Local Elimination of Senescent Cells Promotes Bone Defect Repair during Aging

Area of Science:

• Gerontology
• Regenerative Medicine
• Biomaterials Science

Background:

• Aging impairs bone marrow mesenchymal stem cells (BMSCs), hindering bone defect repair in the elderly.
• Senescent cell elimination is a potential strategy for age-related diseases, but its role in elderly bone regeneration is unclear.

Purpose of the Study:

• To investigate if local elimination of senescent BMSCs can enhance bone regeneration in aged individuals.
• To develop a senolytic hydrogel for targeted delivery of quercetin to senescent BMSCs.

Main Methods:

• Screening and validation of senolytics for BMSCs, identifying quercetin as optimal.
• Development of a microenvironment-responsive hydrogel encapsulating quercetin.
• In vitro and in vivo assessment of quercetin-loaded hydrogel's efficacy in clearing senescent cells and promoting bone repair in old rats.

Main Results:

• Quercetin effectively eliminated senescent BMSCs in vitro, restoring their self-renewal and osteogenic capacity.
• The quercetin-loaded hydrogel demonstrated controlled release in response to senescence-associated MMPs.
• In vivo, the hydrogel cleared local senescent cells, reduced MMPs, and significantly accelerated bone defect repair in aged rats.

Conclusions:

• Targeted elimination of senescent BMSCs is a viable strategy for enhancing bone regeneration in aged individuals.
• A novel quercetin-loaded, microenvironment-responsive hydrogel offers a promising therapeutic approach for age-related bone defects.