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

IF 12.7 1区 材料科学 Q1 ENGINEERING, MULTIDISCIPLINARY
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
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引用次数: 0

摘要

虽然骨类器官显示出模仿天然骨微环境的潜力,但它们的临床转化受到大细胞聚集体血管化不足的阻碍。我们提出了一个时空分级的水凝胶系统,使顺序血管生成-成骨耦合实现骨类器官的功能性血管化。该系统集成了凝胶甲基丙烯酰(GelMA)基质包裹间充质/内皮细胞和二甲基氧基酰甘氨酸(DMOG),丝素微球装载纳米羟基磷灰石(nHAp)。通过利用差异降解动力学,GelMA快速溶解与DMOG释放协调,启动血管前网络以支持代谢,而持续的丝素降解使nhap介导的成骨成熟成为可能。超过21天的动态培养表明血管灌注和骨基质沉积的时空同步,克服了类器官尺度的血管化限制。在临界尺寸的颅骨缺损中,与静态支架相比,这种顺序耦合策略实现了更大的骨再生,并具有功能性微血管整合。这种时空分级的水凝胶平台为工程代谢活性骨类器官建立了一个范例,推进了分层组织重建策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
Composites Part B: Engineering
Composites Part B: Engineering 工程技术-材料科学:复合
CiteScore
24.40
自引率
11.50%
发文量
784
审稿时长
21 days
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.
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