注射可能な吸収性ゲルのドラッグデリバリーシステムの開発－低侵襲の新規骨造成法

目的：为了达到理想的功能和美观要求，在种植前通常需要进行牙槽骨增高术。通常由复杂的侵入性手术组成的骨强化(尤其是垂直)仍然是具有挑战性的。本研究旨在探讨一种含有羟基磷灰石锶(SrHA)和藻酸盐(Alg)的可注射原位凝胶形成系统的可行性，并评价在SrHA-Alg系统中添加辛伐他汀(SIM)作为刺激剂以进一步以微创的方式促进骨形成的可行性。材料和方法：按照先前的方案，分别以低、中、高剂量的SIM制备SrHA-Alg-SIM溶液，每只动物接受200μ的单独骨膜下注射。分别于0、4、8周对新骨形成进行组织学和放射学评价。结果：海藻酸锶盐溶液材料注射后即可形成固体凝胶。因此，不需要缝合注射部位。在显微CT和组织切片观察中，低剂量组新生骨的数量均明显多于其他组。结论：大鼠颅骨骨膜下一次性注射SrHA-Alg-SIM溶液，无需任何干细胞或生长因子注射即可获得良好的成骨效果。低剂量的辛伐他汀对骨形成的促进作用似乎最好。该原位凝胶材料可能具有以微创方式进行局部骨强化的潜在治疗益处。

OBJECTIVES : To achieve ideal functional and aesthetic requirements, ridge augmentation is often required before dental implant placement. Bone augmentation (especially vertical), which normally consists of complex and invasive surgeries, still remains challenge. This study seeks to investigate the feasibility of an injectable in situ gel-forming system containing strontium hydroxyapatite (SrHA) and alginate (Alg) and also evaluate the addition of simvastatin (SIM) in the SrHA-Alg system as a stimulant to further enhance bone formation in the minimally invasive manner.MATERIAL AND METHODS : SrHA-Alg-SIM solution was prepared with low, medium and high doses of SIM according to the previous protocol, and each animal received a 200-μL single subperiosteal injection of either SrHA-Alg-SIM solution or SrHA-Alg solution alone as control. The new bone formation was assessed at 0, 4, and 8 weeks histologically and radiologically.RESULTS : The SrHA-alginate solution materials could form solid gel once injected. As such, no sutures were required to close the injection site. Significantly greater amount of new bone formation was observed in the SrHA-Alg-SIM (Low dose) group compared with the other groups both by micro-CT and by histological section.CONCLUSIONS : Rat calvarial bone augmentation was achieved by a single subperiosteal injection of SrHA-Alg-SIM solution without any administration of stem cells or growth factors. The low dose of simvastatin incorporated seemed to have the best stimulatory effect in bone formation. The in situ gel-forming material may hold potential therapeutic benefits for local bone augmentation in a minimally invasive manner.