Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, China.
Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, China.
ACS Appl Mater Interfaces. 2021 Aug 11;13(31):36880-36893. doi: 10.1021/acsami.1c08855. Epub 2021 Jul 29.
Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide-short antimicrobial peptide (SAMP)-anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results indicated the PEGPD@SDF-1 hydrogel exhibited preferable biocompatibility and could promote the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Antibacterial testing demonstrated that the PEGPD@SDF-1 hydrogel released the SAMP stressfully in response to gingipain stimulation, thereby strongly inhibiting the growth of . Furthermore, the study indicated that the PEGPD@SDF-1 hydrogel inhibited reproduction, created a low-inflammatory environment, facilitated the recruitment of CD90+/CD34- stromal cells, and induced osteogenesis. Taken together, these results suggest that the gingipain-responsive PEGPD@SDF-1 hydrogel could facilitate periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.
现有的牙周炎局部药物递送系统存在抗菌效果差和牙周组织再生不满意等问题。在本研究中，设计了一种智能的牙龈蛋白酶响应水凝胶（PEGPD@SDF-1）作为一种环境敏感的载体用于按需药物递送。PEGPD@SDF-1 水凝胶是由聚乙二醇二丙烯酸酯（PEG-DA）基支架、二硫苏糖醇（DTT）和一种新型设计的功能肽模块（FPM）通过迈克尔加成反应合成的，水凝胶进一步负载了基质细胞衍生因子-1（SDF-1）。FPM 具有锚肽-短抗菌肽（SAMP）-锚肽的结构，可以被牙龈蛋白酶特异性切割，并且 SAMP 从水凝胶中释放出来，以响应牙龈蛋白酶发挥抗菌作用。通过扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、溶胀比分析、降解评价和 SAMP 和 SDF-1 的释放曲线描述对水凝胶性质进行了表征。结果表明，PEGPD@SDF-1 水凝胶具有较好的生物相容性，可以促进牙周膜干细胞（PDLSCs）的增殖、迁移和成骨分化。抗菌试验表明，PEGPD@SDF-1 水凝胶在响应牙龈蛋白酶刺激时会强烈释放 SAMP，从而强烈抑制 的生长。此外，研究表明，PEGPD@SDF-1 水凝胶抑制 繁殖，创造低炎症环境，有利于 CD90+/CD34-基质细胞的募集，并诱导成骨。综上所述，这些结果表明，牙龈蛋白酶响应的 PEGPD@SDF-1 水凝胶可以促进牙周组织再生，是一种有前途的牙周炎按需局部药物递送系统的候选物。
