Orchestrated Engineered Polyphenol-Peptide Condensates Coupled With β-GP Reverses Diabetic Osteoporosis by Remodeling Mitophagy

  • Adv Sci (Weinh). 2026 May 12:e75666. doi: 10.1002/advs.75666.
Xiuyun Xu  1  2 ,  Meiqin Zhang  1  2 ,  Ting Wu  3  2 ,  Erfan Wei  1  2 ,  Andrei Y Hancharou  4 ,  Zeying Wang  1  2 ,  Zijuan Wang  3  2 ,  Letian Lv  3  2 ,  Likun Wu  1  2 ,  Xingtong Pan  1  2 ,  Qiyue Zhu  1  2 ,  Xinyi Dong  1  2 ,  Hao Liu  3  2 ,  Yongsheng Zhou  1  2
Affiliations
  • 1. Department of Prosthodontics, Peking University School of Stomatology, Beijing, China.
  • 2. National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory for Intelligent Biomanufacturing and Regeneration of Craniofacial Tissues, Beijing Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Beijing, China.
  • 3. The Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
  • 4. Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, Minsk, Republic of Belarus.
PMID: 42118233 DOI: 10.1002/advs.75666
Abstract

Diabetic osteoporosis (DOP) is a chronic complication of diabetes mellitus characterized by reduced bone mass, disrupted microarchitecture, and an elevated fracture risk. Persistent oxidative stress and inflammation further inhibit osteogenesis and angiogenesis, accelerating bone degeneration. In this study, we used a peptide-polyphenol conjugation strategy to develop a multifunctional colloidal nanoplatform (β-GP@EGCG-E7). The bone-targeting peptide E7 was covalently conjugated with epigallocatechin-3- gallate (EGCG) and subsequently loaded with β-glycerophosphate (β-GP). Sequentially, this nanoplatform integrates bone-targeted delivery, improving mitochondrial quality by anti-inflammation and antioxidation, as well as osteogenesis and angiogenesis within a single system. In detail, in a high glucose microenvironment, the nanoplatform selectively accumulates in bone lesions, scavenges excess intracellular Reactive Oxygen Species (ROS) triggered by high glucose, clears damaged mitochondria by activating PINK1-Parkin mediated Mitophagy, and exerts anti-inflammatory effects to rebalance the microenvironment of bone regeneration. Concurrently, sustained phosphate release supports mineralization, promotes osteogenic differentiation, enhances angiogenesis, and improves local microcirculation. In diabetic osteoporotic models, β-GP@EGCG-E7 significantly reduced oxidative stress, restored mitochondrial homeostasis, and promoted bone and vascular regeneration. This study provides a promising therapeutic strategy for DOP and highlights the potential of peptide-polyphenol hybrid nanomaterials for regenerative applications.

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