Journal of Tissue Engineering最新文献

{"title":"Discovery of bioactive peptides as therapeutic agents for skin wound repair.","authors":"Nur Izzah Md Fadilah, Nurul Aqilah Shahabudin, Raniya Adiba Mohd Razif, Arka Sanyal, Anushikha Ghosh, Khairul Idzwan Baharin, Haslina Ahmad, Manira Maarof, Antonella Motta, Mh Busra Fauzi","doi":"10.1177/20417314241280359","DOIUrl":"https://doi.org/10.1177/20417314241280359","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241280359"},"PeriodicalIF":6.7,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered pre-dentin with well-aligned hierarchical mineralized collagen fibril bundles promote bio-root regeneration.","authors":"Lei Hu, Dongmei Cheng, Xin Yuan, Zhenhua Gao, Qiao Yi, Bin Zhao, Fulan Wei, Junji Xu, Zhipeng Fan, Yi Liu, Xiumei Wang, Fuzhai Cui, Chunmei Zhang, Jinsong Wang, Songlin Wang","doi":"10.1177/20417314241280961","DOIUrl":"https://doi.org/10.1177/20417314241280961","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241280961"},"PeriodicalIF":6.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ROS in osteoclasts within the OA environment: A novel therapeutic strategy for osteoarthritis management.","authors":"Seungho Jeon, Tae Min Kim, Gitae Kwon, Junyoung Park, Sung Young Park, Seoung Hoon Lee, Eun-Jung Jin","doi":"10.1177/20417314241279935","DOIUrl":"10.1177/20417314241279935","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241279935"},"PeriodicalIF":6.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photocuring 3D printing technology as an advanced tool for promoting angiogenesis in hypoxia-related diseases.","authors":"Sang Yoon Lee, Huynh Dai Phuc, Soong Ho Um, Rosaire Mongrain, Jeong-Kee Yoon, Suk Ho Bhang","doi":"10.1177/20417314241282476","DOIUrl":"https://doi.org/10.1177/20417314241282476","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241282476"},"PeriodicalIF":6.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced interaction between genome-edited mesenchymal stem cells and platelets improves wound healing in mice.","authors":"De-Yong Li, Yu-Meng Li, Dan-Yi Lv, Tian Deng, Xin Zeng, Lu You, Qiu-Yu Pang, Yi Li, Bing-Mei Zhu","doi":"10.1177/20417314241268917","DOIUrl":"https://doi.org/10.1177/20417314241268917","url":null,"abstract":"<p><p>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 (<i>PSGL-1</i>) into the genome of human adipose-derived mesenchymal stem cells (ADSCs) using a Cas9-AAV6-based genome editing tool platform. Our findings revealed that <i>PSGL-1</i> knock-in enhanced the binding of ADSCs to platelets and their adhesion to the injured site. Moreover, the intravenous infusion of <i>PSGL-1</i> <i>-engineered</i> ADSCs (KI-ADSCs) significantly improved the homing efficiency and residence rate at the site of skin lesions in mice. Mechanistically, <i>PSGL-1</i> 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).</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241268917"},"PeriodicalIF":6.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascularized characteristics and functional regeneration of three-dimensional cell reconstruction of oral mucosa equivalents based on vascular homeostasis phenotypic modification.","authors":"Lijuan Shi, Yiwen Xu, Jingying Li, Li He, Kaiyu Li, Shigang Yin, Minhai Nie, Xuqian Liu","doi":"10.1177/20417314241268912","DOIUrl":"https://doi.org/10.1177/20417314241268912","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241268912"},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration.","authors":"Weilai Zhu, Jiaying Shi, Bowen Weng, Zhenger Zhou, Xufeng Mao, Senhao Pan, Jing Peng, Chi Zhang, Haijiao Mao, Mei Li, Jiyuan Zhao","doi":"10.1177/20417314241268189","DOIUrl":"10.1177/20417314241268189","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241268189"},"PeriodicalIF":6.7,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic three-dimensional coculture model: The future of tissue engineering applied to the peripheral nervous system.","authors":"William Choinière, Ève Petit, Vincent Monfette, Samuel Pelletier, Catherine Godbout-Lavoie, Marc-Antoine Lauzon","doi":"10.1177/20417314241265916","DOIUrl":"10.1177/20417314241265916","url":null,"abstract":"<p><p>Traumatic injuries to the peripheral nervous system (PNI) can lead to severe consequences such as paralysis. Unfortunately, current treatments rarely allow for satisfactory functional recovery. The high healthcare costs associated with PNS injuries, worker disability, and low patient satisfaction press for alternative solutions that surpass current standards. For the treatment of injuries with a deficit of less than 30 mm to bridge, the use of synthetic nerve conduits (NGC) is favored. However, to develop such promising therapeutic strategies, <i>in vitro</i> models that more faithfully mimic nerve physiology are needed. The absence of a clinically scaled model with essential elements such as a three-dimension environment and dynamic coculture has hindered progress in this field. The presented research focuses on the development of an <i>in vitro</i> coculture model of the peripheral nervous system (PNS) involving the use of functional biomaterial which microstructure replicates nerve topography. Initially, the behavior of neuron-derived cell lines (N) and Schwann cells (SC) in contact with a short section of biomaterial (5 mm) was studied. Subsequent investigations, using fluorescent markers and survival assays, demonstrated the synergistic effects of coculture. These optimized parameters were then applied to longer biomaterials (30 mm), equivalent to clinically used NGC. The results obtained demonstrated the possibility of maintaining an extended coculture of SC and N over a 7-day period on a clinically scaled biomaterial, observing some functionality. In the long term, the knowledge gained from this work will contribute to a better understanding of the PNS regeneration process and promote the development of future therapeutic approaches while reducing reliance on animal experimentation. This model can be used for drug screening and adapted for personalized medicine trials. Ultimately, this work fills a critical gap in current research, providing a transformative approach to study and advance treatments for PNS injuries.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241265916"},"PeriodicalIF":6.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of pH-sensitive nanoparticles loaded Celastrol targeting the inflammatory colons to treat ulcerative colitis.","authors":"Yue Zhao, Yinlian Yao, Shilong Fan, Xin Shen, Xingxing Chai, Zimin Li, Jiachun Zeng, Jiang Pi, Zhikun Zhou, Gonghua Huang, Hua Jin","doi":"10.1177/20417314241265892","DOIUrl":"10.1177/20417314241265892","url":null,"abstract":"<p><p>The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241265892"},"PeriodicalIF":6.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional vascularized liver organoid on extracellular matrix with defined stiffness for modeling fibrotic and normal tissues.","authors":"Lei Ma, Lin Yin, Hai Zhu, Jing Li, Dong Wang","doi":"10.1177/20417314241268344","DOIUrl":"10.1177/20417314241268344","url":null,"abstract":"<p><p>Antifibrotic drug screening requires evaluating the inhibitory effects of drug candidates on fibrotic cells while minimizing any adverse effects on normal cells. It is challenging to create organ-specific vascularized organoids that accurately model fibrotic and normal tissues for drug screening. Our previous studies have established methods for culturing primary microvessels and epithelial cells from adult tissues. In this proof-of-concept study, we used rats as a model organism to create a two-dimensional vascularized liver organoid model that comprised primary microvessels, epithelia, and stellate cells from adult livers. To provide appropriate substrates for cell culture, we engineered ECMs with defined stiffness to mimic the different stages of fibrotic tissues and normal tissues. We examined the effects of two TGFβ signaling inhibitors, A83-01 and pirfenidone, on the vascularized liver organoids on the stiff and soft ECMs. We found that A83-01 inhibited fibrotic markers while promoting epithelial genes of hepatocytes and cholangiocytes. However, it inhibited microvascular genes on soft ECM, indicating a detrimental effect on normal tissues. Furthermore, A83-01 significantly promoted the expression of markers of stem cells and cancers, increasing the potential risk of it being a carcinogen. In contrast, pirfenidone, an FDA-approved compound for antifibrotic treatments, did not significantly affect all the genes examined on soft ECM. Although pirfenidone had minor effects on most genes, it did reduce the expression of collagens, the major components of fibrotic tissues. These results explain why pirfenidone can slow fibrosis progression with minor side effects in clinical trials. In conclusion, our study presents a method for creating vascularized liver organoids that can accurately mimic fibrotic and normal tissues for drug screening. Our findings provide valuable insights into the potential risks and benefits of using A83-01 and pirfenidone as antifibrotic drugs. This method can be applied to other organs to create organ-specific vascularized organoids for drug development.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241268344"},"PeriodicalIF":6.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}