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骨骼干细胞动力学及其在老年骨质疏松症钛植入物设计中的潜在应用研究。

A Study of Skeletal Stem Cell Dynamics and Its Potential Applications in the Design of a Titanium Implant for Senile Osteoporosis.

作者信息

Fan Wuzhe, Zheng Tao, Mao Mingsong, Gao Pengfei, Yang Yulu, Wang Rong, Yang Yao, Zuo Yangpeng, Yuan Tiantian, Bai Ruqing, Yang Weihu, Yan Xingchen, Cai Kaiyong

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, China.

School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.

出版信息

Adv Sci (Weinh). 2025 Sep;12(34):e06982. doi: 10.1002/advs.202506982. Epub 2025 Jun 19.

DOI:10.1002/advs.202506982
PMID:40536323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12442682/
Abstract

Traditional biomaterial design often prioritizes empirical knowledge over disease mechanisms and pathological dynamics, resulting in imprecise solutions in complex clinical conditions. Age-related osteoporosis (A-OP) is a disease associated with aging, characterized by a dysfunctional pathological microenvironment that hinders the osseointegration of conventional titanium implants. To develop a targeted titanium implant for A-OP, rat single-cell transcriptomics is integrated with human serum-derived transcriptome data to investigate dynamic changes in skeletal stem cells (SSCs) during aging, which guided the implant design. These findings reveal that hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) within SSCs interact via a feedback loop: HSCs undergo premature senescence, leading to depletion of HSCs and secondary senescence of MSCs. Senescent MSCs exhibit adipogenic bias, perpetuating the pathological cycle of A-OP. Using core genes identified in the transcriptome analyses, resveratrol is selected and utilized it and a GelMA-chitosan hydrogel to decorate titanium implants for localized delivery. In the A-OP microenvironment, the hydrogel enables sustained responsive release of resveratrol, which reverses MSC senescence and redirects differentiation from adipogenic to osteogenic lineages, thereby breaking the pathological cycle. This multi-omics-driven implant design enhances precision and offers a novel methodology for biomaterial development.

摘要

传统的生物材料设计往往将经验知识置于疾病机制和病理动态之上，导致在复杂临床情况下的解决方案不够精确。年龄相关性骨质疏松症（A-OP）是一种与衰老相关的疾病，其特征在于病理微环境功能失调，这会阻碍传统钛植入物的骨整合。为了开发针对A-OP的靶向钛植入物，将大鼠单细胞转录组学与人类血清衍生的转录组数据相结合，以研究衰老过程中骨骼干细胞（SSCs）的动态变化，从而指导植入物设计。这些发现表明，SSCs中的造血干细胞（HSCs）和间充质干细胞（MSCs）通过反馈回路相互作用：HSCs过早衰老，导致HSCs耗竭和MSCs继发性衰老。衰老的MSCs表现出成脂倾向，使A-OP的病理循环持续存在。利用转录组分析中确定的核心基因，选择白藜芦醇并将其与GelMA-壳聚糖水凝胶一起用于修饰钛植入物以实现局部递送。在A-OP微环境中，水凝胶能够持续响应释放白藜芦醇，从而逆转MSC衰老并将分化从成脂谱系重定向到成骨谱系，从而打破病理循环。这种多组学驱动的植入物设计提高了精度，并为生物材料开发提供了一种新方法。

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Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.
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