萬古霉素陽離子脂質體復合納米羥基磷灰石/ 殼聚糖/魔芋葡甘聚糖治療兔慢性感染性骨缺損_《中國修復重建外科雜志》

作者：

黃金亮 , 馬濤 , 唐輝 , 范新宇 , 徐永清

成都軍區昆明總醫院全軍骨科中心（昆明，650032）;

關鍵詞：

納米羥基磷灰石/ 殼聚糖/ 魔芋葡甘聚糖支架，陽離子脂質體，萬古霉素，感染性骨缺損，兔

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【摘要】目的檢驗陽離子脂質體包封萬古霉素復合納米羥基磷灰石/ 殼聚糖/ 魔芋葡甘聚糖（nanohydroxyapatite/
chitosan/konjac glucomannan，n-HA/CS/KGM）支架體內抗感染及骨修復活性。方法取6 月齡健康新
西蘭大白兔51 只，體重1.5 ～ 3.0 kg，用金黃色葡萄球菌制備慢性感染性雙側脛骨骨缺損模型。將造模后4 周存活的48
只兔隨機分為4 組，每組12 只。根據以下分組方法，分別于雙側骨缺損處植入相應支架。A 組：清創后不作任何處理；B
組：n-HA/CS/KGM 空白支架組；C 組：萬古霉素復合n-HA/CS/KGM 支架組；D 組：萬古霉素陽離子脂質體復合n-HA/
CS/KGM 支架組。治療后8 周行大體、骨缺損修復、組織學觀察以及X 線片、細菌學檢查。結果實驗動物造模后4 周
X 線片顯示明顯骨質缺損、低密度影及軟組織腫脹影，Norden 評分均 gt; 3 分，為（3.83 ± 0.52）分。治療后8 周大體觀察：C、D 組竇道已愈合，A、B 組仍有竇道；大體觀察病理評分C、D 組明顯優于A、B 組（P lt; 0.05）。骨缺損修復觀察：D 組骨缺損已修復，骨缺損最長徑顯著優于A、B、C 組（P lt; 0.05）。X 線片檢查：C、D 組可見新骨形成，A、B 組可見骨膜反應及髓腔低密度影；Norden 評分D 組明顯小于A、B、C 組（P lt; 0.05）。組織學觀察：HE 染色示C、D 組可見大量骨小梁形成，
纖維增生，未見明顯感染跡象，A、B 組仍可見中性粒細胞積聚；Smeltzer 評分C、D 組明顯優于A、B 組（P lt; 0.05）。細菌
學檢查：C、D 組陰性率明顯高于A、B 組（P lt; 0.05）。結論萬古霉素陽離子脂質體復合n-HA/CS/KGM 支架可很好治
療兔慢性感染性脛骨骨缺損，為臨床上治療慢性感染性骨缺損提供了新思路。

引用本文： 黃金亮,馬濤,唐輝,范新宇,徐永清. 萬古霉素陽離子脂質體復合納米羥基磷灰石/ 殼聚糖/魔芋葡甘聚糖治療兔慢性感染性骨缺損. 中國修復重建外科雜志, 2012, 26(2): 190-195. doi: 復制

1.	Gustilo RB, Merkow RL, Templeman D. The management of open fractures. J Bone Joint Surg (Am), 1990, 72(2): 299-304.
2.	de Carvalho CC. Biofilms: recent developments on an old battle. Recent Pat Biotechnol, 2007, 1(1): 49-57.
3.	Widmer AF. New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis, 2001, 33 Suppl 2: S94-106.
4.	Kim HJ, Jones MN. The delivery of benzyl penicillin to Staphylococcus aureus biofilms by use of liposomes. J Liposome Res, 2004, 14(3-4): 123-139.
5.	Ma T, Shang BC, Tang H, et al. Nano-hydroxyapatite/chitosan/konjac glucomannan scaffolds loaded with cationic liposomal vancomycin: preparation, in vitro release and activity against Staphylococcus aureus biofilms. J Biomater Sci Polym Ed, 2011, 22(12): 1669-1681.
6.	Norden CW, Myerowitz RL, Keleti E. Experimental osteomyelitis due to Staphylococcus aureus or Pseudomonas aeruginosa: a radiographic-pathological correlative analysis. Br J Exp Pathol, 1980, 61(4): 451-460.
7.	Rissing JP, Buxton TB, Weinstein RS, et al. Model of experimental chronic osteomyelitis in rats. Infect Immun, 1985, 47(3): 581-586.
8.	Smeltzer MS, Thomas JR, Hickmon SG, et al. Characterization of a rabbit model of staphylococcal osteomyelitis. J Orthop Res, 1997, 15(3): 414-421.
9.	Hatzenbuehler J, Pulling TJ. Diagnosis and management of osteomyelitis. Am Fam Physician, 2011, 84(9): 1027-1033.
10.	Popat KC, Eltgroth M, Latempa TJ, et al. Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes. Biomaterials, 2007, 28(32): 4880-4888.
11.	Ince A, Schutze N, Hendrich C, et al. Effect of polyhexanide and gentamycin on human osteoblasts and endothelial cells. Swiss Med Wkly, 2007, 137(9-10): 139-145.
12.	van de Belt H, Neut D, Uges DR, et al. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials, 2000, 21(19): 1981-1987.
13.	Movassaghian S, Moghimi HR, Shirazi FH, et al. Dendrosome-dendriplex inside liposomes: as a gene delivery system. J Drug Target, 2011, 19(10): 925-932.
14.	Halwani M, Yebio B, Suntres ZE, et al. Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. J Antimicrob Chemother, 2008, 62(6): 1291-1297.
15.	Moghimi SM, Porter CJ, Illum L, et al. The effect of poloxamer-407 on liposome stability and targeting to bone marrow:comparison with polystyrene microspheres. Int J Pharnm, 1991, 68(1-3): 121-126.
16.	Kadry AA, Al-Suwayeh SA, Abd-Allah AR, et al. Treatment of experimental osteomyelitis by liposomal antibiotics. J Antimicrob Chemother, 2004, 54(6): 1103-1108.
17.	Trafny EA, Stepinska M, Antos M, et al. Effects of free and liposome-encapsulated antibiotics on adherence of Pseudomonas aeruginosa to collagen type I. Antimicrob Agents Chemother, 1995, 39(12): 2645-2649.
18.	Datta N, Pham QP, Sharma U, et al. In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. Proc Natl Acad Sci U S A, 2006, 103(8): 2488-2493.
19.	Kankilic B, Bayramli E, Kilic E, et al. Vancomycin containing PLLA/β-TCP controls MRSA in vitro. Clin Orthop Relat Res, 2011, 469(11): 3222-3228.
20.	Zhu CT, Xu YQ, Shi J, et al. Liposome combined porous beta-TCP scaffold: preparation, characterization, and anti-biofilm activity. Drug Deliv, 2010, 17(6): 391-398.
21.	Zhou G, Li Y, Zhang L, et al. Preparation and characterization of nano-hydroxyapatite/chitosan/konjac glucomannan composite. J Biomed Mater Res A, 2007, 83(4): 931-939.

1. Gustilo RB, Merkow RL, Templeman D. The management of open fractures. J Bone Joint Surg (Am), 1990, 72(2): 299-304.
2. de Carvalho CC. Biofilms: recent developments on an old battle. Recent Pat Biotechnol, 2007, 1(1): 49-57.
3. Widmer AF. New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis, 2001, 33 Suppl 2: S94-106.
4. Kim HJ, Jones MN. The delivery of benzyl penicillin to Staphylococcus aureus biofilms by use of liposomes. J Liposome Res, 2004, 14(3-4): 123-139.
5. Ma T, Shang BC, Tang H, et al. Nano-hydroxyapatite/chitosan/konjac glucomannan scaffolds loaded with cationic liposomal vancomycin: preparation, in vitro release and activity against Staphylococcus aureus biofilms. J Biomater Sci Polym Ed, 2011, 22(12): 1669-1681.
6. Norden CW, Myerowitz RL, Keleti E. Experimental osteomyelitis due to Staphylococcus aureus or Pseudomonas aeruginosa: a radiographic-pathological correlative analysis. Br J Exp Pathol, 1980, 61(4): 451-460.
7. Rissing JP, Buxton TB, Weinstein RS, et al. Model of experimental chronic osteomyelitis in rats. Infect Immun, 1985, 47(3): 581-586.
8. Smeltzer MS, Thomas JR, Hickmon SG, et al. Characterization of a rabbit model of staphylococcal osteomyelitis. J Orthop Res, 1997, 15(3): 414-421.
9. Hatzenbuehler J, Pulling TJ. Diagnosis and management of osteomyelitis. Am Fam Physician, 2011, 84(9): 1027-1033.
10. Popat KC, Eltgroth M, Latempa TJ, et al. Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes. Biomaterials, 2007, 28(32): 4880-4888.
11. Ince A, Schutze N, Hendrich C, et al. Effect of polyhexanide and gentamycin on human osteoblasts and endothelial cells. Swiss Med Wkly, 2007, 137(9-10): 139-145.
12. van de Belt H, Neut D, Uges DR, et al. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials, 2000, 21(19): 1981-1987.
13. Movassaghian S, Moghimi HR, Shirazi FH, et al. Dendrosome-dendriplex inside liposomes: as a gene delivery system. J Drug Target, 2011, 19(10): 925-932.
14. Halwani M, Yebio B, Suntres ZE, et al. Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. J Antimicrob Chemother, 2008, 62(6): 1291-1297.
15. Moghimi SM, Porter CJ, Illum L, et al. The effect of poloxamer-407 on liposome stability and targeting to bone marrow:comparison with polystyrene microspheres. Int J Pharnm, 1991, 68(1-3): 121-126.
16. Kadry AA, Al-Suwayeh SA, Abd-Allah AR, et al. Treatment of experimental osteomyelitis by liposomal antibiotics. J Antimicrob Chemother, 2004, 54(6): 1103-1108.
17. Trafny EA, Stepinska M, Antos M, et al. Effects of free and liposome-encapsulated antibiotics on adherence of Pseudomonas aeruginosa to collagen type I. Antimicrob Agents Chemother, 1995, 39(12): 2645-2649.
18. Datta N, Pham QP, Sharma U, et al. In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. Proc Natl Acad Sci U S A, 2006, 103(8): 2488-2493.
19. Kankilic B, Bayramli E, Kilic E, et al. Vancomycin containing PLLA/β-TCP controls MRSA in vitro. Clin Orthop Relat Res, 2011, 469(11): 3222-3228.
20. Zhu CT, Xu YQ, Shi J, et al. Liposome combined porous beta-TCP scaffold: preparation, characterization, and anti-biofilm activity. Drug Deliv, 2010, 17(6): 391-398.
21. Zhou G, Li Y, Zhang L, et al. Preparation and characterization of nano-hydroxyapatite/chitosan/konjac glucomannan composite. J Biomed Mater Res A, 2007, 83(4): 931-939.

《中國修復重建外科雜志》

萬古霉素陽離子脂質體復合納米羥基磷灰石/ 殼聚糖/魔芋葡甘聚糖治療兔慢性感染性骨缺損

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《中國修復重建外科雜志》

萬古霉素陽離子脂質體復合納米羥基磷灰石/ 殼聚糖/魔芋葡甘聚糖治療兔慢性感染性骨缺損

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