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Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Research article

The chitosan/tri-calcium phosphate bio-composite bone cement promotes better osteo-integration: an in vitro and in vivo study

Authors: Chih-Hsiang Fang, Yi-Wen Lin, Jui-Sheng Sun, Feng-Huei Lin

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

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Abstract

Background

Polymethylmethacrylate bone cement has a variety of applications in orthopedic surgery, but it also has some shortcomings such as high heat generation during polymerization and poor integration with bone tissue. In this study, a bio-composite bone cement composed of tri-calcium phosphate and chitosan as additives to acrylic bone cement was developed. Our hypothesis is that this new bio-composite bone cement has a better osteo-integration than pure polymethyl methacrylate cement.

Methods

Physiological composition, i.e., 65 wt% inorganic and 35 wt% organic components, of tri-calcium phosphate and chitosan contents was selected as degradable additives to replace acrylic bone cement. A series of properties such as exothermic temperature changes, setting time, bio-mechanical characteristics, degradation behaviors, and in vitro cytotoxicity were examined. Preliminary in vivo animal study was also performed.

Results

The results showed that the bio-composite bone cement exhibited lower curing temperature, longer setting time, higher weight loss and porosity after degradation, lower compressive Young’s modulus, and ultimate compressive strength as compared with those of pure polymethyl methacrylate cement. Cell proliferation tests demonstrated that the bio-composite bone cement was non-cytotoxic, and the in vivo tests revealed that was more osteo-conductive.

Conclusions

The results indicated that the modified chitosan/tri-calcium phosphate/polymethyl methacrylate bio-composites bone cement could be degraded gradually and create rougher surfaces that would be beneficial to cell adherence and growth. This new bio-composite bone cement has potential in clinical application. Our future studies will focus on long-term implantation to investigate the stability of the bio-composite bone cement in long-term implantation.
Literature
1.
go back to reference Charnley J. Anchorage of the femoral head prosthesis to the shaft of the femur. J Bone Joint Surg Br. 1960;42-b:28–30.CrossRef Charnley J. Anchorage of the femoral head prosthesis to the shaft of the femur. J Bone Joint Surg Br. 1960;42-b:28–30.CrossRef
2.
go back to reference Kee JR, Mears SC, Edwards PK, Bushmiaer M, Barnes CL. Standardization of acrylic bone cement mixing protocols for total knee arthroplasty results in cost savings. Orthopedics. 2018;41(5):e671–5.CrossRef Kee JR, Mears SC, Edwards PK, Bushmiaer M, Barnes CL. Standardization of acrylic bone cement mixing protocols for total knee arthroplasty results in cost savings. Orthopedics. 2018;41(5):e671–5.CrossRef
3.
go back to reference Ray AK, Romine JS, Pankovich AM. Stabilization of pathologic fractures with acrylic cement. Clin Orthop Relat Res. 1974;(101):182–5. Ray AK, Romine JS, Pankovich AM. Stabilization of pathologic fractures with acrylic cement. Clin Orthop Relat Res. 1974;(101):182–5.
4.
go back to reference Kim YS, Kang YH, Kim JK, Park JB. Effect of bone mineral particles on the porosity of bone cement. Bio-Med Mat Eng. 1994;4(1):37–46. Kim YS, Kang YH, Kim JK, Park JB. Effect of bone mineral particles on the porosity of bone cement. Bio-Med Mat Eng. 1994;4(1):37–46.
5.
go back to reference Lu JX, Huang ZW, Tropiano P, Clouet D’Orval B, Remusat M, Dejou J, Proust JP, Poitout D. Human biological reactions at the interface between bone tissue and polymethylmethacrylate cement. J Mat Sci Mat Med. 2002;13(8):803–9.CrossRef Lu JX, Huang ZW, Tropiano P, Clouet D’Orval B, Remusat M, Dejou J, Proust JP, Poitout D. Human biological reactions at the interface between bone tissue and polymethylmethacrylate cement. J Mat Sci Mat Med. 2002;13(8):803–9.CrossRef
6.
go back to reference Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J. 2000;9(5):445–50.CrossRef Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J. 2000;9(5):445–50.CrossRef
7.
go back to reference Cordova LA, Stresing V, Gobin B, Rosset P, Passuti N, Gouin F, Trichet V, Layrolle P, Heymann D. Orthopaedic implant failure: aseptic implant loosening--the contribution and future challenges of mouse models in translational research. Clin Sci (Lond). 2014;127(5):277–93.CrossRef Cordova LA, Stresing V, Gobin B, Rosset P, Passuti N, Gouin F, Trichet V, Layrolle P, Heymann D. Orthopaedic implant failure: aseptic implant loosening--the contribution and future challenges of mouse models in translational research. Clin Sci (Lond). 2014;127(5):277–93.CrossRef
8.
go back to reference Saleh KJ, El Othmani MM, Tzeng TH, Mihalko WM, Chambers MC, Grupp TM. Acrylic bone cement in total joint arthroplasty: a review. J Orthop Res. 2016;34(5):737–44.CrossRef Saleh KJ, El Othmani MM, Tzeng TH, Mihalko WM, Chambers MC, Grupp TM. Acrylic bone cement in total joint arthroplasty: a review. J Orthop Res. 2016;34(5):737–44.CrossRef
9.
go back to reference Bettencourt A, Calado A, Amaral J, Alfaia A, Vale FM, Monteiro J, Montemor MF, Ferreira MG, Castro M. Surface studies on acrylic bone cement. Int J Pharm. 2004;278(1):181–6.CrossRef Bettencourt A, Calado A, Amaral J, Alfaia A, Vale FM, Monteiro J, Montemor MF, Ferreira MG, Castro M. Surface studies on acrylic bone cement. Int J Pharm. 2004;278(1):181–6.CrossRef
10.
go back to reference Cunin G, Boissonnet H, Petite H, Blanchat C, Guillemin G. Experimental vertebroplasty using osteoconductive granular material. Spine. 2000;25(9):1070–6.CrossRef Cunin G, Boissonnet H, Petite H, Blanchat C, Guillemin G. Experimental vertebroplasty using osteoconductive granular material. Spine. 2000;25(9):1070–6.CrossRef
11.
go back to reference Kim SB, Kim YJ, Yoon TL, et al. The characteristics of a hydroxyapatite-chitosan-PMMA bone cement. Biomaterials. 2004;25(26):5715–23.CrossRef Kim SB, Kim YJ, Yoon TL, et al. The characteristics of a hydroxyapatite-chitosan-PMMA bone cement. Biomaterials. 2004;25(26):5715–23.CrossRef
12.
go back to reference Lai PL, Chen LH, Chen WJ, Chu IM. Chemical and physical properties of bone cement for vertebroplasty. Biom J. 2013;36(4):162–7. Lai PL, Chen LH, Chen WJ, Chu IM. Chemical and physical properties of bone cement for vertebroplasty. Biom J. 2013;36(4):162–7.
13.
go back to reference Lin LC, Chang SJ, Kuo SM, Chen SF, Kuo CH. Evaluation of chitosan/beta-tricalcium phosphate microspheres as a constituent to PMMA cement. J Mat Sci Mat Med. 2005;16(6):567–74.CrossRef Lin LC, Chang SJ, Kuo SM, Chen SF, Kuo CH. Evaluation of chitosan/beta-tricalcium phosphate microspheres as a constituent to PMMA cement. J Mat Sci Mat Med. 2005;16(6):567–74.CrossRef
14.
go back to reference Khandaker M, Vaughan MB, Morris TL, White JJ, Meng Z. Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement. Int J Nanomed. 2014;9:2699–712.CrossRef Khandaker M, Vaughan MB, Morris TL, White JJ, Meng Z. Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement. Int J Nanomed. 2014;9:2699–712.CrossRef
15.
go back to reference Aghyarian S, Rodriguez LC, Chari J, Bentley E, Kosmopoulos V, Lieberman IH4 Rodrigues DC. Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation. J Biomater Appl. 2014;29(5):688-698.CrossRef Aghyarian S, Rodriguez LC, Chari J, Bentley E, Kosmopoulos V, Lieberman IH4 Rodrigues DC. Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation. J Biomater Appl. 2014;29(5):688-698.CrossRef
16.
go back to reference Walsh WR, Svehla MJ, Russell J, Saito M, Nakashima T, Gillies RM, Bruce W, Hori R. Cemented fixation with PMMA or Bis-GMA resin hydroxyapatite cement: effect of implant surface roughness. Biomaterials. 2004;25(20):4929–34.CrossRef Walsh WR, Svehla MJ, Russell J, Saito M, Nakashima T, Gillies RM, Bruce W, Hori R. Cemented fixation with PMMA or Bis-GMA resin hydroxyapatite cement: effect of implant surface roughness. Biomaterials. 2004;25(20):4929–34.CrossRef
17.
go back to reference Vlad MD, Sindilar EV, Mariñoso ML, Poeată I, Torres R, López J, Barracó M, Fernández E. Osteogenic biphasic calcium sulphate dihydrate/iron-modified alpha-tricalcium phosphate bone cement for spinal applications: in vivo study. Acta Biomater. 2010;6(2):607–16.CrossRef Vlad MD, Sindilar EV, Mariñoso ML, Poeată I, Torres R, López J, Barracó M, Fernández E. Osteogenic biphasic calcium sulphate dihydrate/iron-modified alpha-tricalcium phosphate bone cement for spinal applications: in vivo study. Acta Biomater. 2010;6(2):607–16.CrossRef
18.
go back to reference Dalby MJ, Di Silvio L, Harper EJ, Bonfield W. Increasing hydroxyapatite incorporation into poly(methylmethacrylate) cement increases osteoblast adhesion and response. Biomaterials. 2002;23(2):569–76.CrossRef Dalby MJ, Di Silvio L, Harper EJ, Bonfield W. Increasing hydroxyapatite incorporation into poly(methylmethacrylate) cement increases osteoblast adhesion and response. Biomaterials. 2002;23(2):569–76.CrossRef
19.
go back to reference Raftery RM, Woods B, Marques ALP, Moreira-Silva J, Silva TH, Cryan SA, Reis RL, O’Brien FJ. Multifunctional biomaterials from the sea: Assessing the effects of chitosan incorporation into collagen scaffolds on mechanical and biological functionality. Acta Biomater. 2016;43:160–9.CrossRef Raftery RM, Woods B, Marques ALP, Moreira-Silva J, Silva TH, Cryan SA, Reis RL, O’Brien FJ. Multifunctional biomaterials from the sea: Assessing the effects of chitosan incorporation into collagen scaffolds on mechanical and biological functionality. Acta Biomater. 2016;43:160–9.CrossRef
20.
go back to reference Di Martino A, Sittinger M, Risbud MV. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials. 2005;26(30):5983–90.CrossRef Di Martino A, Sittinger M, Risbud MV. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials. 2005;26(30):5983–90.CrossRef
21.
go back to reference Onishi H, Machida Y. Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials. 1999;20(2):175–82.CrossRef Onishi H, Machida Y. Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials. 1999;20(2):175–82.CrossRef
22.
go back to reference Nottrott M, Molster AO, Moldestad IO, Walsh WR, Gjerdet NR. Performance of bone cements: are current preclinical specifications adequate? Acta Orthop. 2008;79(6):826–31.CrossRef Nottrott M, Molster AO, Moldestad IO, Walsh WR, Gjerdet NR. Performance of bone cements: are current preclinical specifications adequate? Acta Orthop. 2008;79(6):826–31.CrossRef
23.
go back to reference Moursi AM, Winnard AV, Winnard PL, Lannutti JJ, Seghi RR. Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite. Biomaterials. 2002;23(1):133–44.CrossRef Moursi AM, Winnard AV, Winnard PL, Lannutti JJ, Seghi RR. Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite. Biomaterials. 2002;23(1):133–44.CrossRef
24.
go back to reference Fernandez de Grado G, Keller L, Idoux-Gillet Y, Wagner Q, Musset AM, Benkirane-Jessel N, Bornert F, Offner D. Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J Tissue Eng. 2018;9:2041731418776819.CrossRef Fernandez de Grado G, Keller L, Idoux-Gillet Y, Wagner Q, Musset AM, Benkirane-Jessel N, Bornert F, Offner D. Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J Tissue Eng. 2018;9:2041731418776819.CrossRef
25.
go back to reference Azevedo AS, Sá MJ, Fook MV, Neto PI, Sousa OB, Azevedo SS, Teixeira MW, Costa FS, Araújo AL. Use of chitosan and beta-tricalcium phosphate, alone and in combination, for bone healing in rabbits. J Mat Sci Mat Med. 2014;25(2):481–6.CrossRef Azevedo AS, Sá MJ, Fook MV, Neto PI, Sousa OB, Azevedo SS, Teixeira MW, Costa FS, Araújo AL. Use of chitosan and beta-tricalcium phosphate, alone and in combination, for bone healing in rabbits. J Mat Sci Mat Med. 2014;25(2):481–6.CrossRef
26.
go back to reference Barralet JE, Gaunt T, Wright AJ, Gibson IR, Knowles JC. Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement. J Biomed Mat Res. 2002;63(1):1–9.CrossRef Barralet JE, Gaunt T, Wright AJ, Gibson IR, Knowles JC. Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement. J Biomed Mat Res. 2002;63(1):1–9.CrossRef
27.
go back to reference Castaldini A, Cavallini A. Setting properties of bone cement with added synthetic hydroxyapatite. Biomaterials. 1985;6(1):55–60.CrossRef Castaldini A, Cavallini A. Setting properties of bone cement with added synthetic hydroxyapatite. Biomaterials. 1985;6(1):55–60.CrossRef
28.
go back to reference Vazquez B, Ginebra MP, Gil X, Planell JA, San Roman J. Acrylic bone cements modified with beta-TCP particles encapsulated with poly(ethylene glycol). Biomaterials. 2005;26(20):4309–16.CrossRef Vazquez B, Ginebra MP, Gil X, Planell JA, San Roman J. Acrylic bone cements modified with beta-TCP particles encapsulated with poly(ethylene glycol). Biomaterials. 2005;26(20):4309–16.CrossRef
29.
go back to reference Mayr-Wohlfart U, Fiedler J, Gunther KP, Puhl W, Kessler S. Proliferation and differentiation rates of a human osteoblast-like cell line (SaOS-2) in contact with different bone substitute materials. J Biomed Mat Res. 2001;57(1):132–9.CrossRef Mayr-Wohlfart U, Fiedler J, Gunther KP, Puhl W, Kessler S. Proliferation and differentiation rates of a human osteoblast-like cell line (SaOS-2) in contact with different bone substitute materials. J Biomed Mat Res. 2001;57(1):132–9.CrossRef
30.
go back to reference Benesch J, Tengvall P. Blood protein adsorption onto chitosan. Biomaterials. 2002;23(12):2561–8.CrossRef Benesch J, Tengvall P. Blood protein adsorption onto chitosan. Biomaterials. 2002;23(12):2561–8.CrossRef
Metadata
Title
The chitosan/tri-calcium phosphate bio-composite bone cement promotes better osteo-integration: an in vitro and in vivo study
Authors
Chih-Hsiang Fang
Yi-Wen Lin
Jui-Sheng Sun
Feng-Huei Lin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1201-2

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