Remodeling the Senescent Microenvironment for Promoting Osteoporotic Tendon-to-Bone Healing via Synergizing Senolytic Quercetin and Aligned Nanowire-Structured Hydrogels
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Le résumé fourni par la source
Osteoporotic tendon-to-bone healing remains a major challenge, as cellular senescence disrupts tissue regeneration and impairs repair outcomes. Although the role of cellular senescence in rotator cuff repair is increasingly recognized, current strategies often overlook the complex pathological context, particularly the dual impacts of senescence on both bone marrow-derived mesenchymal stem cells (BMSCs) and tendon-derived stem cells (TDSCs). This gap hampers effective tendon-to-bone healing and integration, especially under osteoporotic conditions. Herein, a composite hydrogel system, quercetin-loaded aligned ultralong hydroxyapatite nanowire/gelatin-hyaluronic acid hydrogel (Que-AHNW/GH), has been developed to address these challenges. By integrating senolytic quercetin as a biological cue with highly aligned ultralong hydroxyapatite (HAP) nanowires as a topographical cue, the system remodels the senescent microenvironment, alleviating senescence in both BMSCs and TDSCs and promoting osteogenesis and tenogenesis. Que-AHNW/GH suppresses the PI3K/AKT pathway, enhances autophagy, and reduces senescence in both cell types. In vivo, Que-AHNW/GH improves bone tunnel regeneration, tendon repair, and tendon-to-bone integration in osteoporotic rats with rotator cuff injury. This system enhances biomechanical strength and gait performance and demonstrates excellent biosafety. These findings highlight the promising potential of Que-AHNW/GH as a multifunctional biomaterial for effectively promoting senescence-related tendon-to-bone healing, offering a promising solution for treating osteoporotic tendon-to-bone injuries.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Remodeling the Senescent Microenvironment for Promoting Osteoporotic Tendon-to-Bone Healing via Synergizing Senolytic Quercetin and Aligned Nanowire-Structured Hydrogels
- Date Crossref
- 06/05/2025
- Éditeur
- American Chemical Society (ACS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Shanghai Jiao Tong University pays non établi dans la noticeUniversité ou école supérieure
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Shanghai Sixth People's Hospital pays non établi dans la noticeÉtablissement de santé
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Chinese Academy of Sciences pays non établi dans la noticeOrganisme public
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Shanghai Institute of Ceramics pays non établi dans la noticeStructure de recherche
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Department of Orthopedic Surgery pays non établi dans la noticeInstitution
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State Key Laboratory of High Performance Ceramics and Superfine Microstructure pays non établi dans la noticeStructure de recherche
Shanghai Jiao Tong University, Shanghai Sixth People's Hospital et Chinese Academy of Sciences, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.