浓缩生长因子负载脂肪干细胞预防SD大鼠双膦酸盐类药物相关性颌骨骨坏死

Adipose-derived stem cells integrated with concentrated growth factors prevent bisphosphonaterelated osteonecrosis of the jaws in SD rats

背景:双膦酸盐类药物相关性颌骨骨坏死的病因可能涉及侵袭性牙科手术、感染、颌骨机械性损伤、免疫抑制剂和化疗药物等,但其潜在机制和治疗尚不清楚,预防是主要的临床命题。目的:探讨浓缩生长因子负载脂肪干细胞对双膦酸盐类药物相关性颌骨骨坏死的全面预防作用。方法:40只SD大鼠随机分为4组:对照组、唑来膦酸组、浓缩生长因子组、脂肪干细胞联合浓缩生长因子组,每组10只。除对照组外,其他3组尾静脉注射唑来膦酸(80μg/kg),每周1次,连续给药12周建立双膦酸盐类药物相关性颌骨骨坏死模型;对照组尾静脉注射生理盐水0.1 mL。以上4组均于第8周时拔除右侧下颌第一磨牙,浓缩生长因子组拔牙后于拔牙窝立即植入0.5 cm×0.5 cm浓缩生长因子;脂肪干细胞联合浓缩生长因子组拔牙后于拔牙窝立即植入0.5 cm×0.5 cm浓缩生长因子/脂肪干细胞复合物,对照组和唑来膦酸组拔牙后不处理;拔牙后8周过量麻醉处死大鼠,分别通过拔牙创观察、Micro-CT、苏木精-伊红染色评估牙龈再生、拔牙创周围骨组织再生情况。结果与结论:相对于其他3组,浓缩生长因子/脂肪干细胞复合物明显促进了拔牙创周围软组织愈合和新骨形成,减少了死骨形成量,有效预防了双膦酸盐类药物相关性颌骨骨坏死的发生。

BACKGROUND:Bisphosphonate-related osteonecrosis of jaw may involve invasive dental surgery,infection,jaw injury,immunosuppressive agents and chemotherapeutic drugs,and its potential mechanism and treatment are not clear.Prevention is the main clinical proposition.OBJECTIVE:To explore the preventive effect of concentrated growth factors integrated with adipose-derived stem cells on bisphosphonate-related osteonecrosis of jaw.METHODS:Forty Sprague-Dawley rats were randomly assigned to four groups:control group,zoledronic acid group,concentrated growth factor group,and adipose-derived stem cells combined with concentrated growth factor group(n=10 per group).Except the control group,rats in the other three groups were injected with zoledronic acid(80μg/kg)through the tail vein once a week for 12 consecutive weeks to establish a bisphosphonate-related osteonecrosis of jaw model.Rats in the control group were injected with 0.1 mL of saline through the tail vein.The right mandibular first molar was extracted at the 8th week.In the concentrated growth factor group,0.5 cm×0.5 cm concentrated growth factors were implanted immediately after tooth extraction.In the adipose-derived stem cells combined with concentrated growth factor group,0.5 cm×0.5 cm concentrated growth factor/adipose-derived stem cell complex was implanted into the extraction socket immediately after tooth extraction.The control group and zoledronic acid group were not treated after tooth extraction.The rats were killed 8 weeks after extraction.The gingival regeneration and bone tissue regeneration around the extraction wound were detected by observation of tooth extraction wound,Micro-CT and hematoxylin-eosin staining.RESULTS AND CONCLUSION:Compared with other three groups,concentrated growth factor/adipose-derived stem cell complex significantly promoted the healing of soft tissue and new bone formation around tooth extraction,reduced the dead bone formation,and effectively prevented the occurrence of bisphosphonate-related osteonecrosis of jaw.