Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United States.
The Bone Healing Research Laboratory, Department of Orthopedics and Rehabilitation, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States.
Mol Pharm. 2022 Dec 5;19(12):4654-4664. doi: 10.1021/acs.molpharmaceut.2c00644. Epub 2022 Nov 15.
Osteoarthritis (OA) can necessitate surgical interventions to restore the function of the joint in severe cases. Joint replacement surgery is one of the procedures implemented to replace the damaged joint with prosthetic implants in severe cases of OA. However, after successful implantation, a fraction of OA patients still require revision surgery due to aseptic prosthetic loosening. Insufficient osseointegration is one of the factors that contribute to such loosening of the bone implant, which is commonly made from titanium-based materials. Zoledronic acid (ZA), a potent bisphosphonate agent, has been previously shown to enhance osseointegration of titanium implants. Herein, we fabricated ZA/Ca composites using a reverse microemulsion method and coated them with 1,2-dioleoyl--glycero-3-phosphate monosodium salt (DOPA) to form ZA/Ca/DOPA composites. Titanium alloy screws were subsequently dip-coated with a suspension of the ZA/Ca/DOPA composites and poly(lactic--glycolic) acid (PLGA) in chloroform to yield Za/PLGA-coated screws. The coated screws exhibited a biphasic release profile with an initial burst release within 48 h, followed by a sustained release over 1 month. To assess their performance , the Za/PLGA screws were then implanted into the tibiae of Sprague-Dawley rats. After 8 weeks, microCT imaging showed new bone growth along the medullary cavity around the implant site, supporting the local release of ZA to enhance bone growth around the implant. Histological staining further confirmed the presence of new mineralized medullary bone growth resembling the cortical bone. Such local medullary growth represents an opportunity for future studies with alternative coating methods to fine-tune the local release of ZA from the coating and enhance complete osseointegration of the implant.
骨关节炎(OA)在严重情况下可能需要手术干预来恢复关节功能。关节置换手术是一种在严重 OA 情况下用假体植入物替代受损关节的程序之一。然而,在成功植入后,由于无菌性假体松动,仍有一部分 OA 患者需要进行翻修手术。骨植入物松动的一个原因是骨整合不足,这种植入物通常由钛基材料制成。唑来膦酸(ZA)是一种有效的双膦酸盐药物,先前已被证明可以增强钛植入物的骨整合。在此,我们使用反相微乳液法制备了 ZA/Ca 复合材料,并将其用 1,2-二油酰基-sn-甘油-3-磷酸单钠盐(DOPA)进行涂层,形成 ZA/Ca/DOPA 复合材料。随后,钛合金螺钉用 ZA/Ca/DOPA 复合材料和氯仿中的聚乳酸-羟基乙酸共聚物(PLGA)悬浮液进行浸涂,得到 Za/PLGA 涂层螺钉。涂层螺钉表现出双相释放曲线,在 48 小时内有初始突释,然后在 1 个月内持续释放。为了评估其性能,将 Za/PLGA 螺钉植入 Sprague-Dawley 大鼠的胫骨中。8 周后,微 CT 成像显示新骨沿着植入部位的髓腔生长,支持 ZA 的局部释放以增强植入物周围的骨生长。组织学染色进一步证实了新矿化髓腔骨生长的存在,类似于皮质骨。这种局部髓腔生长为未来的研究提供了机会,可以采用替代的涂层方法来微调涂层中 ZA 的局部释放,并增强植入物的完全骨整合。