Abstract
Guided tissue regeneration (GTR), which is based on creating a physical barrier to prevent the downgrowth of epithelial and connective tissues into the defect site, has been widely used in clinical practice for periodontal regeneration for many years. However, its outcomes remain variable due to highly specific indications, the demand for proficient surgical skills, and frequent occurrence of complications. In this study, we developed a new GTR biomaterial that acts as a biological barrier for epithelial cells and fibroblasts while also serving as a scaffold for bone marrow-derived mesenchymal stem cells (BMSCs) and periodontal ligament stem cells (PDLSCs). This innovative GTR biomaterial is bioinspired injectable microspheres that are self-assembled from nanofibers, and their surfaces are conjugated with E7, a short peptide that selectively promotes BMSC and PDLSC adhesion but inhibits the attachment and spreading of epithelial cells and gingival fibroblasts. The selective affinity afforded by E7 on the surfaces of the nanofibrous microspheres facilitated the colonization of BMSCs in the periodontal defect, thereby substantially improving functional periodontal regeneration, as evidenced by enhanced new bone formation, reduced root exposure, and diminished attachment loss. The remarkable superiority of the bioinspired microspheres over conventional GTR materials in promoting periodontal regeneration underscores the potential of this innovative approach to enhance the efficacy of functional periodontal tissue regeneration.