This study presents the first application of the PROTAC system in the field of regenerative medicine. We systematically designed and synthesized a library of MDM2-targeting PROTACs and evaluated their degradation potency. The newly developed MDM2-PROTACs effectively degraded the target protein and significantly enhanced osteogenic differentiation. Their bone regeneration potential was demonstrated in various preclinical models. Notably, the combination of MDM2-PROTACs with bisphosphonates produced a synergistic effect, highlighting the therapeutic potential of PROTACs in bone regeneration.

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