Radiological evaluation of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan composite microspheres combined with coral hydroxyapatite artificial bone in repairing large segmental bone defects_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Zepeng , ZHANG Ying , LIN Zefeng , YE Xiangling , ZHANG Yongqiang ,  XIA Yuanjun , XIA Hong , YIN Qingshui

1. Orthopedic Hospital, Guangzhou General Hospital of Chinese PLA, Guangzhou Guangdong, 510010, P.R.China;
2. Graduate School of Guangzhou University of Chinese Medicine, Guangzhou Guangdong, 510405, P.R.China;

Corresponding?author：

XIA Yuanjun, Email: yuanjunxia@aliyun.com

Keywords：

Dextran sulfate; recombinant human morphogenetic protein 2; chitosan; coralline hydroxyapatite; bone defect; radiology

DOI：

10.7507/1002-1892.201703094

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Objective To evaluate the osteogenic effect of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan (DS/rhBMP-2/CS) combined with coralline hydroxyapatite (CHA) in repairing large segmental bone defects by radiographic feature. Methods Fifty-seven 24-week-old male New Zealand rabbits were prepared for establishing right radius bone defect model of 20 mm in length. In which 54 rabbits were randomly divided into 3 groups (n=18), and the CHA, DS/rhBMP-2/CS/CHA, and rhBMP-2/CHA artificial bone grafts were implanted into the bone defect in groups A, B, and C respectively; the remaining 3 rabbits were implanted nothing as blank control group. After operation, the gross condition of the animals was observed; at 4, 8, and 12 weeks after operation, X-ray film observation, Micro-CT scanning, and three-dimensional reconstruction were performed to obtain the volume of the new bone. Results The experimental animals recovered well and were in normal condition. X-ray observation showed that the bone healing in group B was better than that in groups A and C at each time point. At each time point after operation, the X-ray scores of group B were significantly higher than that of group A and group C (P<0.05); the scores of group C at 8 and 12 weeks after operation were significantly higher than that of group B (P<0.05). Micro-CT scanning and three-dimensional reconstruction observation showed that at each time point after operation in group A, the bone defect area had less bone formation and poor osteogenesis; in group B, there were many new bone tissues in bone defect area, and the bone remodeling was well, and gradually closed to normal bone morphology at 12 weeks; in group C, there were many new bone tissues in bone defect area, but the bone formation was general. The new bone volume of group B was significantly higher than that of group A and group C (P<0.05) at each time point after operation, and the score of group C was higher than that of group A at 8 weeks after operation (P<0.05). Conclusion The osteogenic effect of DS/rhBMP-2/CS/CHA sustained-release artificial bone is much better than that of single CHA and rhBMP-2/CHA, which can provide a new idea for treating bone defect by using bone tissue engineering in the future.

Citation： CHEN Zepeng, ZHANG Ying, LIN Zefeng, YE Xiangling, ZHANG Yongqiang, XIA Yuanjun, XIA Hong, YIN Qingshui. Radiological evaluation of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan composite microspheres combined with coral hydroxyapatite artificial bone in repairing large segmental bone defects. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(11): 1384-1389. doi: 10.7507/1002-1892.201703094 Copy

1.	夏遠軍, 章瑩, 李麗華, 等. rhBMP-2/殼聚糖/硫酸葡聚糖復合微球制備及生物安全性研究. 中國骨科臨床與基礎研究雜志, 2013, 5(6): 345-349.
2.	夏遠軍, 章瑩, 李麗華, 等. 殼聚糖/硫酸葡聚糖/重組人骨形態發生蛋白-2 微球對大鼠骨髓基質干細胞增殖與分化的影響. 中華創傷骨科雜志, 2014, 16(5): 421-426.
3.	夏遠軍. DSs/rh-BMP-2/CS 復合微球的制備及成骨活性研究. 廣州: 南方醫科大學, 2013.
4.	余翔, 夏遠軍, 鄭曉輝, 等. 兩種殼聚糖載 rhBMP-2 納米微球對 SD 大鼠體內異位成骨的影響. 中國臨床解剖學雜志, 2016, 34(4): 412-418.
5.	Mobasseri R, Karimi M, Tian L, et al. Hydrophobic lapatinib encapsulated dextran-chitosan nanoparticles using a toxic solvent free method: fabrication, release property & in vitro anti-cancer activity. Mater Sci Eng C Mater Biol Appl, 2017, 74: 413-421.
6.	Saboktakin MR, Tabatabaie RM, Maharramov A, et al. Synthesis and characterization of pH-dependent glycol chitosan and dextran sulfate nanoparticles for effective brain cancer treatment. Int J Biol Macromol, 2011, 49(4): 747-751.
7.	Chaiyasan W, Srinivas SP, Tiyaboonchai W. Mucoadhesive chitosan-dextran sulfate nanoparticles for sustained drug delivery to the ocular surface. J Ocul Pharmacol Ther, 2013, 29(2): 200-207.
8.	Chaiyasan W, Prapubut S, Kompella UB, et al. Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea. Colloids Surf B Biointerfaces, 2017, 149: 288-296.
9.	Gnanadhas DP, Ben Thomas M, Elango M, et al. Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella. J Antimicrob Chemother, 2013, 68(11): 2576-2586.
10.	Sharma S, Mukkur TK, Benson HA, et al. Enhanced immune response against pertussis toxoid by IgA-loaded chitosan-dextran sulfate nanoparticles. J Pharm Sci, 2012, 101(1): 233-244.
11.	Zaman P, Wang J, Blau A, et al. Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles. Int J Nanomedicine, 2016, 11: 6149-6159.
12.	Costalat M, David L, Delair T. Reversible controlled assembly of chitosan and dextran sulfate: a new method for nanoparticle elaboration. Carbohydr Polym, 2014, 102: 717-726.
13.	Costalat M, David L, Delair T. Reversible controlled assembly of chitosan and dextran sulfate: a new method for nanoparticle elaboration. Carbohydr Polym, 2014, 102: 717-726.
14.	Celik T, Yuksel D, Kosker M, et al. Vascularization of coralline versus synthetic hydroxyapatite orbital implants assessed by gadolinium enhanced magnetic resonance imaging. Curr Eye Res, 2014, 40(3): 346-353.
15.	Yao AH, Li XD, Xiong L, et al. Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery vehicle for rhBMP-2 in the treatment of bone defects. J Mater Sci Mater Med, 2015, 26(1): 5336.
16.	Riley EH, Lane JM, Urist MR, et al. Bone morphogenetic protein-2: biology and applications. Clin Orthop Relat Res, 1996, (324): 39-46.
17.	Katagiri T, Yamaguchi A, Ikeda T, et al. The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun, 1990, 172(1): 295-299.
18.	Hughes FJ, Collyer J, Stanfield M, et al. The effects of bone morphogenetic protein-2, -4, and-6 on differentiation of rat osteoblast cells in vitro. Endocrinology, 1995, 136(6): 2671-2677.
19.	Long MW, Robinson JA, Ashcraft EA, et al. Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors. J Clin Invest, 1995, 95(2): 881-887.
20.	Katagiri T, Yamaguchi A, Komaki M, et al. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol, 1994, 127(6 Pt 1): 1755-1766.
21.	Ho ST, Hutmacher DW. A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials, 2006, 27(8): 1362-1376.
22.	李東亞, 鄭欣, 邱旭升, 等. 兔橈骨骨缺損動物模型中骨缺損長度及缺損位置的影像學比較研究. 中國矯形外科雜志, 2014, 22(8): 737-741.
23.	周芳, 李靜, 余磊, 等. 兔橈骨臨界骨缺損模型的制備. 中國組織工程研究與臨床康復, 2011, 15(50): 9385-9388.

1. 夏遠軍, 章瑩, 李麗華, 等. rhBMP-2/殼聚糖/硫酸葡聚糖復合微球制備及生物安全性研究. 中國骨科臨床與基礎研究雜志, 2013, 5(6): 345-349.
2. 夏遠軍, 章瑩, 李麗華, 等. 殼聚糖/硫酸葡聚糖/重組人骨形態發生蛋白-2 微球對大鼠骨髓基質干細胞增殖與分化的影響. 中華創傷骨科雜志, 2014, 16(5): 421-426.
3. 夏遠軍. DSs/rh-BMP-2/CS 復合微球的制備及成骨活性研究. 廣州: 南方醫科大學, 2013.
4. 余翔, 夏遠軍, 鄭曉輝, 等. 兩種殼聚糖載 rhBMP-2 納米微球對 SD 大鼠體內異位成骨的影響. 中國臨床解剖學雜志, 2016, 34(4): 412-418.
5. Mobasseri R, Karimi M, Tian L, et al. Hydrophobic lapatinib encapsulated dextran-chitosan nanoparticles using a toxic solvent free method: fabrication, release property & in vitro anti-cancer activity. Mater Sci Eng C Mater Biol Appl, 2017, 74: 413-421.
6. Saboktakin MR, Tabatabaie RM, Maharramov A, et al. Synthesis and characterization of pH-dependent glycol chitosan and dextran sulfate nanoparticles for effective brain cancer treatment. Int J Biol Macromol, 2011, 49(4): 747-751.
7. Chaiyasan W, Srinivas SP, Tiyaboonchai W. Mucoadhesive chitosan-dextran sulfate nanoparticles for sustained drug delivery to the ocular surface. J Ocul Pharmacol Ther, 2013, 29(2): 200-207.
8. Chaiyasan W, Prapubut S, Kompella UB, et al. Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea. Colloids Surf B Biointerfaces, 2017, 149: 288-296.
9. Gnanadhas DP, Ben Thomas M, Elango M, et al. Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella. J Antimicrob Chemother, 2013, 68(11): 2576-2586.
10. Sharma S, Mukkur TK, Benson HA, et al. Enhanced immune response against pertussis toxoid by IgA-loaded chitosan-dextran sulfate nanoparticles. J Pharm Sci, 2012, 101(1): 233-244.
11. Zaman P, Wang J, Blau A, et al. Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles. Int J Nanomedicine, 2016, 11: 6149-6159.
12. Costalat M, David L, Delair T. Reversible controlled assembly of chitosan and dextran sulfate: a new method for nanoparticle elaboration. Carbohydr Polym, 2014, 102: 717-726.
13. Costalat M, David L, Delair T. Reversible controlled assembly of chitosan and dextran sulfate: a new method for nanoparticle elaboration. Carbohydr Polym, 2014, 102: 717-726.
14. Celik T, Yuksel D, Kosker M, et al. Vascularization of coralline versus synthetic hydroxyapatite orbital implants assessed by gadolinium enhanced magnetic resonance imaging. Curr Eye Res, 2014, 40(3): 346-353.
15. Yao AH, Li XD, Xiong L, et al. Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery vehicle for rhBMP-2 in the treatment of bone defects. J Mater Sci Mater Med, 2015, 26(1): 5336.
16. Riley EH, Lane JM, Urist MR, et al. Bone morphogenetic protein-2: biology and applications. Clin Orthop Relat Res, 1996, (324): 39-46.
17. Katagiri T, Yamaguchi A, Ikeda T, et al. The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun, 1990, 172(1): 295-299.
18. Hughes FJ, Collyer J, Stanfield M, et al. The effects of bone morphogenetic protein-2, -4, and-6 on differentiation of rat osteoblast cells in vitro. Endocrinology, 1995, 136(6): 2671-2677.
19. Long MW, Robinson JA, Ashcraft EA, et al. Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors. J Clin Invest, 1995, 95(2): 881-887.
20. Katagiri T, Yamaguchi A, Komaki M, et al. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol, 1994, 127(6 Pt 1): 1755-1766.
21. Ho ST, Hutmacher DW. A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials, 2006, 27(8): 1362-1376.
22. 李東亞, 鄭欣, 邱旭升, 等. 兔橈骨骨缺損動物模型中骨缺損長度及缺損位置的影像學比較研究. 中國矯形外科雜志, 2014, 22(8): 737-741.
23. 周芳, 李靜, 余磊, 等. 兔橈骨臨界骨缺損模型的制備. 中國組織工程研究與臨床康復, 2011, 15(50): 9385-9388.

Chinese Journal of Reparative and Reconstructive Surgery

Radiological evaluation of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan composite microspheres combined with coral hydroxyapatite artificial bone in repairing large segmental bone defects

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