Abstract：
To design and evaluate a matrix metalloproteinase 9 (MMP-9)-responsive hydrogel for vital pulp therapy.
A peptide linker with optimized sensitivity toward MMP-9 was crosslinked with 4-arm poly (ethylene glycol)-norbornene (PEG-NB) by thiol-norbornene photo-polymerization. This resulted in the formation of a hydrogel network in which the peptide IDR-1002 was incorporated. Hydrogel characterization and gelation kinetics were examined with Fourier-transform infrared spectroscopy, scanning electron microscopy, rheological testing, and swelling evaluation. Hydrogel degradation was examined through multiple exposure to pre-activated MMP-9, to simulate flare-ups of dental pulp inflammation. The IDR-1002 released from degraded hydrogels was measured with high-performance liquid chromatography. Effect of IDR-1002 released from hydrogels on one-week-old multispecies oral biofilms was evaluated using confocal laser scanning microscopy.
MMP-9-responsive, injectable, and photo-crosslinkable hydrogels were successfully synthesized. When hydrogel degradation and release of IDR-1002 were examined with exposure to pre-activated MMP-9, IDR-1002 release was significantly correlated with elevated levels of MMP-9 (p < 0.05). The effectiveness of IDR-1002 in killing bacteria in multispecies oral biofilms was significantly enhanced when the hydrogels were immersed in 10 nM or 20 nM pre-activated MMP-9, compared to immersion in phosphate-buffered saline (p < 0.05).
The MMP-9-responsive hydrogel is a promising candidate for on-demand delivery of bioactive agent in vital pulp therapy.
MMP-9 is one of the most important diagnostic and prognostic biomarkers for pulpitis. An MMP-9-responsive hydrogel has potential to be used as an in-situ on-demand release system for the diagnosis and treatment of dental pulp inflammation.
A peptide linker with optimized sensitivity toward MMP-9 was crosslinked with 4-arm poly (ethylene glycol)-norbornene (PEG-NB) by thiol-norbornene photo-polymerization. This resulted in the formation of a hydrogel network in which the peptide IDR-1002 was incorporated. Hydrogel characterization and gelation kinetics were examined with Fourier-transform infrared spectroscopy, scanning electron microscopy, rheological testing, and swelling evaluation. Hydrogel degradation was examined through multiple exposure to pre-activated MMP-9, to simulate flare-ups of dental pulp inflammation. The IDR-1002 released from degraded hydrogels was measured with high-performance liquid chromatography. Effect of IDR-1002 released from hydrogels on one-week-old multispecies oral biofilms was evaluated using confocal laser scanning microscopy.
MMP-9-responsive, injectable, and photo-crosslinkable hydrogels were successfully synthesized. When hydrogel degradation and release of IDR-1002 were examined with exposure to pre-activated MMP-9, IDR-1002 release was significantly correlated with elevated levels of MMP-9 (p < 0.05). The effectiveness of IDR-1002 in killing bacteria in multispecies oral biofilms was significantly enhanced when the hydrogels were immersed in 10 nM or 20 nM pre-activated MMP-9, compared to immersion in phosphate-buffered saline (p < 0.05).
The MMP-9-responsive hydrogel is a promising candidate for on-demand delivery of bioactive agent in vital pulp therapy.
MMP-9 is one of the most important diagnostic and prognostic biomarkers for pulpitis. An MMP-9-responsive hydrogel has potential to be used as an in-situ on-demand release system for the diagnosis and treatment of dental pulp inflammation.
摘要：
目的：设计并评估基质金属蛋白酶9（MMP-9）响应性水凝胶，用于重要牙髓治疗。
方法:通过巯基-降冰片烯光聚合将对MMP-9具有优化敏感性的肽接头与4臂聚(乙二醇)-降冰片烯(PEG-NB)交联。这导致其中掺入肽IDR-1002的水凝胶网络的形成。用傅里叶变换红外光谱研究了水凝胶的表征和凝胶动力学，扫描电子显微镜，流变测试，和肿胀评估。通过多次暴露于预活化的MMP-9来检查水凝胶降解，以模拟牙髓炎症的爆发。用高效液相色谱法测量从降解的水凝胶释放的IDR-1002。使用共聚焦激光扫描显微镜评估从水凝胶释放的IDR-1002对一周大的多物种口腔生物膜的影响。
结果：MMP-9反应，可注射,并成功合成了光交联水凝胶。当在暴露于预先活化的MMP-9的情况下检查IDR-1002的水凝胶降解和释放时,IDR-1002的释放与MMP-9水平的升高显著相关(p<0.05)。与浸入磷酸盐缓冲盐水相比,当水凝胶浸入10nM或20nM预活化的MMP-9中时,IDR-1002杀死多物种口腔生物膜的有效性显著增强(p<0.05)。
结论：MMP-9响应性水凝胶是重要牙髓治疗中按需递送生物活性剂的有希望的候选者。
结论：MMP-9是牙髓炎最重要的诊断和预后生物标志物之一。MMP-9响应性水凝胶具有用作诊断和治疗牙髓炎症的原位按需释放系统的潜力。
方法:通过巯基-降冰片烯光聚合将对MMP-9具有优化敏感性的肽接头与4臂聚(乙二醇)-降冰片烯(PEG-NB)交联。这导致其中掺入肽IDR-1002的水凝胶网络的形成。用傅里叶变换红外光谱研究了水凝胶的表征和凝胶动力学，扫描电子显微镜，流变测试，和肿胀评估。通过多次暴露于预活化的MMP-9来检查水凝胶降解，以模拟牙髓炎症的爆发。用高效液相色谱法测量从降解的水凝胶释放的IDR-1002。使用共聚焦激光扫描显微镜评估从水凝胶释放的IDR-1002对一周大的多物种口腔生物膜的影响。
结果：MMP-9反应，可注射,并成功合成了光交联水凝胶。当在暴露于预先活化的MMP-9的情况下检查IDR-1002的水凝胶降解和释放时,IDR-1002的释放与MMP-9水平的升高显著相关(p<0.05)。与浸入磷酸盐缓冲盐水相比,当水凝胶浸入10nM或20nM预活化的MMP-9中时,IDR-1002杀死多物种口腔生物膜的有效性显著增强(p<0.05)。
结论：MMP-9响应性水凝胶是重要牙髓治疗中按需递送生物活性剂的有希望的候选者。
结论：MMP-9是牙髓炎最重要的诊断和预后生物标志物之一。MMP-9响应性水凝胶具有用作诊断和治疗牙髓炎症的原位按需释放系统的潜力。
