Effect of poly-L-lactic acid/amorphous calcium phosphate scaffold on the surrounding tissue calcification after implantation into the rats

doi:10.3969/j.issn.2095-4344.2015.30.017

Abstract

Abstract:

Abstract
BACKGROUND: Novel fully biodegradable poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffold shows a good prospect of application, but whether the scaffold material has impact on the surrounding tissue calcification is unknown.
OBJECTIVE: To observe the influence of PLLA/ACP scaffold material on the calcification of surrounding tissue after implantation of PLLA/ACP scaffold into rats.
METHODS: A total of 48 SD rats were divided into experimental group and control group randomly. The experimental group was implanted with PLLA/ACP scaffold material, while the control group was implanted with PLLA scaffold material. At 1, 2, 4, 12 weeks after implantation, the liver function, kidney function and concentrations of calcium, phosphorus, alkaline phosphatase in serum were detected; the muscle tissue around the scaffold was collected for hematoxylin-eosin staining, Von Kossa staining, alkaline phosphatase staining and immunohistochemical staining of nuclear factor-kappa B. Then, western blot assay was used to detect the contents of interleukin-6, bone morphogenetic protein-2, and meanwhile, the contents of calcium and alkaline phosphatase in tissue homogenate were measured.
RESULTS AND CONCLUSION: There was no significant difference in either group about the liver and kidney functions at each time. The content of interleukin-6 in the experimental group was less than that in the control
group at 2, 4 and 12 weeks after implantation (P < 0.05). The positive expression of nuclear factor-kappa B, bone morphogenetic protein-2 and inflammatory cell count in the experimental group were less than those in the control group at 4 and 12 weeks after implantation (P < 0.05). The content of calcium in the experimental group was less than that in the control group at 12 weeks after implantation (P < 0.05). No difference was found in the expression of alkaline phosphate, the Von Kossa staining and the content of calcium, phosphorus, alkaline phosphatase in the muscle tissue around the scaffold between the two groups (P > 0.05). These findings indicate that the PLLA/ACP scaffold has a good biocompatibility and biological security, which cannot induce peripheral tissue calcification.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Calcium Phosphates, lkaline Phosphatase, Interleukin-6

CLC Number:

R318

Qin Chao-shi, Li Xiao-yan, Feng Gao-ke, Jiang Xue-jun, Lu Zhao, Li Jun. Effect of poly-L-lactic acid/amorphous calcium phosphate scaffold on the surrounding tissue calcification after implantation into the rats[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(30): 4842-4848.

Figures/Tables 11

References

[1] 肖越勇,.张金山,崔福斋,等.新型生物可降解高分子支架[J].中国医疗器械信息,2004,10(2):12-15.
[2] Serruys PW,Onuma Y,Dudek D,et al.Evaluation of the second generation of a bioresorbable everolimus-eluting vascular scaffold for the treatment of de novo coronary artery stenosis: 12-month clinical and imaging outcomes. J Am Coll Cardiol. 2011;58(15):1578-1588.
[3] Lincoff AM,Furst JG,Ellis SG,et al.Sustained local delievery of dexamethasone by a novel intravascular eluting stent to prevent restenosis in the porcine coronary injury model.J Amcoll Cardic. 1997;29(4):808-816.
[4] Chang EJ, Kim HH, Huh JE,et al.Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling. Exp Cell Res.2005; 303(1):197-206.
[5] Commandeur S,van Beusekom HM,van der Giessen WJ.Polymers, drug release, and drug-eluting stents.J Interv Cardiol.2006;19 (6):500-506.

[6] 卢钊,蒋学俊,冯高科,等.生物全降解药物支架植入小型猪冠状动脉:安全性及组织相容性[J]. 中国组织工程研究,2014,18(34): 5429-5433.
[7] 贺素媛,李虎,任珊,等.新型生物全降解药物释放支架对小型实验猪冠状动脉内膜的影响[J].中国介入心脏病学杂志,2013,21(3): 178-183.
[8] 冯高科,蒋学俊,郑晓新,等.新型生物全降解药物支架对小型猪冠状动脉内皮修复的影响[J]. 武汉大学学报:医学版,2013,34(6): 822-826.
[9] 李虎,李晓艳,蒋学俊,等.新型生物全降解药物支架植入小型猪冠状动脉的安全性[J]. 中国组织工程研究,2013,17(38): 6773- 6778.
[10] Zheng X,Wang Y,Lan Z,et al.Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.J Biomed Nanotechnol.2014; 10(6):900-910.
[11] Lan Z,Lyu Y,Xiao J,et al.Novel biodegradable drug-eluting stent composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles demonstrates improved structural and functional performance for coronary artery disease.J Biomed Nanotechnol.2014;10(7):1194-1204.
[12] Cushman M,Arnold AM,Psaty BM, et al.C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. Circulation. 2005;112(1):25-31.
[13] Pepys MB,Hirschfield GM,Tennent GA,et al.Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006; 440(7088):1217-1221.
[14] Mallavia B, Recio C,Oguiza A, et al.Peptide inhibitor of NF-kappaB translocation ameliorates experimental atherosclerosis. Am J Pathol.2013;182(5):1910-1921.
[15] Hirose K,Iwabuchi K,Shimada K,et al.Different responses to oxidized low-density lipoproteins in human polarized macrophages.Lipids Health Dis.2011;10:1.
[16] Ong AT,McFadden EP,Regar E,et al.Late angiographic stent thrombosis (LAST) events with drug-eluting stents. J Am Coll Cardiol.2005;45(12):2088-2092.
[17] 秦超师,冯高科,李晓艳,等.无定形磷酸钙应用在生物医学中的特点[J].中国组织工程研究,2014,18(39):6353-6357.
[18] 覃春美.骨形态发生蛋白2与血管钙化的相关性研究进展[J].山东医药,2014,54(26): 97-99.
[19] Shioi A,Katagi M, Okuno Y,et al.Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells: roles of tumor necrosis factor-alpha and oncostatin M derived from macrophages.Circ Res.2002;91(1):9-16.
[20] Tintut Y, Patel J, Parhami F, et al.Tumor necrosis factor-alpha promotes in vitro calcification of vascular cells via the cAMP pathway.Circulation.2000;102(21):2636-2642.
[21] Tintut Y, Patel J, Territo M, et al.Monocyte/macrophage regulation of vascular calcification in vitro.Circulation. 2002; 105(5):650-655.
[22] Moe SM,Chen NX.Inflammation and vascular calcification. Blood Purif.2005;23 (1):64-71.