双控TGF-β1－脂质体智能脱敏体系的合成及其在牙本质敏感中的研究

With the high incidence of dentin hypersensitivity, it has become a clinical problem to be solved. The conduction of pain was through the fluid inside the dentinal tubules, odontoblast and the surrounding nerve endings. If a new barrier could be formed between the dentinal tubules and pulp tissue, the stimulation from the fluid inside the dentinal tubules to the odontoblast could be blocked. TGF-β1 is a transforming growth factor, who can promote the formation of reparative dentin. But as a peptide substance, TGF-β1 would easily be inactivated in vivo, while liposome will act as an efficient carrier and compensate for the defect of TGF-β1. By sustaining effect of the opposite charge, liposome can smoothly get into the dentinal tubules and swim deeper, then the dentinal tubules will be blocked. Meanwhile, when the dentin surface was attacked by external acidity or thermal stimulation, the controlled release liposome will turn on the switch and release the TGF-β1 inside. Then TGF-β1 go through the full thickness of dentin and directly get in contact of the pulp tissue, promoting the formation of reparative dentin. Thus the barrier between the dentin and pulp tissue was formed and will relieve dentin hypersensitivity and appease pulp tissue.

牙本质敏感症的发生率不断攀升，已成为亟待解决的临床问题。其疼痛传导主体包括牙本质小管液、成牙本质细胞和其周围的神经末梢，若能在牙本质小管和牙髓组织间形成新的屏障，便能阻断牙本质小管液对成牙本质细胞的刺激。TGF-β1是一种转化生长因子，可促进修复性牙本质的形成。但作为一种多肽类物质，TGF-β1在体内外易失活，脂质体作为一种高效的药物载体，可弥补TGF-β1的这一缺陷。本项目将TGF-β1载入pH-温度双敏控释的脂质体，利用异种电荷相互吸引的效应引导载TGF-β1控释脂质体深入牙本质小管，通过pH-温度刺激控制TGF-β1释放，使其与牙髓组织中的成牙本质细胞直接接触，诱导成牙本质细胞的增殖和分化，促进修复性牙本质的形成，达到阻断牙本质敏感疼痛传导路径的目的，将对牙本质智能脱敏、自修复等领域的进步带来新突破。

牙本质敏感症的发生率不断攀升，已成为亟待解决的临床问题。其疼痛传导主体包括牙本质小管液、成牙本质细胞和其周围的神经末梢，若能在牙本质小管和牙髓组织间形成新的屏障 ，便能阻断牙本质小管液对成牙本质细胞的刺激。TGF-β1是一种转化生长因子，可促进修复性牙本质的形成。但作为一种多肽类物质，TGF-β在体内外易失活，脂质体作为一种高效的 药物载体，可弥补TGF-β1的这一缺陷。本项目研究内容为将TGF-β1载入pH-温度双敏控释的脂质体，利用异种电荷相互吸引的效应引导载TGF-β1控释脂质体深入牙本质小管，通过pH-温度刺激控制 TGF-β1释放，使其与牙髓组织中的成牙本质细胞直接接触，诱导成牙本质细胞的增殖和分化，促进修复性牙本质的形成，达到阻断牙本质敏感疼痛传导路径的目的。研究过程中，我们设计合成了具有pH和温度敏感性的控释脂质体，其粒径大小能够通过牙本质小管到达牙髓腔，并成功地装载了TGF-β1，通过pH和温度的刺激调控TGF-β1的释放，使TGF-β1能够作用于牙髓细胞和成牙本质细胞，进而促进修复性牙本质的形成，通过自修复方式形成新的内部屏障，达到通过生物矿化解决牙本质敏感的目的。这一新的治疗牙本质敏感的策略，从成牙本质细胞主动防御形成修复性牙本质屏障出发，可克服目前“被动沉积”治疗方法的不足，有望为牙本质敏感的智能脱敏提供新的参考和方向，并为牙本质缺损自修复材料的发展带来新的突破。