文献类型：期刊文献

英文题名：A sustained NAD+ supplementation-biosynthesis nanoplatform for metabolic restoration in aged bone regeneration

作者：Xie, Fangru[1,2];He, Zirui[1,2];Xu, Shiyu[1,3];Bai, Xiaoqiao[1];Wang, Xuan[1,2];Zhang, Fan[1];Yuan, Yuan[1,2];Liu, Changsheng[1,2];Niu, Dechao[1,3]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Natl Nat Sci Fdn China, Excellent Res Grp Project, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Frontier Sci Ctr Mat Biol & Dynam Chem, Shanghai Engn Res Ctr Hierarch Nanomat, Low Dimens Mat Chem Lab, Shanghai 200237, Peoples R China

年份：2026

卷号：64

起止页码：781

外文期刊名：BIOACTIVE MATERIALS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001803294000001)】；

基金：The authors wish to express their gratitude to the financial support from the Excellent Research Group Project of National Natural Science Foundation of China (No. T2288102), Joint Fund of the National Natural Science Foundation of China for Regional Innovation and Development (No. U24A20376), National Natural Science Foundation of China (Nos. 32371406, 32271401), National Key Research and Development Program of China (No. 2022YFC2405702).

语种：英文

外文关键词：NAD(+) metabolism; Dual-mesoporous silica; Hydrogel; Cellular senescence; Aged bone regeneration

摘要：Increasing NAD+ levels has demonstrated promising therapeutic potential for treating aging-related skeletal disorders. However, for existing bone defects in aged individuals, it remains a formidable challenge to achieve localized and sustained NAD+ restoration while overcoming poor NAD+ delivery efficiency and impaired endogenous biosynthesis in senescent cells. Herein, this study developed a sustained NAD+ supplementationbiosynthesis nanoplatform, N/S@M@P, to stimulate aged bone regeneration. This platform employs dualmesoporous silica nanoparticles to highly load NAD+ and controllably load NAD+ biosynthesis activator, establishing a "supplementation-biosynthesis" strategy for rapid NAD+ replenishment and sustained NAD+ metabolic restoration in senescent bone marrow-derived mesenchymal stromal cells (BMSCs). Meanwhile, N/ S@M enhanced cellular uptake efficiency by 41.0% through regulating the endocytic pathways of senescent BMSCs. After incorporation into an injectable hydrogel scaffold, N/S@M@P enabled sustained particle release over 14 days, supporting prolonged metabolic restoration. This strategy increased the NAD+/NADH ratio by 11.2-fold and increased ATP production by 3.25-fold in senescent BMSCs. In aged bone defects, N/S@M@P reduced the proportion of senescent BMSCs to 21.2% at day 7 and increased the bone volume fraction (BV/TV) by 119% at 4 weeks. These findings demonstrate that this nanoplatform can effectively restore the functions of senescent BMSCs, providing a promising therapeutic strategy for aging-related bone regeneration.