Gingipain-Responsive Thermosensitive Hydrogel Loaded with SDF-1 Facilitates In Situ Periodontal Tissue Regeneration
Gingipain-Responsive Thermosensitive Hydrogel Loaded with SDF-1 Facilitates In Situ Periodontal Tissue Regeneration
复制标题
负载SDF-1的牙龈蛋白酶响应性热敏水凝胶促进原位牙周组织再生
DOI：
10.1021/acsami.1c08855
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发表时间：
2021-07-29
影响因子：
9.5
通讯作者：
Ge, Shaohua
中科院分区：
文献类型：
--
作者：
Liu, Shiyue;Wang, Ya-Nan;Ge, Shaohua
现有牙周炎局部给药系统存在抗菌效果差、牙周再生不理想等问题。在这项研究中，合成了一种智能牙痛反应水凝胶(PEGPD@SDF-1)，作为一种环境敏感的按需给药载体。以聚乙二醇二丙烯酸酯(PEGDA)为支架，以二硫苏糖醇(DTT)为载体，通过Michael-type加成反应合成了PEGPD@SDF-1水凝胶，并进一步负载了基质细胞衍生因子-1(SDF-1)。具有锚定多肽-短抗菌肽(SAMP)锚定结构的FPM可被牙龈痛特异性切割，SAMP从水凝胶中释放出来，对牙龈痛产生抗菌作用。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、降解评价以及SAMP和SDF-1的释放曲线描述等手段对水凝胶的性能进行了表征。体外实验结果表明，PEGPD@SDF-1水凝胶具有良好的生物相容性，能促进牙周膜干细胞的增殖、迁移和成骨分化。抗菌试验表明，PEGPD@SDF-1水凝胶可在牙周疼痛刺激下释放SAMP，从而强烈抑制牙龈卟啉单胞菌的生长。此外，体内研究表明，PEGPD@SDF-1水凝胶抑制牙龈假单胞菌的繁殖，创造低炎症环境，促进CD90+/CD34-基质细胞的募集，并诱导成骨。综上所述，这些结果表明，牙周疼痛响应性PEGPD@SDF-1水凝胶可以促进牙周组织的原位再生，是牙周炎局部按需给药系统的一种有前途的候选药物。
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 in vitro 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 Porphyromonas gingivalis. Furthermore, the study in vivo indicated that the PEGPD@SDF-1 hydrogel inhibited P. gingivalis 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 in situ periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.