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局部给予阿司匹林与β-磷酸三钙/聚乳酸-羟基乙酸共聚物(β-TCP/PLGA)可增强骨质疏松性骨再生。

Local administration of aspirin with β-tricalcium phosphate/poly-lactic-co-glycolic acid (β-TCP/PLGA) could enhance osteoporotic bone regeneration.

机构信息

Department of Trauma Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe shan Xi Road, Wuhu, 241001, Anhui, People's Republic of China.

Department of Geriatrics, The Second Affiliated Hospital of Wannan Medical College, No. 123, Kangfu Road, Wuhu, 241000, Anhui, People's Republic of China.

出版信息

J Bone Miner Metab. 2019 Nov;37(6):1026-1035. doi: 10.1007/s00774-019-01008-w. Epub 2019 May 10.

DOI:10.1007/s00774-019-01008-w
PMID:31076895
Abstract

Composite materials β-tricalcium phosphate (β-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into β-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified β-TCP (TP) was prepared by mixing sieved granules of β-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and β-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/β-TCP/ASP occured in a dose-dependent manner.

摘要

复合材料β-磷酸三钙 (β-TCP) 和聚乳酸-共-羟基乙酸 (PLGA) 在以前的研究中已实现了无需细胞移植的稳定骨再生。最近的研究表明,阿司匹林 (ASP) 在促进骨再生方面具有巨大潜力。本研究的目的是将 PLGA 掺入β-TCP 中,同时局部给予低剂量的单次 ASP 给药,以增强其体内生物降解和骨组织生长。在创建啮齿动物临界大小股骨干骺端骨缺损后,通过混合筛过的β-TCP 和 PLGA(50:50,v/v)颗粒来制备 PLGA 改性的β-TCP(TP),用于医疗用途,然后将含有滴注 50µg/0.1ml 和 100µg/0.1ml 阿司匹林溶液的 TP 植入到去卵巢大鼠的缺损部位,直到 8 周后死亡。采集大鼠远端股骨缺损区进行组织学、微 CT、生物力学和实时 RT-PCR 评估。我们的研究结果表明,单次局部给予 ASP 联合局部使用 TP 可以增加去卵巢大鼠缺损的愈合。单次局部给予阿司匹林可以增加参与调节骨形成和血管生成的基因在缺损区域的转录,并抑制破骨细胞活性。此外,较高剂量的单次局部给予 ASP 和 TP 的治疗方法对加速局部骨形成的作用强于使用较低剂量的 ASP。我们的研究结果表明,单次局部给予 ASP 和β-TCP/PLGA 的组合对骨质疏松症大鼠局部骨形成具有相加作用,PLGA/β-TCP/ASP 的骨再生呈剂量依赖性。

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