巨噬细胞膜仿生包覆纳米颗粒的水凝胶递送系统对成骨活性及大鼠颅骨愈合的增强效应OA
Enhanced effect of macrophage membrane-mimetic nanoparticle-coated hydrogel delivery on osteogenesis and rat cranial healing
目的 开发一种新型纳米水凝胶骨修复系统,通过将姜黄素(Curcumin)载入二氧化硅纳米颗粒(SiO2),包覆巨噬细胞膜(MM),并嵌入甲基丙烯酰化明胶(GelMA)水凝胶,构建兼具药物缓释、仿生靶向和三维多孔结构的巨噬细胞膜包覆载药二氧化硅的复合水凝胶(CS@M-GelMA),以解决姜黄素生物利用度低、传统材料成骨诱导性不足的问题,实现骨缺损的高效再生.方法 通过扫描电镜(SEM)和能谱分析(EDS)表征材料形貌与元素组成.体外实验根据水凝胶的不同分为GelMA、S-GelMA、CS-GelMA及CS@M-GelMA四组,并评估各组水凝胶对MC3T3-E1细胞增殖(CCK-8、活/死细胞染色)、成骨分化(ALP/ARS染色)及成骨基因(RUNX2、BMP、OPN)表达的影响.体内实验根据植入水凝胶类型的不同,将6周SD大鼠随机分为GelMA、CS-GelMA以及CS@M-GelMA三组(10只/组),并构建颅骨缺损模型(直径5 mm).利用Micro-CT分析骨再生效果(BV/TV、BMD),并通过HE染色验证生物安全性.结果 SEM和EDS证实CS@M纳米颗粒的合成,SEM显示CS@M-GelMA水凝胶具有均匀多孔结构.CS@M-GelMA组细胞活性显著优于对照组(P<0.000 1),ALP与ARS染色的定量值显著高于对照组(P<0.000 1),成骨基因(R U N X 2、B M P、O P N)表达上调2~3倍(P<0.000 1).Micro-CT显示CS@M-GelMA组4周后的BV/TV和BMD均显著高于对照组(P<0.001),且主要器官无毒性反应.结论 CS@M-GelMA水凝胶通过细胞膜修饰增强靶向性,二氧化硅纳米颗粒实现姜黄素缓释,GelMA提供三维支持,协同促进成骨分化与骨再生.其多孔结构、优异生物相容性及促成骨活性,为临床骨缺损修复提供了兼具高效性与安全性的新策略.
Objective To develop a novel nanohydrogel bone repair system by loading curcumin into silica nanoparticles(SiO2),coating them with macrophage membranes(MM),and embedding them in methacryloylated gelatin(GelMA)hydrogels.This new composite hydrogel,termed CS@M-GelMA,combines drug sustained release,biomimetic targeting,and a three-dimensional porous structure to address the issues of curcumin's low bioavailability and the insufficient osteogenic induction of traditional materials,thereby achieving efficient regeneration of bone defects.Methods Material morphology and elemental composition were characterized through scanning electron microscopy(SEM)and energy-dispersive spectroscopy(EDS).In vitro experiments were divided into four groups:GelMA,S-GelMA,CS-GelMA and CS@M-GelMA,and the effects of each hydrogel on MC3T3-E1 cell proliferation(CCK-8,live/dead staining),osteogenic differentiation(ALP/ARS staining),and osteogenic gene(RUNX2,BMP2,OPN)expression were evaluated.For in vivo studies,6-week-old SD rats were randomly divided into 3 groups(GelMA,CS-GelMA and CS@M-GelMA,10 rats/group)based on implanted hydrogel type,with a 5 mm-diameter calvarial defect model established.Micro-CT analyzed bone regeneration efficacy(BV/TV,BMD),and HE staining verified biosafety.Results SEM and EDS confirmed the synthesis of CS@M nanoparticles,with SEM revealing a uniform porous structure in CS@M-GelMA hydrogels.The CS@M-GelMA group exhibited significantly higher cell viability compared to the control group(P<0.000 1),while the quantitative values of ALP and ARS staining were significantly elevated(P<0.000 1),and the expression of osteogenic genes(R U N X 2,B M P,O P N)increased 2-3 times(P<0.000 1).Micro-CT analysis indicated that after 4 weeks,both BV/TV and BMD in the CS@M-GelMA group were significantly higher than in the control group(P<0.001),with no toxic reactions observed in major organs.Conclusion The CS@M-GelMA hydrogel enhances targeting through cellular membrane modification,facilitates the sustained release of curcumin via silica nanoparticles,and provides three-dimensional support with GelMA,collectively promoting osteogenic differentiation and bone regeneration.Its porous structure,excellent biocompatibility,and osteogenic activity offer a safe and effective new strategy for clinical bone defect repair.
王国俊;胡桑;魏任雄
天门市第一人民医院创伤外科,湖北 天门,431700||武汉大学中南医院脊柱与骨肿瘤科,湖北 武汉,430071武汉大学中南医院脊柱与骨肿瘤科,湖北 武汉,430071武汉大学中南医院脊柱与骨肿瘤科,湖北 武汉,430071
医药卫生
骨植入材料姜黄素二氧化硅纳米颗粒细胞膜成骨诱导活性
Bone implant materialsCurcuminSilica nanoparticlesCell membraneOsteoinductive activity
《生物骨科材料与临床研究》 2026 (2)
1-8,8
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