Antitumor effect of 5-fluorouracil microsphere composite on bone defect repairs

doi:10.3969/j.issn.2095-4344.2013.12.006

Abstract

Abstract:

BACKGROUND: Previous studies have successfully prepared nano-hydroxyapatite-poly(3-hydroxybutyrate- hydroxyvalerate)/polyethylene glycol-5-fluorouracil.
OBJECTIVE: To discuss the effect of nano-hydroxyapatite-poly(3-hydroxybutyrate-hydroxyvalerate)/polyethylene glycol-5-fluorouracil composite on bone defect repair and against bone tumor.
METHODS: Bone tumor models were induced by injection of VX2 carcinoma cell suspension into the medullary cavity of right tibias in 72 New Zealand white rabbits through the knee joints. Partial resection of the tibia was performed to form bone defects that were adjacent to bone tumors. After modeling, all the rabbits were randomized into experimental and control groups. Nano-hydroxyapatite-poly(3-hydroxybutyrate-hydroxyvalerate)/ polyethylene glycol-5-fluorouracil and nano-hydroxyapatite-poly(3-hydroxybutyrate-hydroxyvalerate)/ polyethylene glycol artificial bone were implanted into bone defects, respectively, in the experimental and control groups.
RESULTS AND CONCLUSION: (1) Inorganic content was decreased gradually in the two groups, especially in the experimental group. (2) X-ray examination: At 24 weeks after implantation, the implant became smaller than that in the early stage after implantation. However, there were no changes in the implant volume in the control group, and tumor volume in the control group was enlarged progressively. (3) Biomechanical detection: At 24 weeks after implantation, the maximal torque of the lower limbs in the experimental group was significantly higher than that in the control group (P < 0.01). (4) Bone mineral density in the two groups was firstly decreased and then increased at 2-24 weeks after implantation. The changes in the bone mineral density of the experimental group were significant. (6) Tumor volume was decreased in the experimental group and increased in the control group at 24 weeks after implantation. These findings indicate that nano-hydroxyapatite-poly(3-hydroxybutyrate- hydroxyvalerate)/polyethylene glycol-5-fluorouracil can perfectly repair bone defects and exert a remarkable effect against tumor growth.

Key words: biomaterials, nanobiomaterials, nano-hydroxyapatite, poly(3-hydroxybutyrate-hydroxyvalerate)/ polyethylene glycol, 5-fluorouracil, bone tumors, bone defects, inorganic, biomechanics, bone density, biomaterial photographs-containing paper

CLC Number:

R318

Feng Wei, Jin An-min, Liu Ji-en, Gou Rui-en, Guan Chun-hui, Liang Qi-feng, Xin Ruo-bing. Antitumor effect of 5-fluorouracil microsphere composite on bone defect repairs[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(12): 2131-2137.

Figures/Tables 7

2.1 实验动物大体观察结果整个实验过程中，有3只动物死亡，其中实验组2只，对照组1只，1只为麻醉过深术后立即死亡，另2只分别系术后第39，45天时突然死亡，死因不明。与实验因素无关，均予以剔除并及时补充。大部分动物术肢在术后第1天即出现不同程度的肿胀，3-5 d后消失，伤口愈合良好，均于10 d拆线。术后2 d内活动减少，食欲降低，毛色灰暗，其后活动、进食情况逐渐恢复至基本正常，精神状态也随之好转。 2.2 术后不同时间点实验组与对照组植入物大体观察结果取材后可见对照组术后2，4周材料与骨界面清晰，无明显成骨，上下端瘤体向两侧浸润；6-16周较多软组织覆盖植入材料，可见少量新骨形成，两端肿瘤进一步向远侧和近侧生长。实验组术后4周同对照组，瘤体进行性向两端侵袭；6周在植入材料与宿主骨之间可见到软骨组织，肿瘤侵袭的范围无明显增加；16周时材料与骨交界处有外骨痂出现，大体观察见肿瘤体积减小；24周时新骨明显增多，材料体积变小，骨缺损得到初步修复，肿瘤体积进一步减小，但仍有部分残存。标本固定后从正中剖开，塑料包埋，观察材料降解情况。两组材料在术后4周时材料体积与植入时基本相同，无明显降解迹象。至16周时，材料体积略变小，两端由部分新生骨痴替代，中间无新骨形成，材料外缘不规则，有大量小颗粒，新骨钙化程度较高，部分可见新骨连接，24周时新骨形成量进一步增加，骨断端骨性连接，骨缺损得到初步修复，但仍有部分植入材料残留，不能分辨出新骨与材料之间的边界，尚未见到髓腔再通。 2.3 实验组与对照组胫骨标本无机质含量测定两组无机质含量随着时间的延长均有不同程度降低，无机成分均迅速减少，表1，图2，尤以实验组明显。"

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