IN VlVO EXPERIMENT OF POROUS BIOACTIVE BONE CEMENT MODIFIED BY BIOGLASS AND CHITOSAN_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Yang ¹ , LEI Wei ¹ , WANG Zheng ² , ZHANG Yi ¹ , NIU Erlong ¹ , YU Long ¹ , WU Jianwei ¹ , ZANG Yuan ¹ , LIU Zhichen ¹ , WU Zixiang ¹

1Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi’an Shaanxi, 710032, P.R.China;;
2Institute of Orthopedics, General Hospital of Chinese PLA. Corresponding author: WU Zixiang, E-mail: wuzixiang@fmmu.edu.cn;

Corresponding author：

Keywords：

Porous bioactive bone cement; Polymethylmethacrylate; Bioglass; Chitosan; Biocompati-bility; Biomechanics; Rabbit

DOI：

10.7507/1002-1892.20130074

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Objective To investigate the biomechanical properties of porous bioactive bone cement (PBC) in vivo and to observe the degradation of PBC and new bone formation histologically. Methods According to the weight percentage (W/ W, %) of polymethylmethacrylate (PMMA) to bioglass to chitosan, 3 kinds of PBS powders were obtained: PBC I (50 ︰ 40 ︰ 10), PBC II (40 ︰ 50 ︰ 10), and PBC III (30 ︰ 60 ︰ 10). The bilateral femoral condylar defect model (4 mm in diameter and 10 mm in depth) was established in 32 10-month-old New Zealand white rabbits (male or female, weighing 4.0-4.5 kg), which were randomly divided into 4 groups (n=8); pure PMMA (group A), PBC I (group B), PBC II (group C), and PBC III (group D) were implanted in the bilateral femoral condylar defects, respectively. Gross observation were done after operation. X-ray films were taken after 1 week. At 3 and 6 months after operation, the bone cement specimens were harvested for mechanical test and histological examination. Four kinds of unplanted cement were also used for biomechanical test as control. Results All rabbits survived to the end of experiment. The X-ray films revealed the location of bone cement was at the right position after 1 week. Before implantation, at 3 months and 6 months after operation, the compressive strength and elastic modulus of groups C and D decreased significantly when compared with those of group A (P lt; 0.05), but no significant difference was found between groups C and D (P gt; 0.05); the compressive strength at each time point and elastic modulus at 3 and 6 months of group B decreased significantly when compared with those of group A (P lt; 0.05). Before implantation and at 3 months after operation, the compressive strength and elastic modulus of groups C and D decreased significantly when compared with those of group B (P lt; 0.05); at 6 months after operation, the compressive strength of group C and the elastic modulus of group D were significantly lower than those of group B (P lt; 0.05). The compressive strength and elastic modulus at 3 and 6 months after operation significantly decreased when compared with those before implantation in groups B, C, and D (P lt; 0.05), but no significant difference was found in group A (P lt; 0.05). At 3 months after operation, histological observation showed that a fibrous tissue layer formed between the PMMA cement and bone in group A, while chitosan particles degraded with different levels in groups B, C, and D, especially in group D. At 6 months after operation, chitosan particles partly degraded in groups B, C, and D with an amount of new bone ingrowth, and groups C and D was better than group B in bone growth; group A had no obvious change. Quantitative analysis results showed that the bone tissue percentage was gradually increased in the group A to group D, and the bone tissue percentage at 6 months after operation was significantly higher than that at 3 months within the group. Conclusion According to the weight percentage (W/W, %) of PMMA to bioglass to chitosan, PBCs made by the composition of 40 ︰ 50 ︰ 10 and 30 ︰ 60 ︰ 10 have better biocompatibility and biomechanical properties than PMMA cement, it may reduce the fracture risk of the adjacent vertebrae after vertebroplasty.

Citation： LI Yang,LEI Wei,WANG Zheng,ZHANG Yi,NIU Erlong,YU Long,WU Jianwei,ZANG Yuan,LIU Zhichen,WU Zixiang. IN VlVO EXPERIMENT OF POROUS BIOACTIVE BONE CEMENT MODIFIED BY BIOGLASS AND CHITOSAN. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(3): 320-325. doi: 10.7507/1002-1892.20130074 Copy

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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