Wenyi Zheng , Li Ma , Xueshi Luo , Renhao Xu , Zhiying Cao , Yanni He , Yanzhou Chang , Yuanyuan You , Tianfeng Chen , Hongmei Liu
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引用次数: 0
摘要
骨间充质干细胞(BMSCs)在骨再生的炎症期和修复期的物理和化学特性导致其功能失调,是骨再生失败的原因之一。为了满足 BMSCs 在不同阶段的时空需求,设计能对外界刺激做出反应的生物相容性材料,改善 BMSCs 在炎症阶段的迁移、减少增殖阶段的凋亡以及扫清分化阶段的障碍,是多阶段修复骨缺损的有效策略。在这项研究中,我们设计了一种级联反应功能复合水凝胶(Gel@Eb/HA)来调节 BMSCs 在体外和体内的功能障碍。在炎症阶段,Gel@Eb/HA通过上调趋化因子(C-C基序)配体5(CCL5)的表达改善了BMSCs的迁移。超声波(US)可引发依布硒的快速释放,从而消除活性氧(ROS)在BMSCs中的积累,并逆转氧化应激下的细胞凋亡。持续的 US 处理加速了材料的降解,从而为 BMSCs 的成骨分化提供了 Ca2+。总之,我们的研究凸显了由 US 控制的智能系统的前景,它为解决多阶段骨修复的复杂性提供了一种新策略。
Ultrasound-triggered functional hydrogel promotes multistage bone regeneration
The dysfunction of bone mesenchymal stem cells (BMSCs), caused by the physical and chemical properties of the inflammatory and repair phases of bone regeneration, contributes to the failure of bone regeneration. To meet the spatiotemporal needs of BMSCs in different phases, designing biocompatible materials that respond to external stimuli, improve migration in the inflammatory phase, reduce apoptosis in the proliferative phase, and clear the hurdle in the differentiation phase of BMSCs is an effective strategy for multistage repair of bone defects. In this study, we designed a cascade-response functional composite hydrogel (Gel@Eb/HA) to regulate BMSCs dysfunction in vitro and in vivo. Gel@Eb/HA improved the migration of BMSCs by upregulating the expression of chemokine (C–C motif) ligand 5 (CCL5) during the inflammatory phase. Ultrasound (US) triggered the rapid release of Ebselen (Eb), eliminating the accumulation of reactive oxygen species (ROS) in BMSCs, and reversing apoptosis under oxidative stress. Continued US treatment accelerated the degradation of the materials, thereby providing Ca2+ for the osteogenic differentiation of BMSCs. Altogether, our study highlights the prospects of US-controlled intelligent system, that provides a novel strategy for addressing the complexities of multistage bone repair.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.