{"title":"基于DNA-SF水凝胶缓释系统的软骨类器官加速软骨再生。","authors":"Cong-Yi Shen, Qi-Rong Zhou, Xiang Wu, Xin-Yu Han, Qin Zhang, Xiao Chen, Yu-Xiao Lai, Long Bai, Ying-Ying Jing, Jian-Hua Wang, Cheng-Long Wang, Zhen Geng, Jia-Can Su","doi":"10.1186/s40779-025-00625-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cartilage repair remains a considerable challenge in regenerative medicine. Despite extensive research on biomaterials for cartilage repair in recent years, issues such as prolonged repair cycles and suboptimal outcomes persist. Organoids, miniature three-dimensional (3D) tissue structures derived from the directed differentiation of stem or progenitor cells, mimic the structure and function of natural organs. Therefore, the construction of cartilage organoids (COs) holds great promise as a novel strategy for cartilage repair.</p><p><strong>Methods: </strong>This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin (DNA-SF) hydrogel sustained-release system (DSRGT) with bone-marrow mesenchymal stem cells (BMSCs) to construct millimeter-scale cerebral organoids. COs at different developmental stages were characterized, and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.</p><p><strong>Results: </strong>This study developed a DSRGT by covalently grafting glucosamine (which promotes cartilage matrix synthesis) and TD-198946 (which promotes chondrogenic differentiation) onto a hydrogel using acrylic acid-polyethylene glycol-N-hydroxysuccinimide (AC-PEG-NHS). In vitro, 4-week COs exhibited higher SRY-box transcription factor 9 (SOX9), type II collagen (Col II), and aggrecan (ACAN) expression and lower type I collagen (Col I) and type X collagen (Col X) expression, indicating that 4 weeks is the optimal culture duration for hyaline cartilage development. In vivo, the mitogen-activated protein kinase (MAPK) signaling pathway was upregulated in 4-week COs, enabling cartilage repair within 8 weeks. Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.</p><p><strong>Conclusions: </strong>This study employs DSRGT to construct COs, providing an innovative strategy for the regeneration of cartilage defects.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"12 1","pages":"39"},"PeriodicalIF":22.9000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302690/pdf/","citationCount":"0","resultStr":"{\"title\":\"Accelerating cartilage regeneration with DNA-SF hydrogel sustained release system-based cartilage organoids.\",\"authors\":\"Cong-Yi Shen, Qi-Rong Zhou, Xiang Wu, Xin-Yu Han, Qin Zhang, Xiao Chen, Yu-Xiao Lai, Long Bai, Ying-Ying Jing, Jian-Hua Wang, Cheng-Long Wang, Zhen Geng, Jia-Can Su\",\"doi\":\"10.1186/s40779-025-00625-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cartilage repair remains a considerable challenge in regenerative medicine. Despite extensive research on biomaterials for cartilage repair in recent years, issues such as prolonged repair cycles and suboptimal outcomes persist. Organoids, miniature three-dimensional (3D) tissue structures derived from the directed differentiation of stem or progenitor cells, mimic the structure and function of natural organs. Therefore, the construction of cartilage organoids (COs) holds great promise as a novel strategy for cartilage repair.</p><p><strong>Methods: </strong>This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin (DNA-SF) hydrogel sustained-release system (DSRGT) with bone-marrow mesenchymal stem cells (BMSCs) to construct millimeter-scale cerebral organoids. COs at different developmental stages were characterized, and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.</p><p><strong>Results: </strong>This study developed a DSRGT by covalently grafting glucosamine (which promotes cartilage matrix synthesis) and TD-198946 (which promotes chondrogenic differentiation) onto a hydrogel using acrylic acid-polyethylene glycol-N-hydroxysuccinimide (AC-PEG-NHS). In vitro, 4-week COs exhibited higher SRY-box transcription factor 9 (SOX9), type II collagen (Col II), and aggrecan (ACAN) expression and lower type I collagen (Col I) and type X collagen (Col X) expression, indicating that 4 weeks is the optimal culture duration for hyaline cartilage development. In vivo, the mitogen-activated protein kinase (MAPK) signaling pathway was upregulated in 4-week COs, enabling cartilage repair within 8 weeks. Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.</p><p><strong>Conclusions: </strong>This study employs DSRGT to construct COs, providing an innovative strategy for the regeneration of cartilage defects.</p>\",\"PeriodicalId\":18581,\"journal\":{\"name\":\"Military Medical Research\",\"volume\":\"12 1\",\"pages\":\"39\"},\"PeriodicalIF\":22.9000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302690/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Military Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40779-025-00625-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Military Medical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40779-025-00625-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
背景：软骨修复在再生医学中仍然是一个相当大的挑战。尽管近年来对软骨修复的生物材料进行了广泛的研究，但修复周期延长和结果不理想等问题仍然存在。类器官是由干细胞或祖细胞定向分化而成的微型三维（3D）组织结构，模仿自然器官的结构和功能。因此，软骨类器官（COs）的构建作为一种新的软骨修复策略具有很大的前景。方法：采用数字光处理系统对dna -丝素（DNA-SF）水凝胶缓释系统（DSRGT）与骨髓间充质干细胞（BMSCs）进行生物3D打印，构建毫米级脑类器官。对不同发育阶段的COs进行表征，选择软骨表型最好的COs进行大鼠关节软骨缺损模型的体内软骨修复。结果：本研究将葡萄糖胺（促进软骨基质合成）和TD-198946（促进软骨分化）共价接枝到丙烯酸-聚乙二醇- n -羟基琥珀酰亚胺（AC-PEG-NHS）水凝胶上，制备了DSRGT。体外培养4周后，COs的SRY-box转录因子9 （SOX9）、II型胶原蛋白（Col II）和聚集蛋白（ACAN）表达较高，I型胶原蛋白（Col I）和X型胶原蛋白（Col X）表达较低，表明4周是透明软骨发育的最佳培养时间。在体内，丝裂原活化蛋白激酶（MAPK）信号通路在4周的COs中上调，使软骨在8周内修复。转录组学分析显示，4周COs再生软骨的基因表达谱与健康软骨相似。结论：本研究采用DSRGT构建软骨组织，为软骨缺损的再生提供了一种创新的策略。
Background: Cartilage repair remains a considerable challenge in regenerative medicine. Despite extensive research on biomaterials for cartilage repair in recent years, issues such as prolonged repair cycles and suboptimal outcomes persist. Organoids, miniature three-dimensional (3D) tissue structures derived from the directed differentiation of stem or progenitor cells, mimic the structure and function of natural organs. Therefore, the construction of cartilage organoids (COs) holds great promise as a novel strategy for cartilage repair.
Methods: This study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin (DNA-SF) hydrogel sustained-release system (DSRGT) with bone-marrow mesenchymal stem cells (BMSCs) to construct millimeter-scale cerebral organoids. COs at different developmental stages were characterized, and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.
Results: This study developed a DSRGT by covalently grafting glucosamine (which promotes cartilage matrix synthesis) and TD-198946 (which promotes chondrogenic differentiation) onto a hydrogel using acrylic acid-polyethylene glycol-N-hydroxysuccinimide (AC-PEG-NHS). In vitro, 4-week COs exhibited higher SRY-box transcription factor 9 (SOX9), type II collagen (Col II), and aggrecan (ACAN) expression and lower type I collagen (Col I) and type X collagen (Col X) expression, indicating that 4 weeks is the optimal culture duration for hyaline cartilage development. In vivo, the mitogen-activated protein kinase (MAPK) signaling pathway was upregulated in 4-week COs, enabling cartilage repair within 8 weeks. Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.
Conclusions: This study employs DSRGT to construct COs, providing an innovative strategy for the regeneration of cartilage defects.
期刊介绍：
Military Medical Research is an open-access, peer-reviewed journal that aims to share the most up-to-date evidence and innovative discoveries in a wide range of fields, including basic and clinical sciences, translational research, precision medicine, emerging interdisciplinary subjects, and advanced technologies. Our primary focus is on modern military medicine; however, we also encourage submissions from other related areas. This includes, but is not limited to, basic medical research with the potential for translation into practice, as well as clinical research that could impact medical care both in times of warfare and during peacetime military operations.
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