生物玻璃和殼聚糖改性的多孔活性骨水泥體內實驗研究_《中國修復重建外科雜志》

作者：

李陽 ¹ , 雷偉 ¹ , 王征 ² , 張毅 ¹ , 牛二龍 ¹ , 于龍 ¹ , 吳劍維 ¹ , 臧淵 ¹ , 劉峙辰 ¹ , 吳子祥 ¹

1第四軍醫大學西京醫院骨科（西安，710032）;;
2解放軍總醫院骨科;

關鍵詞：

多孔活性骨水泥聚甲基丙烯酸甲酯生物玻璃殼聚糖生物相容性生物力學兔

DOI：

10.7507/1002-1892.20130074

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目的探討新型多孔活性骨水泥（porous bioactive bone cement，PBC）在體內的生物力學特性，觀察材料降解及新骨形成情況。方法將聚甲基丙烯酸甲酯（polymethylmethacrylate，PMMA）粉末、生物玻璃粉末和殼聚糖顆粒按照不同質量百分比（W/W，%）比例配制成3種PBC：PBCⅠ（50︰40︰10）、PBCⅡ（40︰50︰10）和PBCⅢ（30︰60︰10）。32只10月齡新西蘭大白兔，雌雄不限，體重4.0～4.5 kg；制備直徑4 mm、深10 mm的雙側股骨髁部缺損模型。動物模型隨機分為4組（n=8），分別于雙側缺損處植入單純PMMA骨水泥（A組）、PBCⅠ（B組）、PBCⅡ（C組）和PBC Ⅲ（D組）。術后觀察實驗動物一般情況，1周時行膝關節正側位X線片檢查，3、6個月取標本行生物力學測試和Van-Gieson染色組織學觀察；取未植入的對應骨水泥行生物力學測試，作為對照。結果實驗動物均存活至實驗完成。1周X線片檢查示各組植入骨水泥位置良好。生物力學測試示，植入前及術后3、6個月，C、D組壓縮強度和彈性模量均較A組明顯下降（P lt; 0.05）；B組壓縮強度及3、6個月彈性模量較A組明顯下降（P lt; 0.05）；C、D組間差異無統計學意義（P gt; 0.05）。植入前及術后3個月，C、D組兩指標均較B組明顯下降（P lt; 0.05）；6個月，C組壓縮強度和D組彈性模量較B組明顯下降（P lt; 0.05）。與植入前相比，B、C、D組術后3、6個月兩指標均顯著下降（P lt; 0.05），A組無顯著變化（P gt; 0.05）。組織學觀察示，術后3個月，A組纖維結締組織環繞在PMMA和骨組織之間；B、C、D組殼聚糖顆粒有不同程度降解，其中D組降解最明顯；6個月，A組較前無明顯變化；B、C、D組可見骨組織沿殼聚糖降解后形成的空隙向骨水泥內部生長，C、D組骨生長優于B組。定量分析顯示，A、B、C、D組骨組織含量百分比呈逐漸上升趨勢，且各組內術后6個月顯著高于3個月。結論以PMMA粉末、生物玻璃粉末和殼聚糖顆粒按照質量百分比（W/W，%）40︰50︰10及30︰60︰10比例制備的PBC較單純PMMA骨水泥具有更好的生物相容性及生物力學特性。

引用本文： 李陽,雷偉,王征,張毅,牛二龍,于龍,吳劍維,臧淵,劉峙辰,吳子祥. 生物玻璃和殼聚糖改性的多孔活性骨水泥體內實驗研究. 中國修復重建外科雜志, 2013, 27(3): 320-325. doi: 10.7507/1002-1892.20130074 復制

1.	Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and earlyresults. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J, 2000, 9(5): 445-450.
2.	Obuchowski AM, Curcin A, Kostuik JP. Osteoporosis: Medical and Surgical Options//Mathis JM, Deramond H, Belkoff SM. Percutaneous Vertebroplasty. New York: Springer Verlag, 2002: 25-39.
3.	Lewis G. Injectable bone cements for use in vertebroplasty and kyphoplasty: state-of-the-art review. J Biomed Mater Res B Appl Biomater, 2006, 76(2): 456-468.
4.	Hernandez L, Munoz ME, Goni I, et al. New injectable and radiopaque antibiotic loaded acrylic bone cements. J Biomed Mater Res B Appl Biomater, 2008, 87(2): 312-320.
5.	Kurtz SM, Villarraga ML, Zhao K, et al. Static and fatigue mechanical behavior of bone cement with elevated barium sulfate content for treatment of vertebral compression fractures. Biomaterials, 2005, 26(17): 3699-3712.
6.	Grados F, Depriester C, Cayrolle G, et al. Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty. Rheumatology (Oxford), 2000, 39(12): 1410-1414.
7.	Trout AT, Kallmes DF, Kaufmann TJ. New fractures after vertebroplasty: adjacent fractures occur significantly sooner. AJNR Am J Neuroradiol, 2006, 27(1): 217-223.
8.	Ahn Y, Lee JH, Lee HY, et al. Predictive factors for subsequent vertebral fracture after percutaneous vertebroplasty. J Neurosurg Spine, 2008, 9(2): 129-136.
9.	Wasnich RD. Vertebral fracture epidemiology. Bone, 1996, 18(3 Suppl): 179S-183S.
10.	Baroud G, Nemes J, Heini P, et al. Load shift of the intervertebral disc after a vertebroplasty: a finite-element study. Eur Spine J, 2003, 12(4): 421-426.
11.	Nakano M, Hirano N, Matsuura K, et al. Percutaneous transpedicular vertebroplasty with calcium phosphate cement in the treatment of osteoporotic vertebral compression and burst fractures. J Neurosurg, 2002, 97(3 Suppl): 287-293.
12.	Thomas MV, Puleo DA. Calcium sulfate: Properties and clinical applications. J Biomed Mater Res B Appl Biomater, 2009, 88(2): 597-610.
13.	He Q, Chen H, Huang L, et al. Porous surface modified bioactive bone cement for enhanced bone bonding. PLoS One, 2012, 7(8): e42525.
14.	Berlemann U, Ferguson SJ, Nolte LP, et al. Adjacent vertebral failure after vertebroplasty: a biomechanical investigation. J Bone Joint Surg (Br), 2002, 84(5): 748-752.
15.	Orr TE, Villars PA, Mitchell SL, et al. Compressive properties of cancellous bone defects in a rabbit model treated with particles of natural bone mineral and synthetic hydroxyapatite. Biomaterials, 2001, 22(14): 1953-1959.
16.	Boger A, Bohner M, Heini P, et al. Properties of an injectable low modulus PMMA bone cement for osteoporotic bone. J Biomed Mater Res B Appl Biomater, 2008, 86(2): 474-482.
17.	Shi M, Kretlow JD, Spicer PP, et al. Antibiotic-releasing porous polymethylmethacrylate/gelatin/antibiotic constructs for craniofacial tissue engineering. J Control Release, 2011, 152(1): 196-205.
18.	López A, Hoess A, Thersleff T, et al. Low-modulus PMMA bone cement modified with castor oil. Biomed Mater Eng, 2011, 21(5-6): 323-332.
19.	Shinzato S, Nakamura T, Kokubo T, et al. PMMA-based bioactive cement: effect of glass bead filler content and histological change with time. J Biomed Mater Res, 2002, 59(2): 225-232.
20.	Hernández L, Parra J, Vázquez B, et al. Injectable acrylic bone cements for vertebroplasty based on a radiopaque hydroxyapatite. Bioactivity and biocompatibility. J Biomed Mater Res B Appl Biomater, 2009, 88(1): 103-114.
21.	Knabe C, Driessens FC, Planell JA, et al. Evaluation of calcium phosphates and experimental calcium phosphate bone cements using osteogenic cultures. J Biomed Mater Res, 2000, 52(3): 498-508.
22.	Shi Z, Neoh KG, Kang ET, et al. Antibacterial and mechanical properties of bone cement impregnated with chitosan nanoparticles. Biomaterials, 2006, 27(11): 2440-2449.
23.	Hench LL. The story of Bioglass. J Mater Sci Mater Med, 2006, 17(11): 967-978.
24.	Oonishi H, Hench LL, Wilson J, et al. Comparative bone growth behavior in granules of bioceramic materials of various sizes. J Biomed Mater Res, 1999, 44(1): 31-43.
25.	Jayabalan P, Tan AR, Rahaman MN, et al. Bioactive glass 13-93 as a subchondral substrate for tissue-engineered osteochondral constructs: a pilot study. Clin Orthop Relat Res, 2011, 469(10): 2754-2763.
26.	Ishihara K, Arai H, Nakabayashi N. Adhesive bone cement containing hydroxyapatite particle as bone compatible filler. J Biomed Mater Res, 1992, 26(8): 937-945.
27.	Barralet JE, Gaunt T, Wright AJ, et al. Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement. J Biomed Mater Res, 2002, 63(1): 1-9.
28.	Hench LL, Splinter RJ, Allen WC, et al. Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Mater Res Symp, 1971, 5(6): 117-141.

1. Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and earlyresults. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J, 2000, 9(5): 445-450.
2. Obuchowski AM, Curcin A, Kostuik JP. Osteoporosis: Medical and Surgical Options//Mathis JM, Deramond H, Belkoff SM. Percutaneous Vertebroplasty. New York: Springer Verlag, 2002: 25-39.
3. Lewis G. Injectable bone cements for use in vertebroplasty and kyphoplasty: state-of-the-art review. J Biomed Mater Res B Appl Biomater, 2006, 76(2): 456-468.
4. Hernandez L, Munoz ME, Goni I, et al. New injectable and radiopaque antibiotic loaded acrylic bone cements. J Biomed Mater Res B Appl Biomater, 2008, 87(2): 312-320.
5. Kurtz SM, Villarraga ML, Zhao K, et al. Static and fatigue mechanical behavior of bone cement with elevated barium sulfate content for treatment of vertebral compression fractures. Biomaterials, 2005, 26(17): 3699-3712.
6. Grados F, Depriester C, Cayrolle G, et al. Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty. Rheumatology (Oxford), 2000, 39(12): 1410-1414.
7. Trout AT, Kallmes DF, Kaufmann TJ. New fractures after vertebroplasty: adjacent fractures occur significantly sooner. AJNR Am J Neuroradiol, 2006, 27(1): 217-223.
8. Ahn Y, Lee JH, Lee HY, et al. Predictive factors for subsequent vertebral fracture after percutaneous vertebroplasty. J Neurosurg Spine, 2008, 9(2): 129-136.
9. Wasnich RD. Vertebral fracture epidemiology. Bone, 1996, 18(3 Suppl): 179S-183S.
10. Baroud G, Nemes J, Heini P, et al. Load shift of the intervertebral disc after a vertebroplasty: a finite-element study. Eur Spine J, 2003, 12(4): 421-426.
11. Nakano M, Hirano N, Matsuura K, et al. Percutaneous transpedicular vertebroplasty with calcium phosphate cement in the treatment of osteoporotic vertebral compression and burst fractures. J Neurosurg, 2002, 97(3 Suppl): 287-293.
12. Thomas MV, Puleo DA. Calcium sulfate: Properties and clinical applications. J Biomed Mater Res B Appl Biomater, 2009, 88(2): 597-610.
13. He Q, Chen H, Huang L, et al. Porous surface modified bioactive bone cement for enhanced bone bonding. PLoS One, 2012, 7(8): e42525.
14. Berlemann U, Ferguson SJ, Nolte LP, et al. Adjacent vertebral failure after vertebroplasty: a biomechanical investigation. J Bone Joint Surg (Br), 2002, 84(5): 748-752.
15. Orr TE, Villars PA, Mitchell SL, et al. Compressive properties of cancellous bone defects in a rabbit model treated with particles of natural bone mineral and synthetic hydroxyapatite. Biomaterials, 2001, 22(14): 1953-1959.
16. Boger A, Bohner M, Heini P, et al. Properties of an injectable low modulus PMMA bone cement for osteoporotic bone. J Biomed Mater Res B Appl Biomater, 2008, 86(2): 474-482.
17. Shi M, Kretlow JD, Spicer PP, et al. Antibiotic-releasing porous polymethylmethacrylate/gelatin/antibiotic constructs for craniofacial tissue engineering. J Control Release, 2011, 152(1): 196-205.
18. López A, Hoess A, Thersleff T, et al. Low-modulus PMMA bone cement modified with castor oil. Biomed Mater Eng, 2011, 21(5-6): 323-332.
19. Shinzato S, Nakamura T, Kokubo T, et al. PMMA-based bioactive cement: effect of glass bead filler content and histological change with time. J Biomed Mater Res, 2002, 59(2): 225-232.
20. Hernández L, Parra J, Vázquez B, et al. Injectable acrylic bone cements for vertebroplasty based on a radiopaque hydroxyapatite. Bioactivity and biocompatibility. J Biomed Mater Res B Appl Biomater, 2009, 88(1): 103-114.
21. Knabe C, Driessens FC, Planell JA, et al. Evaluation of calcium phosphates and experimental calcium phosphate bone cements using osteogenic cultures. J Biomed Mater Res, 2000, 52(3): 498-508.
22. Shi Z, Neoh KG, Kang ET, et al. Antibacterial and mechanical properties of bone cement impregnated with chitosan nanoparticles. Biomaterials, 2006, 27(11): 2440-2449.
23. Hench LL. The story of Bioglass. J Mater Sci Mater Med, 2006, 17(11): 967-978.
24. Oonishi H, Hench LL, Wilson J, et al. Comparative bone growth behavior in granules of bioceramic materials of various sizes. J Biomed Mater Res, 1999, 44(1): 31-43.
25. Jayabalan P, Tan AR, Rahaman MN, et al. Bioactive glass 13-93 as a subchondral substrate for tissue-engineered osteochondral constructs: a pilot study. Clin Orthop Relat Res, 2011, 469(10): 2754-2763.
26. Ishihara K, Arai H, Nakabayashi N. Adhesive bone cement containing hydroxyapatite particle as bone compatible filler. J Biomed Mater Res, 1992, 26(8): 937-945.
27. Barralet JE, Gaunt T, Wright AJ, et al. Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement. J Biomed Mater Res, 2002, 63(1): 1-9.
28. Hench LL, Splinter RJ, Allen WC, et al. Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Mater Res Symp, 1971, 5(6): 117-141.

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生物玻璃和殼聚糖改性的多孔活性骨水泥體內實驗研究

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《中國修復重建外科雜志》

生物玻璃和殼聚糖改性的多孔活性骨水泥體內實驗研究

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