State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
School of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
Small. 2022 Sep;18(38):e2203644. doi: 10.1002/smll.202203644. Epub 2022 Aug 21.
The integrity of collagen matrix structure is a prerequisite for effectively inducing biomimetic remineralization. Repeated low pH stimulation activates matrix metalloproteinases (MMPs) in dental caries. Activated MMPs cause the breakdown of collagen fibrils. Collagen stabilization is a major obstacle to the clinical application of remineralization templates. Here, galardin-loaded poly(amido amine) (PAMAM)-NGV (PAMAM-NGV@galardin, PNG) is constructed to induce collagen stabilization and dentin biomimetic remineralization simultaneously, in order to combat early caries in dentin. PAMAM acts in the role of nucleation template for dentin remineralization, while galardin acts as the role of MMPs inhibitor. NGV peptides modified on the surface of dendrimer core can form small clusters with synergistic movement in short range, and those short-range clusters can form domain areas with different properties on the surface of PAMAM core and restrict the movement of collagen, favoring collagen crosslinking, which can be explained through the computational simulation analysis results. NGV peptides and galardin show a dual collagen-protective effect, laying the foundation for the dentin remineralization effect induced by PAMAM. PNG induces dentin remineralization in an environment with collagenase, meanwhile showsing anti-dentin caries efficacy in vivo. These findings indicate that PNG has great potential to combat early dentin caries for future clinical application.
胶原基质结构的完整性是有效诱导仿生再矿化的前提条件。反复的低 pH 刺激会激活牙釉质龋中的基质金属蛋白酶（MMPs）。激活的 MMPs 会导致胶原原纤维的分解。胶原稳定是再矿化模板临床应用的主要障碍。在此，我们构建了载有加兰他敏的聚（酰胺-胺）（PAMAM-NGV@galardin，PNG），以同时诱导胶原稳定和牙本质仿生再矿化，从而对抗牙本质早期龋。PAMAM 作为牙本质再矿化的成核模板，而加兰他敏作为 MMPs 抑制剂。修饰在树突状核心表面的 NGV 肽可以在短程内协同运动形成小簇，这些短程簇可以在 PAMAM 核心表面形成具有不同性质的域区，并限制胶原的运动，有利于胶原交联，这可以通过计算模拟分析结果来解释。NGV 肽和加兰他敏对胶原具有双重保护作用，为 PAMAM 诱导的牙本质再矿化效果奠定了基础。PNG 在胶原酶存在的环境中诱导牙本质再矿化，同时在体内显示出抗牙本质龋的功效。这些发现表明，PNG 具有很大的潜力，可用于未来的临床应用来对抗早期牙本质龋。
