Amelogenin-Derived Peptide-Modified Poly(amidoamine) Dendrimers for Root Caries Prevention

Root caries present a significant challenge in dentistry. The unsatisfactory prognosis of restorative treatments requires novel, noninvasive preventive strategies. Here, we developed an amelogenin-derived peptide-modified poly(amidoamine), PAMAM-C11, to prevent demineralization in caries lesions and control periodontal destruction. PAMAM can induce dentin remineralization, whereas the C11 peptide strongly binds hydroxyapatite. When C11 is modified on the surface groups of PAMAM, it anchors the entire molecule on demineralized dentin surfaces, thereby resisting washout and enhancing the mineralization efficiency, especially in the presence of collagenase in the cariogenic environment. PAMAM-C11 also inhibits matrix metalloproteinases in dentin and periodontal tissues, protecting the necessary mineralization templates and controlling periodontal destruction. Furthermore, PAMAM-C11 can promote the proliferation and osteogenic differentiation of periodontal ligament stem cells, indicating its potential use in periodontal regeneration. These findings were ultimately validated in an in vivo rat caries model. It can be concluded that PAMAM-C11 has great potential for clinical applications on root caries prevention.