Bioactive Materials That Promote the Homing of Endogenous Mesenchymal Stem Cells to Improve Wound Healing.

Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

Liver organoids: updates on generation strategies and biomedical applications.

The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases.

Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction.

Damage to the central nervous system (CNS) often leads to irreversible neurological deficits, and there are currently few effective treatments available. However, recent advancements in regenerative medicine have identified CNS organoids as promising therapeutic options for addressing CNS injuries. These organoids, composed of various neurons and supporting cells, have shown potential for direct repair at injury sites. CNS organoids resemble the structure and function of actual brain tissue, which allows them to adapt and function well within the physiological environment when transplanted into injury sites. Research findings suggest that CNS organoids can replace damaged neurons, form new neural connections, and promote neural recovery. This review highlights the emerging benefits, evaluates preclinical transplantation outcomes, and explores future strategies for optimizing neuroregeneration using CNS organoids. With continued research and technological advancements, these organoids could provide new hope for patients suffering from neurological deficits.

Regenerative cell therapy with 3D bioprinting.

In situ additive biomanufacturing of structures may boost regenerative medicine.

Comparative Analysis of Exosomes and Extracellular Microvesicles in Healing Pathways: Insights for Advancing Regenerative Therapies.

Exosomes and microvesicles bear great potential to broaden therapeutic options in the clinical context. They differ in genesis, size, cargo, and composition despite their similarities. They were identified as participating in various processes such as angiogenesis, cell migration, and intracellular communication. Additionally, they are characterized by their natural biocompatibility. Therefore, researchers concluded that they could serve as a novel curative method capable of achieving unprecedented results. Indeed, in experiments, they proved remarkably efficient in enhancing wound regeneration and mitigating inflammation. Despite immense advancements in research on exosomes and microvesicles, the time for their large-scale application is yet to come. This article aims to gather and analyze current knowledge on those promising particles, their characteristics, and their potential clinical implementations.

Toward the latest advancements in cardiac regeneration using induced pluripotent stem cells (iPSCs) technology: approaches and challenges.

A novel approach to treating heart failures was developed with the introduction of iPSC technology. Knowledge in regenerative medicine, developmental biology, and the identification of illnesses at the cellular level has exploded since the discovery of iPSCs. One of the most frequent causes of mortality associated with cardiovascular disease is the loss of cardiomyocytes (CMs), followed by heart failure. A possible treatment for heart failure involves restoring cardiac function and replacing damaged tissue with healthy, regenerated CMs. Significant strides in stem cell biology during the last ten years have transformed the in vitro study of human illness and enhanced our knowledge of the molecular pathways underlying human disease, regenerative medicine, and drug development. We seek to examine iPSC advancements in disease modeling, drug discovery, iPSC-Based cell treatments, and purification methods in this article.

Amniotic membrane in wound healing: new perspectives.

There are several reasons for skin damage, including genetic factors, disorders, acute trauma, hard-to-heal wounds, or surgical interventions. Whatever the cause, wounds have a substantial impact on people who experience them, their caregivers and the healthcare system. Advanced wound care products have been researched and developed, providing an opportunity for faster and more complete healing. Tissue engineering (TE) is a promising strategy that can overcome limitations when choosing a graft for a wound. Amniotic membrane is a highly abundant, readily available, and inexpensive biological tissue that does not raise ethical concerns, with many applications in different fields of TE and regenerative medicine. It has attractive physical characteristics, such as elasticity, rigidity and mechanical strength, among others. The effects can also be potentiated by association with other substances, such as hyaluronic acid and growth factors. This paper describes new perspectives involving the use of amniotic membranes.

Advances in Nanomedicine and Biomaterials for Endometrial Regeneration: A Comprehensive Review.

The endometrium is an extremely important component of the uterus and is crucial for individual health and human reproduction. However, traditional methods still struggle to ideally repair the structure and function of damaged endometrium and restore fertility. Therefore, seeking and developing innovative technologies and materials has the potential to repair and regenerate damaged or diseased endometrium. The emergence and functionalization of various nanomedicine and biomaterials, as well as the proposal and development of regenerative medicine and tissue engineering techniques, have brought great hope for solving these problems. In this review, we will summarize various nanomedicine, biomaterials, and innovative technologies that contribute to endometrial regeneration, including nanoscale exosomes, nanomaterials, stem cell-based materials, naturally sourced biomaterials, chemically synthesized biomaterials, approaches and methods for functionalizing biomaterials, as well as the application of revolutionary new technologies such as organoids, organ-on-chips, artificial intelligence, etc. The diverse design and modification of new biomaterials endow them with new functionalities, such as microstructure or nanostructure, mechanical properties, biological functions, and cellular microenvironment regulation. It will provide new options for the regeneration of endometrium, bring new hope for the reconstruction and recovery of patients' reproductive abilities.

Clinical and preclinical approach in AGA treatment: a review of current and new therapies in the regenerative field.

Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application. Therefore, a new therapeutic approach is needed to promote regenerative enhancement alternatives. These treatment options, focused on the cellular niche restoration, could be the solution to the impact of dihydrotestosterone in the hair follicle microenvironment. In this context emerging regenerative therapies such as Platelet-rich plasma or Platelet-rich fibrine as well as hair follicle stem cells and mesenchymal stem cell based therapies and their derivatives (conditioned medium CM or exoxomes) are highlighting in the evolving landscape of hair restoration. Nanotechnology is also leading the way in AGA treatment through the design of bioinks and nanobiomaterials whose structures are being configuring in a huge range of cases by means of 3D bioprinting. Due to the increasing number and the rapid creation of new advanced therapies alternatives in the AGA field, an extended review of the current state of art is needed. In addition this review provides a general insight in current and emerging AGA therapies which is intented to be a guidance for researchers highlighting the cutting edge treatments which are recently gaining ground.

Optimizing Mesenchymal Stem Cells for Regenerative Medicine: Influence of Diabetes, Obesity, Autoimmune, and Inflammatory Conditions on Therapeutic Efficacy: A Review.

Mesenchymal stem cells (MSCs) are a promising tool that may be used in regenerative medicine. Thanks to their ability to differentiate and paracrine signaling, they can be used in the treatment of many diseases. Undifferentiated MSCs can support the regeneration of surrounding tissues through secreted substances and exosomes. This is possible thanks to the production of growth factors. These factors stimulate the growth of neighboring cells, have an anti-apoptotic effect, and support angiogenesis, and MSCs also have an immunomodulatory effect. The level of secreted factors may vary depending on many factors. Apart from the donor's health condition, it is also influenced by the source of MSCs, methods of harvesting, and even the banking of cells. This work is a review of research on how the patient's health condition affects the properties of obtained MSCs. The review discusses the impact of the patient's diabetes, obesity, autoimmune diseases, and inflammation, as well as the impact of the source of MSCs and methods of harvesting and banking cells on the phenotype, differentiation capacity, anti-inflammatory, angiogenic effects, and proliferation potential of MSCs. Knowledge about specific clinical factors allows for better use of the potential of stem cells and more appropriate targeting of procedures for collecting, multiplying, and banking these cells, as well as for their subsequent use. This article aims to review the characteristics, harvesting, banking, and paracrine signaling of MSCs and their role in diabetes, obesity, autoimmune and inflammatory diseases, and potential role in regenerative medicine.

A value hierarchy for inclusive design of heart valve implants in regenerative medicine.

Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase.Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants.Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need.Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need.

Scientists in the field of regenerative medicine are developing a new type of heart valve implant. After implantation, the synthetic implant slowly breaks down and is replaced by a new living heart valve. These so-called regenerative implants promise a complete cure. However, they also raise ethical questions. For example, questions related to justice and inclusion. In this paper, we explore how regenerative implants can be designed to be inclusive, meaning suitable, respectful and available for everyone. We argue that the design of regenerative implants should be adapted to relevant differences between users. The implants should be affordable in the short and long term. The implants should be suitable for use worldwide. The implants should be designed by teams of diverse age, gender and ethnicity. Users should be engaged in the design. And the communication about the implants to researchers and users should be inclusive. Overall, this paper provides ethical guidance to researchers and clinicians developing regenerative implants.

Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities.

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.

Recent advances in artificial intelligent strategies for tissue engineering and regenerative medicine.

BACKGROUND: Tissue engineering and regenerative medicine (TERM) aim to repair or replace damaged or lost tissues or organs due to accidents, diseases, or aging, by applying different sciences. For this purpose, an essential part of TERM is the designing, manufacturing, and evaluating of scaffolds, cells, tissues, and organs. Artificial intelligence (AI) or the intelligence of machines or software can be effective in all areas where computers play a role. METHODS: The "artificial intelligence," "machine learning," "tissue engineering," "clinical evaluation," and "scaffold" keywords used for searching in various databases and articles published from 2000 to 2024 were evaluated. RESULTS: The combination of tissue engineering and AI has created a new generation of technological advancement in the biomedical industry. Experience in TERM has been refined using advanced design and manufacturing techniques. Advances in AI, particularly deep learning, offer an opportunity to improve scientific understanding and clinical outcomes in TERM. CONCLUSION: The findings of this research show the high potential of AI, machine learning, and robots in the selection, design, and fabrication of scaffolds, cells, tissues, or organs, and their analysis, characterization, and evaluation after their implantation. AI can be a tool to accelerate the introduction of tissue engineering products to the bedside. HIGHLIGHTS: The capabilities of artificial intelligence (AI) can be used in different ways in all the different stages of TERM and not only solve the existing limitations, but also accelerate the processes, increase efficiency and precision, reduce costs, and complications after transplantation. ML predicts which technologies have the most efficient and easiest path to enter the market and clinic. The use of AI along with these imaging techniques can lead to the improvement of diagnostic information, the reduction of operator errors when reading images, and the improvement of image analysis (such as classification, localization, regression, and segmentation).

Cholangiocyte Organoids in Liver Transplantation; a Comprehensive Review.

Liver transplantation is the only curative option for many liver diseases that end up in liver failure, and cholangiopathy remains a challenging complication post-liver transplant, associated with significant morbidity and potential graft loss. The low availability of organs and high demand for transplantation motivate scientists to find novel interventions. Organoids, as three-dimensional cell cultures derived from adult cells or induced pluripotent cells, may help to address this problem. Different types of organoids have been described, from which cholangiocyte organoids offer a high level of versatility and plasticity for a deeper study of liver disease mechanisms. Cholangiocytes can be obtained from different segments of the biliary tree and have shown a remarkable capacity to adapt to new environments, presenting an effective system for studying cholangiopathies. Studies using cholangiocyte organoids show promising results for disease modeling, where organoids offer fundamental features to recapitulate the complexities of tissues in vitro and uncover fundamental pathological pathways to potentially reveal therapeutic strategies for personalized medicine. Organoids could hold the potential for regeneration of injured livers, representing tools of clinical impact in regenerative medicine when tissue damage is already present.

Multifunctional Biocomposites: Synthesis, Characterization, and Prospects for Regenerative Medicine and Controlled Drug Delivery.

This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.

Extracellular vesicles meet mitochondria: Potential roles in regenerative medicine.

Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic organelles responsible for energy production and cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including mitochondrial DNA (mtDNA), proteins, and intact mitochondria. Intriguingly, mitochondria are crucial mediators of EVs release, suggesting an interplay between EVs and mitochondria and their potential implications in physiology and pathology. However, in this expanding field, much remains unknown regarding the function and mechanism of crosstalk between EVs and mitochondria and the transport of mitochondrial EVs. Herein, we shed light on the physiological and pathological functions of EVs and mitochondria, potential mechanisms underlying their interactions, delivery of mitochondria-rich EVs, and their clinical applications in regenerative medicine.

Overcoming big bottlenecks in vascular regeneration.

Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.

Clinical Applications of Exosomes: A Critical Review.

Exosomes, small membrane-bound vesicles secreted by cells, have gained significant attention for their therapeutic potential. Measuring 30-100 nm in diameter and derived from various cell types, exosomes play a crucial role in intercellular communication by transferring proteins, lipids, and RNA between cells. This review analyzes existing literature on the clinical applications of exosomes. We conducted a comprehensive search of peer-reviewed articles and clinical trial data to evaluate the benefits, limitations, and challenges of exosome-based therapies. Key areas of focus included regenerative medicine, cancer therapy, gene therapy, and diagnostic biomarkers. This review highlights the vast clinical applications of exosomes. In regenerative medicine, exosomes facilitate tissue repair and regeneration. In cancer therapy, exosomes can deliver therapeutic agents directly to tumor cells. In gene therapy, exosomes serve as vectors for gene delivery. As diagnostic biomarkers, they are useful in diagnosing various diseases. Challenges such as the isolation, purification, and characterization of exosomes were identified. Current clinical trials demonstrate the potential of exosome-based therapies, though they also reveal significant hurdles. Regulatory issues, including the need for standardization and validation of exosome products, are critical for advancing these therapies. While significant progress has been made in understanding exosome biology, further research is essential to fully unlock their clinical potential. Addressing challenges in isolation, purification, and regulatory standardization is crucial for their successful application in clinical practice. This review provides a concise overview of the clinical applications of exosomes, emphasizing both their therapeutic promise and the obstacles that need to be overcome.