PREPARATION AND BIOCOMPATIBILITY OF A NOVEL BIOMIMETIC OSTEOCHONDRAL SCAFFOLD: COLLAGEN-CHITOSAN/NANO-HYDROXYAPATITE-COLLAGEN-POLYLACTIC ACID_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LIN Jianhua ¹ , LAI Jianming ² , LIN Wenping ³ , WU Chaoyang ¹ , XU Shenggui ¹

1Department of Orthopedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou Fujian, P.R.China, 350004;;
2Department of Orthopedics, Longyan First Hospital, Fujian Medical University;;
3Department of Orthopedics, the Second Affiliated Hospital, Fujian Medical University. Corresponding author: LIN Jianhua, E-mail: jianhua0918@126.com;

Corresponding author：

Keywords：

Osteochondral tissue engineering; Scaffold; Collagen-chitosan/nano-hydroxyapatite-collagen-polylactic acid biomimetic scaffold; Biocompatibility

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Objective To prepare collagen-chitosan /nano-hydroxyapatite-collagen-polylactic acid (Col-CS/ nHAC-PLA) biomimetic scaffold and to examine its biocompatibility so as to lay the foundation for its application on the treatment of osteochondral defect. Methods PLA was dissolved in dioxane for getting final concentration of 8%, and the nHAC power was added at a weight ratio of nHAC to PLA, 1 ∶ 1. The solution was poured into a mold and frozen. CS and Col were dissolved in 2% acetum for getting the final concentrations of 2% and 1% respectively, then compounded at a weight ratio of CS to Col, 20 ∶ 1. The solution was poured into the frozen mold containing nHAC-PLA, and then biomimetic osteochondral scaffold of Col-CS/nHAC-PLA was prepared by freeze-drying. Acute systemic toxicity test, intracutaneous stimulation test, pyrogen test, hemolysis test, cytotoxicity test, and bone implant test were performed to evaluate its biocompatibility. Results Col-CS/nHAC-PLA had no acute systemic toxicity. Primary irritation index was 0, indicating that Col-CS/nHAC-PLA had very slight skin irritation. In pyrogen test, the increasing temperature of each rabbit was less than 0.6℃, and the increasing temperature sum of 3 rabbits was less than 1.3℃, which was consistent with the evaluation criteria. Hemolytic rate of Col-CS/nHAC-PLA was 1.38% (far less than 5%). The toxicity grade of Col-CS/nHAC-PLA was classified as grade I. Bone implant test showed that Col-CS/nHAC-PLA had good biocompatibility with the surrounding tissue. Conclusion Col-CS/ nHAC-PLA scaffold has good biocompatibility, which can be used as an alternative osteochondral scaffold.

Citation： LIN Jianhua,LAI Jianming,LIN Wenping,WU Chaoyang,XU Shenggui. PREPARATION AND BIOCOMPATIBILITY OF A NOVEL BIOMIMETIC OSTEOCHONDRAL SCAFFOLD: COLLAGEN-CHITOSAN/NANO-HYDROXYAPATITE-COLLAGEN-POLYLACTIC ACID. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(8): 1001-1006. doi: Copy

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25.	杨波, 胡蕴玉, 毕龙, 等. 胶原/羟基磷灰石骨软骨一体化支架的生物学特性研究. 中国矫形外科杂志, 2010, 18(4): 304-307.
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27.	Hench LL, Polak JM. Third-generation biomedical materials. Science. 2002, 295(5557):1014-1017.

1. Hang NB, Zhao JN. The development of scaffolds in cartilage tissue engineering. J Med Postgra, 2010, 23(1): 94-96.
2. Gratz KR, Wong VW, Chen AC, et al. Biomechanical assessment of tissue retrieved after in vivo cartilage defect repair: tensile modulus of repair tissue and integration with host cartilage. J Biomech, 2006, 39(1): 138-146.
3. Zhang Z, McCaffery JM, Spencer RG, et al. Growth and integration of neocartilage with native cartilage in vitro. J Orthop Res, 2005, 23(2): 433-439.
4. Jung Y, Park MS, Lee JW, et al. Cartilage regeneration with highly-elastic three-dimensional scaffolds prepared from biodegradable poly (L-lactide-co-epsilon-caprolactone). Biomaterials, 2008, 29(35): 4630-4636.
5. 张永涛, 金丹. 组织工程骨软骨复合体构建的研究进展. 中国修复重建外科杂志, 2011, 25(9): 1120-1124.
6. 国家医疗器械生物学评价标准化技术委员会. GB/T16886. 医疗器械生物学评价. 北京: 中国标准出版社, 2001: 307-309.
7. International Standard Organization. ISO 10993. Biological evaluation of medical devices. USA: Information Handling Services, 2006: 14-20.
8. Liao SS, Cui FZ, Zhang W, et al. Hierarchically biomimetic bone scaffold materials: nano-HA/collagen/PLA composite. J Biomed Mater Res B Appl Biomater, 2004, 69B(2): 158-165.
9. 单程, 孙晓丹, 战景林. 胶原-壳聚糖制备仿生多层结构软骨支架. 医用生物力学, 2010, 25(1): 26-31.
10. 国家医疗器械生物学评价标准化技术委员会. GB/T16886. 11-1997医疗器械生物学评价——第11部分: 全身毒性实验. 北京: 中国标准出版社, 1997: 4.
11. International standard organization. ISO 10993-11. 2006 Biological evaluation of medical devices—Part 11: Tests for systemic toxicity. USA: Information Handling Services, 2006: 7-11.
12. International standard organization. ISO 10993-10. 2010 Biological evaluation of medical devices—Part 10: Tests for irritation and skin sensitization. USA: Information Handling Services, 2010: 11-13.
13. 国家药典委员会. 中华人民共和国药典: 附录Ⅺ D热原检查法. 北京: 中国医药科技出版社, 2010: 附录99.
14. 孙皎, 顾国珍, 钱云芳. 生物材料不同接触方式和条件对溶血作用影响的研究. 生物医学工程学杂志, 2003, 20(1): 8-10.
15. 张文云, 沈毅, 李南, 等. 牙科纤维/树脂复合材料的生物安全性研究. 解放军医学杂志, 2004, 29(4): 345-347.
16. International standard organization. ISO 10993-5: 2009 Biological evaluation of medical devices—Part 5: Tests for in vitro cytotoxicity. USA: Information Handling Services, 2009: 24-28.
17. Li Y, Liu J, Zhong Y, et al. Biocompatibility of Fe “O”@Au composite magnetic nanoparticles in vitro and in vivo. Int J Nanomedicine, 2011, 6: 2805-2819.
18. International standard organization. ISO 10993-6: 2007 Biological evaluation of medical devices—Part 6: Tests for local effects after implantation. USA: Information Handling Services, 2007: 14-16.
19. Bedi A, Williams III RJ. Cartilage resurfacing using synthetic composite plugs. Tech Knee Surg, 2009, 8(1): 29-36.
20. 刘明, 项舟, 裴福兴, 等. BMSCs种植双相复合支架修复兔关节软骨及软骨下骨缺损. 中国修复重建外科杂志, 2010, 24(1): 87-93.
21. 吴斌, 王黎明, 李煜明. 应用组织工程骨-软骨复合组织块修复猪软骨缺损. 江苏医药, 2011, 37(21): 2505-2508.
22. 冯庆玲, 崔福斋, 张伟. 纳米羟基磷灰石/胶原骨修复材料. 中国医学科学院学报, 2002, 24(2): 124-128.
23. 黄永辉, 沈铁城. 纳米人工骨的研究进展. 江苏大学学报: 医学版, 2005, 15(4): 363-365, 367.
24. 廖素三, 崔福斋, 张伟. 组织工程中胶原基纳米骨修复材料的研制. 中国医学科学院学报, 2003, 25(1): 36-38.
25. 杨波, 胡蕴玉, 毕龙, 等. 胶原/羟基磷灰石骨软骨一体化支架的生物学特性研究. 中国矫形外科杂志, 2010, 18(4): 304-307.
26. Griffith LG, Naughton G. Tissue engineering—Current challenges and expanding opportunities. Science, 2002, 295(5557): 1009-1014.
27. Hench LL, Polak JM. Third-generation biomedical materials. Science. 2002, 295(5557):1014-1017.

Chinese Journal of Reparative and Reconstructive Surgery

PREPARATION AND BIOCOMPATIBILITY OF A NOVEL BIOMIMETIC OSTEOCHONDRAL SCAFFOLD: COLLAGEN-CHITOSAN/NANO-HYDROXYAPATITE-COLLAGEN-POLYLACTIC ACID

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