Journal of Tissue Engineering最新文献

The liver coordinates over 500 biochemical processes crucial for maintaining homeostasis, detoxification, and metabolism. Its specialized cells, arranged in hexagonal lobules, enable it to function as a highly efficient metabolic engine. However, diseases such as cirrhosis, fatty liver disease, and hepatitis present significant global health challenges. Traditional drug development is expensive and often ineffective at predicting human responses, driving interest in advanced in vitro liver models utilizing 3D bioprinting and microfluidics. These models strive to mimic the liver's complex microenvironment, improving drug screening and disease research. Despite its resilience, the liver is vulnerable to chronic illnesses, injuries, and cancers, leading to millions of deaths annually. Organ shortages hinder liver transplantation, highlighting the need for alternative treatments. Tissue engineering, employing polymer-based scaffolds and 3D bioprinting, shows promise. This review examines these innovative strategies, including liver organoids and liver tissue-on-chip technologies, to address the challenges of liver diseases.

Graphene and its derivatives are widely used in tissue-engineering scaffolds, especially in the form of hydrogels. This is due to their biocompatibility, electrical conductivity, high surface area, and physicochemical versatility. They are also used in tissue engineering. Tissue engineering is suitable for 3D printing applications, and 3D printing makes it possible to construct 3D structures from 2D graphene, which is a revolutionary technology with promising applications in tissue and organ engineering. In this review, the recent literature in which graphene and its derivatives have been used as the major components of hydrogels is summarized. The application of graphene and its derivative-based hydrogels in tissue engineering is described in detail from different perspectives.

Exosomes are nano-sized extracellular vesicles (EVs) released by diverse types of cells, which affect the functions of targeted cells by transporting bioactive substances. As the main component of exosomes, non-coding RNA (ncRNA) is demonstrated to impact multiple pathways participating in bone healing. Herein, this review first introduces the biogenesis and secretion of exosomes, and elucidates the role of the main cargo in exosomes, ncRNAs, in mediating intercellular communication. Subsequently, the potential molecular mechanism of exosomes accelerating bone healing is elucidated from the following four aspects: macrophage polarization, vascularization, osteogenesis and osteoclastogenesis. Then, we systematically introduce construction strategies based on modified exosomes in bone regeneration field. Finally, the clinical trials of exosomes for bone healing and the challenges of exosome-based therapies in the biomedical field are briefly introduced, providing solid theoretical frameworks and optimization methods for the clinical application of exosomes in orthopedics.

Short sequences of amino acids called peptides have a wide range of biological functions and the potential to treat a number of diseases. Bioactive peptides can be derived from different sources, including marine organisms, and synthetic design, making them versatile candidates for production of therapeutic agents. Their therapeutic effects span across areas such as antimicrobial activity, cells proliferation and migration, synthesis of collagen, and more. This current review explores the fascinating realm of bioactive peptides as promising therapeutic agents for skin wound healing. This review focuses on the multifaceted biological effects of specific peptides, shedding light on their potential to revolutionize the field of dermatology and regenerative medicine. It delves into how these peptides stimulate collagen synthesis, inhibit inflammation, and accelerate tissue regeneration, ultimately contributing to the effective repair of skin wounds. The findings underscore the significant role several types of bioactive peptides can play in enhancing wound healing processes and offer promising insights for improving the quality of life for individuals with skin injuries and dermatological conditions. The versatility of peptides allows for the development of tailored treatments catering to specific wound types and patient needs. As continuing to delve deeper into the realm of bioactive peptides, there is immense potential for further exploration and innovation. Future endeavors may involve the optimization of peptide formulations, elucidation of underlying molecular and cellular mechanisms.

Stem cell-mediated bio-root regeneration is an alternative tooth replacement strategy; however, physiologically functional bio-root regeneration with distinctive dentin structure remains challenging. In this study, the distinct arrangements of collagen fibril bundles were identified that account for hierarchical structural differences between dentin, cementum, and alveolar bone. Thus, an "engineered pre-dentin" was fabricated, which was a dentin hierarchical structure mimicking collagen (MC) scaffold, with well-aligned hierarchical mineralized collagen fibril bundles. The results revealed that it has a stronger effect on promoting biological root regeneration in nude mice and miniature pigs with dental pulp stem cell (DPSC) and periodontal ligament stem cell (PDLSC) sheets compared to hydroxyapatite tricalcium phosphate (HA/TCP). The success rate in the MC group was also higher than that in the HA/TCP group (67% and 33%, respectively). In conclusion, the hierarchical dentin-mimicking scaffold can enhance the regeneration of bio-roots, which provides a promising strategy for tooth regeneration.

This study investigated the therapeutic potential of a manganese dioxide-polymer dot (MnO2-PD)-incorporated hydrogel, designated as M-PD hydrogel, for modulating reactive oxygen species (ROS) within the osteoarthritis (OA) environment. Our research highlights the ability of the hydrogel to scavenge ROS, thereby influencing the differentiation of osteoclasts and protecting chondrocytes, offering a novel approach to osteoarthritis (OA) management. Our results indicated that the M-PD hydrogel increased electrical resistance and fluorescence recovery in the presence of osteoclasts, correlating with decreased ROS levels and suppressed expression of osteoclast differentiation markers. Coculture experiments revealed the protective effects of the hydrogel on chondrocytes by reducing the expression of matrix-degrading enzymes. In vivo application in burr holes and/or OA-induced mice revealed a significant reduction in osteoclast formation and cartilage destruction, suggesting the dual therapeutic action of the hydrogel in altering the joint microenvironment. These findings highlight the potential of targeting ROS in osteoclasts as a comprehensive therapeutic approach, offering not only symptomatic relief but also targeting the underlying mechanisms of disease progression in OA.

Three-dimensional (3D) bioprinting has emerged as a promising strategy for fabricating complex tissue analogs with intricate architectures, such as vascular networks. Achieving this necessitates bioink formulations that possess highly printable properties and provide a cell-friendly microenvironment mimicking the native extracellular matrix. Rapid advancements in printing techniques continue to expand the capabilities of researchers, enabling them to overcome existing biological barriers. This review offers a comprehensive examination of ultraviolet-based 3D bioprinting, renowned for its exceptional precision compared to other techniques, and explores its applications in inducing angiogenesis across diverse tissue models related to hypoxia. The high-precision and rapid photocuring capabilities of 3D bioprinting are essential for accurately replicating the intricate complexity of vascular networks and extending the diffusion limits for nutrients and gases. Addressing the lack of vascular structure is crucial in hypoxia-related diseases, as it can significantly improve oxygen delivery and overall tissue health. Consequently, high-resolution 3D bioprinting facilitates the creation of vascular structures within three-dimensional engineered tissues, offering a potential solution for addressing hypoxia-related diseases. Emphasis is placed on fundamental components essential for successful 3D bioprinting, including cell types, bioink compositions, and growth factors highlighted in recent studies. The insights provided in this review underscore the promising prospects of leveraging 3D printing technologies for addressing hypoxia-related diseases through the stimulation of angiogenesis, complementing the therapeutic efficacy of cell therapy.

Impaired wound healing poses a significant burden on the healthcare system and patients. Stem cell therapy has demonstrated promising potential in the treatment of wounds. However, its clinical application is hindered by the low efficiency of cell homing. In this study, we successfully integrated P-selectin glycoprotein ligand-1 (PSGL-1) into the genome of human adipose-derived mesenchymal stem cells (ADSCs) using a Cas9-AAV6-based genome editing tool platform. Our findings revealed that PSGL-1 knock-in enhanced the binding of ADSCs to platelets and their adhesion to the injured site. Moreover, the intravenous infusion of PSGL-1 -engineered ADSCs (KI-ADSCs) significantly improved the homing efficiency and residence rate at the site of skin lesions in mice. Mechanistically, PSGL-1 knock-in promotes the release of some therapeutic cytokines by activating the canonical WNT/β-catenin signaling pathway and accelerates the healing of wounds by promoting angiogenesis, re-epithelialization, and granulation tissue formation at the wound site. This study provides a novel strategy to simultaneously address the problem of poor migration and adhesion of mesenchymal stem cells (MSCs).

Our prior research has effectively developed tissue-engineered vascularized oral mucosa equivalents (VOME); however, challenges such as low repeatability and stability, as well as the inability to accurately replicate the complexity of real blood vessels, were encountered. Therefore, this study aimed to screen the VOME and native oral mucosa vascular homeostasis phenotypes by tandem mass tag-tagged proteomics associated with laser capture microdissection and human angiogenesis antibody array technology. Then, lentiviruses were constructed and stably transfected with vascular endothelial-like cells (VELCs) to detect angiogenic capacity. HE, EdU Apollo tracer staining, immunofluorescence staining, scanning electron microscopy, biomechanical testing, and a small animal ultrasound imaging system were used to analyze the characteristics of vascularization homeostasis and monitor functional regeneration of the vascularized homeostatic phenotypic oral mucosal equivalents (VHPOME). The results showed that PGAM1, COL5A1, ANG, and RNH1 are potential specific angiogenesis phenotypes. High expression of PGAM1, COL5A1, and ANG and/or low expression of RNH1 can promote the angiogenesis of VOME. ANG/shRNH1 has the most significant tube-like structure-formation ability. The expression of PGAM1, COL5A1, and ANG in the VHPOME group was higher than that of the control group, and the expression of RNH1 was lower than that of the control group. COL5A1/ANG can significantly improve the mechanical properties. The blood flow signal was most significant in the ANG/shRNH1 group. PGAM1, COL5A1, ANG, shRNH1, PGAM1/ANG, COL5A1/ANG, PGAM1/shRNH1, PGAM1/shRNH1, COL5A1/shRNH1, and ANG/shRNH1 may be the targets for establishing vascularization homeostasis and functional regeneration of oral mucosal equivalent genes (groups), and ANG/shRNH1 has the most significant effect.

Articular cartilage defect therapy is still dissatisfactory in clinic. Direct cell implantation faces challenges, such as tumorigenicity, immunogenicity, and uncontrollability. Extracellular vesicles (EVs) based cell-free therapy becomes a promising alternative approach for cartilage regeneration. Even though, EVs from different cells exhibit heterogeneous characteristics and effects. The aim of the study was to discover the functions of EVs from the cells during chondrogenesis timeline on cartilage regeneration. Here, bone marrow mesenchymal stem cells (BMSCs)-EVs, juvenile chondrocytes-EVs, and adult chondrocytes-EVs were used to represent the EVs at different differentiation stages, and fibroblast-EVs as surrounding signals were also joined to compare. Fibroblasts-EVs showed the worst effect on chondrogenesis. While juvenile chondrocyte-EVs and adult chondrocyte-EVs showed comparable effect on chondrogenic differentiation as BMSCs-EVs, BMSCs-EVs showed the best effect on cell proliferation and migration. Moreover, the amount of EVs secreted from BMSCs were much more than that from chondrocytes. An injectable decellularized extracellular matrix (dECM) hydrogel from small intestinal submucosa (SIS) was fabricated as the EVs delivery platform with natural matrix microenvironment. In a rat model, BMSCs-EVs loaded SIS hydrogel was injected into the articular cartilage defects and significantly enhanced cartilage regeneration in vivo. Furthermore, protein proteomics revealed BMSCs-EVs specifically upregulated multiple metabolic and biosynthetic processes, which might be the potential mechanism. Thus, injectable SIS hydrogel loaded with BMSCs-EVs might be a promising therapeutic way for articular cartilage defect.