vasculature plays an important role in tissue functionality, our main focus was to evaluate in situ repopulation of decellularized veins in a pig model. For this, porcine inferior vena cava grafts were decellularized and orthotopically implanted in recipient pigs (n = 12). To evaluate possible immune responses to the scaffolds and to assess potential thrombus formation, cellular allogeneic vena cava grafts were transplanted in control pigs (n = 8). Within 28 days after implantation, the decellularized veins were fully recellularized with endothelial cells and smooth muscle cells. Quantitative histological analysis showed a comparable amount of smooth muscle actin in the repopulated decellularized grafts similar to the native IVC. Lymphocyte infiltrates representing signs of graft rejection were not detected in the pigs, as opposed to the control group that received the allogeneic grafts. The decellularized grafts provoked a higher incidence of thrombosis in comparison with allogeneic grafts (33.3 vs. 12.5%). With this study, we show efficient in situ repopulation of decellularized vein grafts. These findings are insightful and promising to further explore the use of decellularized tissue without the need for full pre-transplant recellularization.Graphical abstract

Application of Artificial Intelligence in Tissue Engineering.

Tissue engineering, a crucial approach in medical research and clinical applications, aims to regenerate damaged organs. By combining stem cells, biochemical factors, and biomaterials, it encounters challenges in designing complex 3D structures. Artificial intelligence (AI) enhances tissue engineering through computational modeling, biomaterial design, cell culture optimization, and personalized medicine. This review explores AI applications in organ tissue engineering (bone, heart, nerve, skin, cartilage), employing various machine learning (ML) algorithms for data analysis, prediction, and optimization. Each section discusses common ML algorithms and specific applications, emphasizing the potential and challenges in advancing regenerative therapies.

Development of Biocompatible 3D-Printed Artificial Blood Vessels through Multidimensional Approaches.

Within the human body, the intricate network of blood vessels plays a pivotal role in transporting nutrients and oxygen and maintaining homeostasis. Bioprinting is an innovative technology with the potential to revolutionize this field by constructing complex multicellular structures. This technique offers the advantage of depositing individual cells, growth factors, and biochemical signals, thereby facilitating the growth of functional blood vessels. Despite the challenges in fabricating vascularized constructs, bioprinting has emerged as an advance in organ engineering. The continuous evolution of bioprinting technology and biomaterial knowledge provides an avenue to overcome the hurdles associated with vascularized tissue fabrication. This article provides an overview of the biofabrication process used to create vascular and vascularized constructs. It delves into the various techniques used in vascular engineering, including extrusion-, droplet-, and laser-based bioprinting methods. Integrating these techniques offers the prospect of crafting artificial blood vessels with remarkable precision and functionality. Therefore, the potential impact of bioprinting in vascular engineering is significant. With technological advances, it holds promise in revolutionizing organ transplantation, tissue engineering, and regenerative medicine. By mimicking the natural complexity of blood vessels, bioprinting brings us one step closer to engineering organs with functional vasculature, ushering in a new era of medical advancement.

Current Challenges and Future Promise for Use of Extracellular Matrix Scaffold to Achieve the Whole Organ Tissue Engineering Moonshot.

Whole organ tissue engineering encompasses a variety of approaches, including 3D printed tissues, cell-based self-assembly, and cellular incorporation into synthetic or xenogeneic extracellular matrix (ECM) scaffolds. This review article addresses the importance of whole organ tissue engineering for various solid organ applications, focusing on the use of extracellular (ECM) matrix scaffolds in such engineering endeavors. In this work, we focus on the emerging barriers to translation of ECM scaffold-based tissue-engineered organs and highlight potential solutions to overcome the primary challenges in the field. The 3 main factors that are essential for developing ECM scaffold-based whole organs are (1) recapitulation of a functional vascular tree, (2) delivery and orientation of cells into parenchymal void spaces left vacant in the scaffold during the antigen elimination and associated cellular removal processes, and (3) driving differentiation of delivered cells toward the appropriate site-specific lineage. The insights discussed in this review will allow the potential of allogeneic or xenogeneic ECM scaffolds to be fully maximized for future whole organ tissue-engineering efforts.

A new approach of using organ-on-a-chip and fluid-structure interaction modeling to investigate biomechanical characteristics in tissue-engineered blood vessels.

The tissue-engineered blood vessel (TEBV) has been developed and used in cardiovascular disease modeling, preclinical drug screening, and for replacement of native diseased arteries. Increasing attention has been paid to biomechanical cues in TEBV and other tissue-engineered organs to better recapitulate the functional properties of the native organs. Currently, computational fluid dynamics models were employed to reveal the hydrodynamics in TEBV-on-a-chip. However, the biomechanical wall stress/strain conditions in the TEBV wall have never been investigated. In this paper, a straight cylindrical TEBV was placed into a polydimethylsiloxane-made microfluidic device to construct the TEBV-on-a-chip. The chip was then perfused with cell culture media flow driven by a peristaltic pump. A three-dimensional fluid-structure interaction (FSI) model was generated to simulate the biomechanical conditions in TEBV and mimic both the dynamic TEBV movement and pulsatile fluid flow. The material stiffness of the TEBV wall was determined by uniaxial tensile testing, while the viscosity of cell culture media was measured using a rheometer. Comparison analysis between the perfusion experiment and FSI model results showed that the average relative error in diameter expansion of TEBV from both approaches was 10.0% in one period. For fluid flow, the average flow velocity over a period was 2.52cm/s from the FSI model, 10.5% higher than the average velocity of the observed cell clusters (2.28mm/s) in the experiment. These results demonstrated the facility to apply the FSI modeling approach in TEBV to obtain more comprehensive biomechanical results for investigating mechanical mechanisms of cardiovascular disease development.

Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate ischemic injury.

Myocardial hypoxia is the low oxygen tension in the heart tissue implicated in many diseases, including ischemia, cardiac dysfunction, or after heart procurement for transplantation. Oxygen-generating microparticles have recently emerged as a potential strategy for supplying oxygen to sustain cell survival, growth, and tissue functionality in hypoxia. Here, we prepared oxygen-generating microparticles with poly D,L-lactic-co-glycolic acid, and calcium peroxide (CPO), which yielded a continuous morphology capable of sustained oxygen release for up to 24h. We demonstrated that CPO microparticles increased primary rat cardiomyocyte metabolic activity while not affecting cell viability during hypoxia. Moreover, hypoxia-inducible factor (HIF)-1α, which is upregulated during hypoxia, can be downregulated by delivering oxygen using CPO microparticles. Single-cell traction force microscopy data demonstrated that the reduced energy generated by hypoxic cells could be restored using CPO microparticles. We engineered cardiac tissues that showed higher contractility in the presence of CPO microparticles compared to hypoxic cells. Finally, we observed reduced myocardial injuries in ex vivo rabbit hearts treated with CPO microparticles. In contrast, an acute early myocardial injury was observed for the hearts treated with control saline solution in hypoxia. In conclusion, CPO microparticles improved cell and tissue contractility and gene expression while reducing hypoxia-induced myocardial injuries in the heart. STATEMENT OF SIGNIFICANCE: Oxygen-releasing microparticles can reduce myocardial ischemia, allograft rejection, or irregular heartbeats after heart transplantation. Here we present biodegradable oxygen-releasing microparticles that are capable of sustained oxygen release for more than 24 hrs. We then studied the impact of sustained oxygen release from microparticles on gene expresseion and cardiac cell and tissue function. Previous studies have not measured cardiac tissue or cell mechanics during hypoxia, which is important for understanding proper cardiac function and beating. Using traction force microscopy and an engineered tissue-on-a-chip, we demonstrated that our oxygen-releasing microparticles improve cell and tissue contractility during hypoxia while downregulating the HIF-1α expression level. Finally, using the microparticles, we showed reduced myocardial injuries in rabbit heart tissue, confirming the potential of the particles to be used for organ transplantation or tissue engineering.

Progressive use of nanocomposite hydrogels materials for regeneration of damaged cartilage and their tribological mechanical properties

Osteoarthritis (OA) is a non-inflammatory deteriorating debilitating state that bring about remarkable health and economic issues globally. Break down/deterioration of the articular cartilage (AC) is one of the pathologic characteristics of osteoarthritis (OA). Nanocomposite hydrogels (NCH) materials are evolving as a potential class of scaffolds for organ regeneration and tissue engineering. In recent years, innovative hydrogels specifically loaded with nanoparticles have been developed and synthesized with the goal of changing conventional cartilage treatments. The detailed development of a tailored nanocomposite hydrogels (NCH) material utilized for tissue engineering is presented in this review study. Also, the mechanical characteristics, particularly the tribological behavior, of these produced NCH have been highlighted. Large amounts of research and data on the hydrogel substance utilized in cartilage healing are summarized in the current review study. When determining future research gaps in the area of hydrogels for cartilage regeneration, such information will provide researchers an advantage to further develop NCH.

A High-Throughput and Uniform Amplification Method for Cell Spheroids.

Cell culture is an important life science technology. Compared with the traditional two-dimensional cell culture, three-dimensional cell culture can simulate the natural environment and structure specificity of cell growth in vivo. As such, it has become a research hotspot. The existing three-dimensional cell culture techniques include the hanging drop method, spinner flask method, etc., making it difficult to ensure uniform morphology of the obtained cell spheroids while performing high-throughput. Here, we report a method for amplifying cell spheroids with the advantages of quickly enlarging the culture scale and obtaining cell spheroids with uniform morphology and a survival rate of over 95%. Technically, it is easy to operate and convenient to change substances. These results indicate that this method has the potential to become a promising approach for cell–cell, cell–stroma, cell–organ mutual interaction research, tissue engineering, and anti-cancer drug screening.

A comprehensive review on applications of 3D printing in natural fibers polymer composites for biomedical applications

Over the past few decades, three-dimensional (3D) printing technologies have surpassed the conventional manufacturing techniques due to their wide applications and advantages. The applications of 3D printing in biomedical field is ever increasing due to improvement in accuracy and surface quality of products. The development of biomedical implants through patient specific data and rapid tooling techniques has revolutionized the research activities. Now-a-days, the metal printers have capability to directly create metal implants using biocompatible metallic alloys. This paper focuses on the potential applications of 3D printing in biomedical fields with specific emphasis on tissue engineering and bio-printing of organs using bio-inks. This paper also reviews various biocompatible and biodegradable materials used in recent in-vivo and in-vitro studies. It has been deduced from the study that use of natural fibers in polymers resulted in improved mechanical strength of products. Also, the implementation of additive manufacturing technologies for production of composites would lead to production of customized product.

Characterization of Decellularized Implants for Extracellular Matrix Integrity and Immune Response Elicitation.

Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs. omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and quantitative image analysis tools to comprehensively describe and compare the proteins following DC and postimplantation. Our data helped to identify any alteration postdecullarization as well implantation. We could also monitor route-specific modulation of the ECM and regulation of the immune responses (macrophage and T cells) following implantation. The current approach opens up the possibility to monitor the fate of biological scaffolds in terms of the ECM and immune response against the implants. In addition, the identification of different routes helped us to identify differential immune responses against the implants. This study opens up the potential to identify the changes associated with chemical DC both pre- and postimplantation, which could further help to promote research in this direction. Impact Statement The development of a biological scaffold helps in the preparation of a functional organ in the clinics. In the current study, we develop a strategy for chemical decellularization and explored two different routes to understand the differential responses elicited postimplantation. The use of sensitive protein and genomic tools to study the changes creates a favorable environment for similar efforts to develop and characterize biological scaffolds before further trials in the clinics. The current study, which was carried out without any immunosuppressive agents, could help to establish (a) appropriate chemical strategies for preparing biological scaffolds as well as (b) identify putative implantable routes to circumvent any adverse immune reactions, which will ultimately decide the outcome for acceptance or rejection of the scaffold/implant.

Poloxamer-Based Scaffolds for Tissue Engineering Applications: A Review.

Poloxamer is a triblock copolymer with amphiphilicity and reversible thermal responsiveness and has wide application prospects in biomedical applications owing to its multifunctional properties. Poloxamer hydrogels play a crucial role in the field of tissue engineering and have been regarded as injectable scaffolds for loading cells or growth factors (GFs) in the last few years. Hydrogel micelles can maintain the integrity and stability of cells and GFs and form an appropriate vascular network at the application site, thus creating an appropriate microenvironment for cell growth, nerve growth, or bone integration. The injectability and low toxicity of poloxamer hydrogels make them a noninvasive method. In addition, they can also be good candidates for bio-inks, the raw material for three-dimensional (3D) printing. However, the potential of poloxamer hydrogels has not been fully explored owing to the complex biological challenges. In this review, the latest progress and cutting-edge research of poloxamer-based scaffolds in different fields of application such as the bone, vascular, cartilage, skin, nervous system, and organs in tissue engineering and 3D printing are reviewed, and the important roles of poloxamers in tissue engineering scaffolds are discussed in depth.

Biomaterials to promote vascularization in tissue engineering organs and ischemic fibrotic diseases

AbstractThe formation of the complex and fully functional vascular networks in pivotal organs is a key challenge in tissue engineering research. Functional blood vessels not only maintain oxygen and nutrient delivery but also effectively get rid of waste. Recently, a deep understanding of the vascular tissue structure and tissue microenvironment helps to make several great progress in the construction of highly complex and biomimetic vascularized tissues and organs, using biomaterials such as hydrogels and biomaterial composites. In this review, we summarized the advantages and research progress of biomaterials used in constructing the vascularized tissue in tissue engineering regeneration, ischemic fibrosis, and so on. We also discussed the progression of vascularization in organs and organoids. First, we discuss the applications of biomaterial‐based vascularized tissue in bone, skin, and other tissue regeneration. Secondly, we discussed biomaterials and their components in promoting vascularization of ischemic fibrosis organs such as cerebral infarction, myocardial infarction, and renal fibrosis. In addition, we also introduced the strategies and applications that biomaterials function as a biomimetic extracellular matrix performed to construct vascularized tissues or organs in vitro. Finally, coming opportunities and challenges are also discussed and commented on.

PROTOTYPE OF 3D PRINTING ON RIBCAGE

Medical 3D printing is emerging as a clinically relevant imaging tool in Directing preoperative and intraoperative planning in many surgical specialties and will therefore likely lead to interdisciplinary collaboration between engineers, radiologists, and surgeons. 3D printer technology is one of the innovations brought by the industrial age. It has been in our lives for many years. This miracle manufacturing method has been frequently preferred for medical applications in recent years. The main aim of this project is to minimise the time and cost for the design and manufacturing of the prosthesis. Getting the DICOM file from the MRI or CT scan which gives the body part dimensions (or) views of the body part in different directions . AUTODESK MESHMIXER and 3D SLICER software’s are used to extract and design the 3D prosthetic body part in this project, flexible Biomaterial is gone to be used for the flexibility in the respiration process. There are a lot uses of 3D printing technology in surgery, pharmaceutical industry, disease modelling, development of customized implants and prostheses, organ printing, vet medicine and tissue engineering applications have been explained and this new method compared with traditional methods that used in the biomedical field. In addition, this study includes future opportunities that are expected to become widespread and developed in the future. Keywords: 3D Printing, DICOM File, AUTODESK MESHMIXER, 3D Slicer.

CRISPR/Cas9 editing of directly reprogrammed myogenic progenitors restores dystrophin expression in a mouse model of muscular dystrophy.

SummaryGenetic mutations in dystrophin manifest in Duchenne muscular dystrophy (DMD), the most commonly inherited muscle disease. Here, we report on reprogramming of fibroblasts from two DMD mouse models into induced myogenic progenitor cells (iMPCs) by MyoD overexpression in concert with small molecule treatment. DMD iMPCs proliferate extensively, while expressing myogenic stem cell markers including Pax7 and Myf5. Additionally, DMD iMPCs readily give rise to multinucleated myofibers that express mature skeletal muscle markers; however, they lack DYSTROPHIN expression. Utilizing an exon skipping-based approach with CRISPR/Cas9, we report on genetic correction of the dystrophin mutation in DMD iMPCs and restoration of protein expression in vitro. Furthermore, engraftment of corrected DMD iMPCs into the muscles of dystrophic mice restored DYSTROPHIN expression and contributed to the muscle stem cell reservoir. Collectively, our findings report on a novel in vitro cellular model for DMD and utilize it in conjunction with gene editing to restore DYSTROPHIN expression in vivo.

The reproductive potential of uterus transplantation: future prospects.

Background and aim:Absolute uterine factor infertility (AUFI) is a form of infertility whereby conception and/or maintenance of pregnancy is impossible as a result of uterine absence or its completed dysfunction. It affects 1/500 women of reproductive age while the incidence is about 8% of infertile couples. Uterus transplantation (UTx) has been gaining ground as a viable option to enable women with AUFI to have biological children and as an alternative to surrogacy, a highly controversial practice still banned in many countries.Methods:The authors have set out to strike a reasonable balance between UTx benefits and the still numerous risks, whether clinical or ethical, associated with such an innovative form of transplant, which is not life-saving, requires immunosuppression throughout pregnancy and the organ to be removed right after childbirth. For the purpose of this Focus-on, the authors have laid out an analysis of uterus transplantation (UTx) taking into account its potential in terms of enabling patients with AUFI to achieve motherhood and its ethical viability, by virtue of its unique traits as a life-giving/enhancing intervention.Results:While still far from achieving mainstream status, considerable strides have been made in UTx outcomes, with many live births already recorded. Procedures from living donor are reportedly more effective in terms of success rates. Organ tissue engineering has been explored and developed with promising results.Conclusions:UTx entails various risks and ethical quandaries which have to do with reproductive autonomy and rights. New human attempts and clinical trials of UTx should be performed to further optimize the procedure in relation to safety and effectiveness. Techniques such as tissue engineering could lead in the medium-long term to a wholly bioengineered uterus to be used for transplantation, relying on scaffolds from decellularized organs or tissues that can be recellularized by several types of autologous somatic/stem cells. Such advances hold promise in terms of solving UTx-related complications and organ supply difficulties. (www.actabiomedica.it)

AM to produce load-bearing prostheses: a viable technological perspective for now, in a near future, or never?

Additive Manufacturing technologies have opened new perspectives for the realization of tissue and organs substitutes. The main advantages come from the possibility of using the same technology to produce artificial or biological substitutes in a wide range of outer shapes and inner reticular architectures, which may pave the way to their use to produce personalized substitutes. Additive manufacturing technologies are based on layer-by-layer material fusion and deposition. As such, they have intrinsic limitations which may hinder the possibility to produce substitutes that meet the requirements for safe clinical use. As an example, discontinuities between layers may make the outer surface of a substitute significantly uneven, rough, and may even weaken the substitute mechanical properties in such an aggressive environment as the human body. Moreover, repeated thermal cycles (fusion and solidification) drastically limit the choice of materials which can be used. Finally, the outcome of the production technology is affected by many variables that it is not trivial to control to deliver the necessary quality and repeatability of the production process for medical applications. Indeed, the surface roughness of an implantable prosthesis or organ substitute is key to modulate cell adhesion and the susceptibility to chemical attack by body fluids. Structural strength is a mandatory requirement for load-bearing prostheses (e.g., orthopedic and dental prostheses). Materials for biomedical applications must not only be 3D printable, but also biocompatible and/or possibly have to promote cells growth and to prevent inflammatory reactions. The performance of artificial, bio artificial and tissue-engineered organs needs also to be certified and guaranteed, a rather difficult task to define for devices which may be unique, being tailored on the specific needs of the patient. In this paper, it will be discussed whether this technology is sufficiently mature to replace more traditional techniques or, alternatively, whether it should be limited to a restricted range of emergency applications until the existing relevant technological gaps are filled.

Molybdenum disulfide (MoS2)-based nanostructures for tissue engineering applications: prospects and challenges.

Molybdenum disulfide (MoS2) nanostructures have recently earned substantial thoughts from the scientific communities owing to their unique physicochemical, optical and electrical properties. Although MoS2 has been mostly highlighted for its industrial applications, its biological applicability has not been extensively explored. The introduction of nanotechnology in the field of tissue engineering has significantly contributed to human welfare by displaying advancement in tissue regeneration. Assimilation of MoS2 nanostructures into the polymer matrix has been considered a persuasive material of choice for futuristic tissue engineering applications. The current review provides a general discussion on the structural properties of different MoS2 nanostructures. Further, this article focuses on the interactions of MoS2 with biological systems in terms of its cellular toxicity, and biocompatibility along with its capability for cell proliferation, adhesion, and immunomodulation. The article continues to confer the utility of MoS2 nanostructure-based scaffolds for various tissue engineering applications. The article also highlights some emerging prospects and possibilities of the applicability of MoS2-based nanostructures in large organ tissue engineering. Finally, the article concludes with a brief annotation on the challenges and limitations that need to be overcome in order to make plentiful use of this wonderful material for tissue engineering applications.