CGRP‐Loaded Porous Microspheres Protect BMSCs for Alveolar Bone Regeneration in the Periodontitis Microenvironment

Abstract Periodontitis is a prevalent dental disease marked by progressive destruction of tooth‐supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell‐based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene‐related peptide (CGRP)‐loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP can effectively ameliorate the inflammation‐induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD‐, LRR‐, and pyrin domain‐containing protein 3)/Caspase‐1 (CASP1) pathway. Moreover, the porous architecture of PMs provides effective cell‐carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC‐loaded PMs can effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell‐mediated tissue regeneration and repair under inflammatory conditions.