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蜂窝状仿生氧化石墨烯量子点/层状双氢氧化物复合纳米涂层通过激活线粒体自噬促进骨质疏松性骨再生。

Honeycomb Bionic Graphene Oxide Quantum Dot/Layered Double Hydroxide Composite Nanocoating Promotes Osteoporotic Bone Regeneration via Activating Mitophagy.

作者信息

Li Dan, Dai Danni, Wang Jianrong, Zhang Chao

机构信息

Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, China.

出版信息

Small. 2024 Dec;20(50):e2403907. doi: 10.1002/smll.202403907. Epub 2024 Sep 30.

DOI:10.1002/smll.202403907
PMID:39344577
Abstract

Abnormal osteogenic and remodeling microenvironment due to osteoblast apoptosis are the primary causes of delayed fracture healing in osteoporotic patients. Magnesium (Mg) alloys exhibit biodegradability and appropriate elastic moduli for bone defects in osteoporosis, but the effect on the local bone remodeling disorder is still insufficient. Inspired by the "honeycomb," layered double hydroxide (LDH) with regular traps with graphene oxide quantum dots (GOQDs) inlayed is constructed by pulsed electrodeposition to generate GOQD/LDH composite nanocoatings on the surfaces of Mg alloy substrates. The honeycomb bionic multi-layer stereoscopic structure shows good regulation of the degradation of Mg alloy for the support of healing time required for osteoporotic bone defect. Within its lattice, the local microenvironment conducive to osteogenesis is provided by both the rescue effect of GOQD and LDH. The osteoblast apoptosis is rescued due to the activation of mitophagy to clear dysfunctional mitochondria, where the upregulation of BNIP3 phosphorylation played a key role. The osteoporotic rat model of femoral defects confirmed the improvement of bone regeneration and osseointegration of GOQD/LDH coating. In summary, honeycomb bionic composite nanocoatings with controllable degradation and excellent pro-osteogenic performance demonstrated a promising design strategy on Mg alloy implants in the therapy of osteoporotic bone defects.

摘要

成骨细胞凋亡导致的异常成骨和重塑微环境是骨质疏松症患者骨折愈合延迟的主要原因。镁(Mg)合金具有生物可降解性和适合骨质疏松症骨缺损的弹性模量,但其对局部骨重塑紊乱的影响仍不充分。受“蜂窝”启发,通过脉冲电沉积构建了具有嵌入氧化石墨烯量子点(GOQDs)的规则陷阱的层状双氢氧化物(LDH),以在镁合金基底表面生成GOQD/LDH复合纳米涂层。蜂窝状仿生多层立体结构对镁合金的降解具有良好的调控作用,以支持骨质疏松性骨缺损所需的愈合时间。在其晶格内,GOQD和LDH的挽救作用共同提供了有利于成骨的局部微环境。由于线粒体自噬被激活以清除功能失调的线粒体,成骨细胞凋亡得到挽救,其中BNIP3磷酸化的上调起关键作用。股骨缺损的骨质疏松大鼠模型证实了GOQD/LDH涂层对骨再生和骨整合的改善作用。总之,具有可控降解和优异促骨生成性能的蜂窝状仿生复合纳米涂层为治疗骨质疏松性骨缺损的镁合金植入物提供了一种有前景的设计策略。

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