Xu Lou , Fuxiao Wang , Xukun Lv , Dan Huang , Yan Hu , Hao Zhang , Xiao Chen , Yuxiao Lai , Yingying Jing , Jianhua Wang , Long Bai , Jiacan Su , Hua Yue
{"title":"通过时空分级水凝胶的顺序血管生成-成骨耦合使血管化骨类器官能够用于临界大小的颅骨缺损重建","authors":"Xu Lou , Fuxiao Wang , Xukun Lv , Dan Huang , Yan Hu , Hao Zhang , Xiao Chen , Yuxiao Lai , Yingying Jing , Jianhua Wang , Long Bai , Jiacan Su , Hua Yue","doi":"10.1016/j.compositesb.2025.112553","DOIUrl":null,"url":null,"abstract":"<div><div>While bone organoids show potential in mimicking native bone microenvironments, their clinical translation is hindered by insufficient vascularization in large cellular aggregates. We present a spatiotemporally graded hydrogel system enabling sequential angiogenic-osteogenic coupling to achieve functional vascularization of bone organoids. The system integrates a gelatin methacryloyl (GelMA) matrix encapsulating mesenchymal/endothelial cells and dimethyloxalylglycine (DMOG) with silk fibroin microspheres loaded with nano-hydroxyapatite (nHAp). By leveraging differential degradation kinetics, rapid GelMA dissolution coordinates with DMOG release to initiate prevascular networks for metabolic support, while sustained silk fibroin degradation enables nHAp-mediated osteogenic maturation. Dynamic culture over 21 days demonstrated spatiotemporal synchronization of vascular perfusion and bone matrix deposition, overcoming vascularization limitations in organoid scaling. In critical-sized calvarial defects, this sequential coupling strategy achieved significantly greater bone regeneration compared to static scaffolds, with functional microvascular integration. This spatiotemporally graded hydrogel platform establishes a paradigm for engineering metabolically active bone organoids, advancing hierarchical tissue reconstruction strategies.</div></div>","PeriodicalId":10660,"journal":{"name":"Composites Part B: Engineering","volume":"302 ","pages":"Article 112553"},"PeriodicalIF":12.7000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sequential angiogenic-osteogenic coupling via a spatiotemporally graded hydrogel enables vascularized bone organoids for critical-sized calvarial defect reconstruction\",\"authors\":\"Xu Lou , Fuxiao Wang , Xukun Lv , Dan Huang , Yan Hu , Hao Zhang , Xiao Chen , Yuxiao Lai , Yingying Jing , Jianhua Wang , Long Bai , Jiacan Su , Hua Yue\",\"doi\":\"10.1016/j.compositesb.2025.112553\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>While bone organoids show potential in mimicking native bone microenvironments, their clinical translation is hindered by insufficient vascularization in large cellular aggregates. We present a spatiotemporally graded hydrogel system enabling sequential angiogenic-osteogenic coupling to achieve functional vascularization of bone organoids. The system integrates a gelatin methacryloyl (GelMA) matrix encapsulating mesenchymal/endothelial cells and dimethyloxalylglycine (DMOG) with silk fibroin microspheres loaded with nano-hydroxyapatite (nHAp). By leveraging differential degradation kinetics, rapid GelMA dissolution coordinates with DMOG release to initiate prevascular networks for metabolic support, while sustained silk fibroin degradation enables nHAp-mediated osteogenic maturation. Dynamic culture over 21 days demonstrated spatiotemporal synchronization of vascular perfusion and bone matrix deposition, overcoming vascularization limitations in organoid scaling. In critical-sized calvarial defects, this sequential coupling strategy achieved significantly greater bone regeneration compared to static scaffolds, with functional microvascular integration. This spatiotemporally graded hydrogel platform establishes a paradigm for engineering metabolically active bone organoids, advancing hierarchical tissue reconstruction strategies.</div></div>\",\"PeriodicalId\":10660,\"journal\":{\"name\":\"Composites Part B: Engineering\",\"volume\":\"302 \",\"pages\":\"Article 112553\"},\"PeriodicalIF\":12.7000,\"publicationDate\":\"2025-04-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Composites Part B: Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1359836825004548\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Composites Part B: Engineering","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1359836825004548","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, MULTIDISCIPLINARY","Score":null,"Total":0}
Sequential angiogenic-osteogenic coupling via a spatiotemporally graded hydrogel enables vascularized bone organoids for critical-sized calvarial defect reconstruction
While bone organoids show potential in mimicking native bone microenvironments, their clinical translation is hindered by insufficient vascularization in large cellular aggregates. We present a spatiotemporally graded hydrogel system enabling sequential angiogenic-osteogenic coupling to achieve functional vascularization of bone organoids. The system integrates a gelatin methacryloyl (GelMA) matrix encapsulating mesenchymal/endothelial cells and dimethyloxalylglycine (DMOG) with silk fibroin microspheres loaded with nano-hydroxyapatite (nHAp). By leveraging differential degradation kinetics, rapid GelMA dissolution coordinates with DMOG release to initiate prevascular networks for metabolic support, while sustained silk fibroin degradation enables nHAp-mediated osteogenic maturation. Dynamic culture over 21 days demonstrated spatiotemporal synchronization of vascular perfusion and bone matrix deposition, overcoming vascularization limitations in organoid scaling. In critical-sized calvarial defects, this sequential coupling strategy achieved significantly greater bone regeneration compared to static scaffolds, with functional microvascular integration. This spatiotemporally graded hydrogel platform establishes a paradigm for engineering metabolically active bone organoids, advancing hierarchical tissue reconstruction strategies.
期刊介绍:
Composites Part B: Engineering is a journal that publishes impactful research of high quality on composite materials. This research is supported by fundamental mechanics and materials science and engineering approaches. The targeted research can cover a wide range of length scales, ranging from nano to micro and meso, and even to the full product and structure level. The journal specifically focuses on engineering applications that involve high performance composites. These applications can range from low volume and high cost to high volume and low cost composite development.
The main goal of the journal is to provide a platform for the prompt publication of original and high quality research. The emphasis is on design, development, modeling, validation, and manufacturing of engineering details and concepts. The journal welcomes both basic research papers and proposals for review articles. Authors are encouraged to address challenges across various application areas. These areas include, but are not limited to, aerospace, automotive, and other surface transportation. The journal also covers energy-related applications, with a focus on renewable energy. Other application areas include infrastructure, off-shore and maritime projects, health care technology, and recreational products.