Tissue Engineering. Part B, Reviews最新文献

Cardiovascular diseases, considered the deadliest worldwide by the World Health Organization (WHO), lack effective therapies for regenerating cardiomyocytes. With their self-renewal and pluripotency capabilities, stem cell therapies are increasingly used in precision medicine. Induced pluripotent stem cells (iPSCs) are a promising alternative to embryonic stem cells. Good Manufacturing Practice (GMP) principles are not yet adapted for large-scale production of iPSCs. Additionally, the quality risk for iPSC products may not always be possible to eliminate, potentially jeopardizing the health of patients. This review aims to identify critical quality attributes (CQAs) for iPSC-derived cardiomyocytes (iPSC-CMs) for the development of cardiovascular therapy to ensure compliance with regulations and safety for patients. To attain these goals, the literature review was conducted with articles related to iPSCs and iPSC-CM therapies, legislation, and regulatory guidelines of the European Medicines Agency (EMA), Food and Drug Administration (FDA), and Pharmaceuticals and Medical Devices Agency (PMDA). In conclusion, additional regulations and guidelines are needed to monitor differentiation, maturation, and tumorigenicity. GMP-compliant cell banks and fast-track approval systems may increase accessibility for patients.

In recent decades, cultured meat has received considerable interest as a sustainable alternative to traditional meat products, showing promise for addressing the inherent problems associated with conventional meat production. However, current limitations on the scalability of production and extremely high production costs have prevented their widespread adoption. Therefore, it is important to develop novel engineering strategies to overcome the current limitations in large-scale cultured meat production. Such engineering considerations have the potential for advancements in cultured meat production by providing innovative and effective solutions to the prevailing challenges. In this review, we discuss how engineering strategies have been utilized to advance cultured meat technology by categorizing the production processes of cultured meat into three distinct steps: (1) cell preparation; (2) cultured meat fabrication; and (3) cultured meat maturation. For each step, we provide a comprehensive discussion of the recent progress and its implications. In particular, we focused on the engineering considerations involved in each step of cultured meat production, with specific emphasis on large-scale production.

When skeletal and cardiac tissues are damaged, surgical approaches are not always successful and tissue regeneration approaches are investigated. Reports in the literature indicate that silica nanoparticles and bioactive glasses (BGs), including silicate bioactive glasses (e.g., 45S5 BG), phosphate glass fibers, boron-doped mesoporous BGs, borosilicate glasses, and aluminoborates, are promising for repairing skeletal muscle tissue. Silica nanoparticles and BGs have been combined with polymers to obtain aligned nanofibers and to maintain controlled delivery of nanoparticles for skeletal muscle repair. The literature indicates that cardiac muscle regeneration can be also triggered by the ionic products of BGs. This was observed to be due to the release of vascular endothelial growth factor and other growth factors from cardiomyocytes, which regulate endothelial cells to form capillary structures (angiogenesis). Specific studies, including both in vitro and in vivo approaches, are reviewed in this article. The analysis of the literature indicates that although the research field is still very limited, BGs are showing great promise for muscle tissue engineering and further research in the field should be carried out to expand our basic knowledge on the application of BGs in muscle (skeletal and cardiac) tissue regeneration. Impact statement This review highlights the potential of silica particles and bioactive glasses (BGs) for skeletal and cardiac tissue regeneration. These biomaterials create scaffolds triggering muscle cell differentiation. Ionic products from BGs stimulate growth factors, supporting angiogenesis in cardiac tissue repair. Further research is required to expand our know-how on silica particles and BGs in muscle tissue engineering.

The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined.

Exosomes are nanosized extracellular vesicles (EVs) that participate in intercellular communication through surface proteins and the delivery of internal cargo. The exosomes have gained attention for their potential as disease biomarkers and therapeutic agents. The therapeutic ability of exosomes has been verified by copious previous studies. Effective methods for extensive clinical applications are being researched for exosome-based regenerative therapies, including the application of 3D cultures to enhance exosome production and secretion, which can resolve limited exosome secretion from the parent cells. Cell culture has emerged as a crucial approach for biomedical research because of its many benefits. Both well-established continuous cell lines and primary cell cultures continue to be invaluable for basic research and clinical application. Previous studies have shown that three-dimensional cultured exosomes (3D-Exo) improve therapeutic properties and yields compared with traditional culture systems. Since the majority of studies have focused on exosomes derived from mesenchymal stem cells (MSC-Exo), this review will also concentrate on MSC-Exo. In this review, we will summarize the advantages of 3D-Exo and introduce the 3D culture system and methods of exosome isolation, providing scientific strategies for the diagnosis, treatment, and prognosis of a wide variety of diseases.

Anisotropically aligned collagen scaffolds mimic the microarchitectural properties of native tissue, possess superior mechanical properties, and provide the essential physicochemical cues to guide cell response. Biofabrication methodologies to align collagen fibers include mechanical, electrical, magnetic, and microfluidic approaches. Magnetic alignment of collagen was first published in 1983 but widespread use of this technique was hindered mainly due to the low diamagnetism of collagen molecules and the need for very strong tesla-order magnetic fields. Over the last decade, there is a renewed interest in the use of magnetic approaches that employ magnetic particles and low-level magnetic fields to align collagen fibers. In this review, the working principle, advantages, and limitations of different collagen alignment techniques with special emphasis on the magnetic alignment approach are detailed. Key findings from studies that employ high-strength magnetic fields and the magnetic particle-based approach to align collagen fibers are highlighted. In addition, the most common qualitative and quantitative image analyses methods to assess collagen alignment are discussed. Finally, current challenges and future directions are presented for further development and clinical translation of magnetically aligned collagen scaffolds.

Impact Statement The current article examines urethral reconstruction on three fronts: presently available grafts, clinical trials, and preclinical studies. In this context, studies have focused on various types of biomaterial grafts, including natural, synthetic, and decellularized, combined with or without cells or growth factors, aiming to improve outcomes at both clinical and pre-clinical stages. Subsequently, four stages in the commercialization regulatory pathway in urethra engineering were examined, focusing on the commercialization challenges, particularly those associated with urethral products. Finally, the forthcoming challenges in urethra engineering and potential solutions for its enhancement have been explored. [Figure: see text].

Cartilage tissue, encompassing hyaline cartilage, fibrocartilage, and elastic cartilage, plays a pivotal role in the human body because of its unique composition, structure, and biomechanical properties. However, the inherent avascularity and limited regenerative capacity of cartilage present significant challenges to its healing following injury. This review provides a comprehensive analysis of the current state of cartilage tissue engineering, focusing on the critical components of cell sources, scaffolds, and growth factors tailored to the regeneration of each cartilage type. We explore the similarities and differences in the composition, structure, and biomechanical properties of the three cartilage types and their implications for tissue engineering. A significant emphasis is placed on innovative strategies for cartilage regeneration, including the potential for in situ transformation of cartilage types through microenvironmental manipulation, which may offer novel avenues for repair and rehabilitation. The review underscores the necessity of a nuanced approach to cartilage tissue engineering, recognizing the distinct requirements of each cartilage type while exploring the potential of transforming one cartilage type into another as a flexible and adaptive repair strategy. Through this detailed examination, we aim to broaden the understanding of cartilage tissue engineering and inspire further research and development in this promising field.

Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.

The dura mater, the furthest and strongest layer of the meninges, is crucial for protecting the brain and spinal cord. Its biomechanical behavior is vital, as any alterations can compromise biological functions. In recent decades, interest in the dura mater has increased due to the need for hermetic closure of dural defects prompting the development of several substitutes. Collagen-based dural substitutes are common commercial options, but they lack the complex biological and structural elements of the native dura mater, impacting regeneration and potentially causing complications like wound/postoperative infection and cerebrospinal fluid (CSF) leakage. To face this issue, recent tissue engineering approaches focus on creating biomimetic dura mater substitutes. The objective of this review is to discuss whether mimicking the mechanical properties of native tissue or ensuring high biocompatibility and bioactivity is more critical in developing effective dural substitutes, or if both aspects should be systematically linked. After a brief description of the properties and architecture of the native cranial dura, we describe the advantages and limitations of biomimetic dura mater substitutes to better understand their relevance. In particular, we consider biomechanical properties' impact on dura repair's effectiveness. Finally, the obstacles and perspectives for developing the ideal dural substitute are explored.