含聚乳酸-羥基乙酸共聚物的新型磷酸鈣骨水泥體內降解性能研究_《中國修復重建外科雜志》

作者：

廖紅興 ^1,2 , 段昕 ¹ , 張紫機 ¹ , 鄒華章 ³ , 葉建東 ⁴ , 廖威明 ¹

1中山大學附屬第一醫院骨科-顯微外科醫學部（廣州，510080）;;
2 梅州市人民醫院骨科;;
3 廣州醫學院第四附屬醫院骨科;;
4 華南理工大學生物材料研究所;

關鍵詞：

磷酸鈣骨水泥聚乳酸-羥基乙酸共聚物體內降解兔

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目的探討含聚乳酸-羥基乙酸共聚物（poly lactic-co-glycolic acid，PLGA）的新型磷酸鈣骨水泥（calcium phosphate cement，CPC）（CPC/PLGA）體內降解性能，為臨床試驗奠定基礎。方法按照45%磷酸氫鈣、45%部分結晶磷酸鈣、10% PLGA比例，制備CPC/PLGA。健康成年新西蘭兔32只，體重2.2～3.0 kg，雌雄各半；隨機分為CPC/PLGA組（實驗組，n=17）及CPC組（對照組，n=15）。兩組實驗動物制備雙側股骨內側髁直徑4.5 mm、深1.5 cm骨缺損模型，右側骨缺損分別采用CPC/PLGA及CPC修復，左側不作處理作為空白對照。術后觀察實驗動物一般情況，術后2、4、8、16、24周兩組取材行組織學觀察、骨形態計量學分析，術后8周及16周實驗組取材行掃描電鏡觀察。結果實驗動物均存活至實驗結束。組織學觀察顯示，隨時間延長，實驗組CPC/PLGA逐漸降解，并有新生骨小梁從邊緣長入其中，并且增粗、增長，24周時材料基本降解，被新生骨小梁取代；對照組CPC降解明顯較實驗組延遲。實驗組術后總骨組織含量百分比為44.9% ± 23.7%，顯著高于對照組的25.7% ± 10.9%（t=3.302，P=0.001）；實驗組術后4周骨組織含量百分比與對照組比較，差異無統計學意義（P gt; 0.05），8、16、24周均顯著高于對照組，差異有統計學意義（P lt; 0.05）。掃描電鏡觀察結果顯示，實驗組術后8周CPC/PLGA降解后形成孔徑為100～300 μm孔隙；隨著時間延長，16周時新生骨小梁長入孔隙內，并與殘余骨水泥牢固結合。結論CPC/PLGA植入兔體內后具有良好的降解性能，有望成為一種良好骨移植材料。

引用本文： 廖紅興,段昕,張紫機,鄒華章,葉建東,廖威明. 含聚乳酸-羥基乙酸共聚物的新型磷酸鈣骨水泥體內降解性能研究. 中國修復重建外科雜志, 2012, 26(8): 934-938. doi: 復制

1.	Hench LL, Wilson J. An introduction to bioceramics. New Jersey: World Scientific Publishing Co Pte Ltd, 1993: 1-24.
2.	Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials, 1999, 20(23-24): 2287-2303.
3.	Xu HH, Burgueral EF, Carey LE. Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures. Biomaterials, 2007, 28(26): 3786-3796.
4.	Kruyt MC, Persson C, Johansson G, et al. Towards injectable cell-based tissue-engineered bone: the effect of different calcium phosphate microparticles and pre-culturing. Tissue Eng, 2006, 12(2): 309-317.
5.	Van Lieshout EM, Van Kralingen GH, El-Massoudi Y, et al. Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery. BMC Musculoskelet Disord, 2011, 12: 34.
6.	Wang X, Ye J, Wang Y, et al. Hydration mechanism of a novel PCCP + DCPA cement system. J Mater Sci Mater Med, 2008, 19(2): 813-816.
7.	Qi X, Ye J, Wang Y. Improved injectability and in vitro degradation of a calcium phosphate cement containing poly (lactide-co-glycolide)microspheres. Acta Biomater, 2008, 4(6): 1837-1845.
8.	Hollinger JO, Kleinechmidt JC. The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg, 1990, 1(1): 60-68.
9.	Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res, 1986, (205): 299-308.
10.	Fernández E, Vald MD, Gel MM, et al. Modulation of porosity in apatitic cements by the use of alpha-tricalcium phosphate-calcium sulphate dihydrate mixtures. Biomaterials, 2005, 26(17): 3395-3404.
11.	Fernández E, Sarda S, Hamcerencu M, et al. High-strength apatitic cement by modification with superplasticizers. Biomaterials, 2005, 26(15): 2289-2296.
12.	Manjubala I, Sivakumar M, Sureshkumar RV, et al. Bioactive and osseointegration study of calcium phosphate ceramic of different chemical composition. J Biomed Mater Res, 2002, 63(2): 200-208.
13.	Apelt D, Theiss F, El-Warrak AO, et al. In vivo behavior of three different injectable hydraulic calcium phosphate cements. Biomaterials, 2004, 25(7-8): 1439-1451.
14.	BohnerM, Theiss F, Apelt D, et al. Compositional changes of adicalcium phosphate dihydrate cement after implantation in sheep. Biomaterials, 2003, 24(20): 3463-3474.
15.	Ruhé PQ, Hedberg EL, Padron NT, et al. Biocompatibility and degradation of poly (DL-lactic-co-glycolic acid)/calcium phosphate cement composites. J Biomed Mater Res A, 2005, 74(4): 533-544.
16.	Simon CG Jr, Khatri CA, Wight SA, et al. Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly (lactide-co-glycolide)microspheres. J Orthop Res, 2002, 20(3): 473-482.
17.	鄒華章, 廖威明, 段昕, 等. 新型可注射磷酸鈣骨水泥在椎體后凸成形術中的生物力學評價. 中華生物醫學工程雜志, 2011, 17(2): 151-155.
18.	Flautre B, Delecourt C, Blary MC, et al. Volume effect on biological properties of a calcium phosphate hydraulic cement: Experimental study in sheep. Bone, 1999, 25(2 Suppl): 35s-39s.
19.	李朵, 魏啟幼, 范松青, 等. 不脫鈣骨組織包埋技術的改進. 臨床與實驗病理學雜志, 2005, 21(6): 731-733.
20.	LeGeros RZ, Lin S, Rohanizadeh R, et al. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Mater Sci Mater Med, 2003, 14(3): 201-209.
21.	Flautre B, Descamps M, Delecourt C, et al. Pores HA ceramic for bone replacement: role of the pores and interconnections—experimental study in rabbit. J Mater Sci Mater Med, 2001, 12(8): 679-682.

1. Hench LL, Wilson J. An introduction to bioceramics. New Jersey: World Scientific Publishing Co Pte Ltd, 1993: 1-24.
2. Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials, 1999, 20(23-24): 2287-2303.
3. Xu HH, Burgueral EF, Carey LE. Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures. Biomaterials, 2007, 28(26): 3786-3796.
4. Kruyt MC, Persson C, Johansson G, et al. Towards injectable cell-based tissue-engineered bone: the effect of different calcium phosphate microparticles and pre-culturing. Tissue Eng, 2006, 12(2): 309-317.
5. Van Lieshout EM, Van Kralingen GH, El-Massoudi Y, et al. Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery. BMC Musculoskelet Disord, 2011, 12: 34.
6. Wang X, Ye J, Wang Y, et al. Hydration mechanism of a novel PCCP + DCPA cement system. J Mater Sci Mater Med, 2008, 19(2): 813-816.
7. Qi X, Ye J, Wang Y. Improved injectability and in vitro degradation of a calcium phosphate cement containing poly (lactide-co-glycolide)microspheres. Acta Biomater, 2008, 4(6): 1837-1845.
8. Hollinger JO, Kleinechmidt JC. The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg, 1990, 1(1): 60-68.
9. Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res, 1986, (205): 299-308.
10. Fernández E, Vald MD, Gel MM, et al. Modulation of porosity in apatitic cements by the use of alpha-tricalcium phosphate-calcium sulphate dihydrate mixtures. Biomaterials, 2005, 26(17): 3395-3404.
11. Fernández E, Sarda S, Hamcerencu M, et al. High-strength apatitic cement by modification with superplasticizers. Biomaterials, 2005, 26(15): 2289-2296.
12. Manjubala I, Sivakumar M, Sureshkumar RV, et al. Bioactive and osseointegration study of calcium phosphate ceramic of different chemical composition. J Biomed Mater Res, 2002, 63(2): 200-208.
13. Apelt D, Theiss F, El-Warrak AO, et al. In vivo behavior of three different injectable hydraulic calcium phosphate cements. Biomaterials, 2004, 25(7-8): 1439-1451.
14. BohnerM, Theiss F, Apelt D, et al. Compositional changes of adicalcium phosphate dihydrate cement after implantation in sheep. Biomaterials, 2003, 24(20): 3463-3474.
15. Ruhé PQ, Hedberg EL, Padron NT, et al. Biocompatibility and degradation of poly (DL-lactic-co-glycolic acid)/calcium phosphate cement composites. J Biomed Mater Res A, 2005, 74(4): 533-544.
16. Simon CG Jr, Khatri CA, Wight SA, et al. Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly (lactide-co-glycolide)microspheres. J Orthop Res, 2002, 20(3): 473-482.
17. 鄒華章, 廖威明, 段昕, 等. 新型可注射磷酸鈣骨水泥在椎體后凸成形術中的生物力學評價. 中華生物醫學工程雜志, 2011, 17(2): 151-155.
18. Flautre B, Delecourt C, Blary MC, et al. Volume effect on biological properties of a calcium phosphate hydraulic cement: Experimental study in sheep. Bone, 1999, 25(2 Suppl): 35s-39s.
19. 李朵, 魏啟幼, 范松青, 等. 不脫鈣骨組織包埋技術的改進. 臨床與實驗病理學雜志, 2005, 21(6): 731-733.
20. LeGeros RZ, Lin S, Rohanizadeh R, et al. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Mater Sci Mater Med, 2003, 14(3): 201-209.
21. Flautre B, Descamps M, Delecourt C, et al. Pores HA ceramic for bone replacement: role of the pores and interconnections—experimental study in rabbit. J Mater Sci Mater Med, 2001, 12(8): 679-682.

《中國修復重建外科雜志》

含聚乳酸-羥基乙酸共聚物的新型磷酸鈣骨水泥體內降解性能研究

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《中國修復重建外科雜志》

含聚乳酸-羥基乙酸共聚物的新型磷酸鈣骨水泥體內降解性能研究

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