The Effect of Glutaraldehyde on Hydroxyapatite-Gelatin Composite with Addition of Alendronate for Bone Filler Application


Article Preview

Based on data from Indonesian Health Ministry in 2009, osteoporosis case reached 19,7 % of the populations in Indonesia, especially women in menopause period. The treatment was performed by consuming bisphosphonate drugs per oral which was not effective since the absorption intake of the drug was only less than 55% of the intake dosage. Because of that, the bone filler which also has a function as drug delivery system was developed. The hydroxyapatite-gelatin bone filler with the addition of alendronate was studied. To increase the characteristics of this bone filler, glutaraldehyde was introduced in the composite as a crosslinking agent. The concentration of 0.25%, 0.5%, and 0.75% were used. The bone filler was then characterized based on FTIR test, morphology test, compressive strength test, cytotoxicity test, and degradation test. The FTIR result showed that there was no significant difference between the sample with and without glutaraldehyde since the crosslinking bond of glutaraldehyde and gelatin was C=N bond which also presented in the gelatin. The morphology of the samples depicted a bigger pore size for higher glutaraldehyde concentration which also supported by lower compressive strength. All the samples were non-toxic based on the cytotoxicity test which had cell viability more than 100%. The degradation tests showed that with the presence of glutaraldehyde in the bone filler could maintain its form longer than the bone filler without glutaraldehyde. In conclusion, the presence of glutaraldehyde could increase the characteristics of the hydroxyapatite-gelatin composite with the addition of alendronate as a bone filler candidate for osteoporotic bone.





A. P. Putra et al., "The Effect of Glutaraldehyde on Hydroxyapatite-Gelatin Composite with Addition of Alendronate for Bone Filler Application", Journal of Biomimetics, Biomaterials and Biomedical Engineering, Vol. 37, pp. 107-116, 2018

Online since:

June 2018




* - Corresponding Author

[1] International Osteoporosis Foundation, THE ASIA-PACIFIC REGIONAL AUDIT: Epidemiology, costs & burden of osteoporosis in 2013 - Indonesia Country Overview, Hong Kong, (2013).

[2] C. T. Liu, X. J. Yuan, and G. C. Gao, Effects of alendronate on osteoporosis treatment and levels of related cytokines,, Genet. Mol. Res., vol. 16, no. 1, (2017) p.1–9.

[3] R. Dorati et al., Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy.,, Pharmaceuticals (Basel)., vol. 10, no. 4 (2017).


[4] J. A. Sterling and S. A. Guelcher, Biomaterial scaffolds for treating osteoporotic bone,, Current osteoporosis reports, vol. 12, no. 1. (2014) p.48–54.


[5] Z. Noor, Nanohydroxyapatite application to osteoporosis management,, J. Osteoporos., vol. 2013 (2013).

[6] A. S. Budiatin, M. Zainuddin, and J. Khotib, Biocompatable composite as gentamicin delivery system for osteomyelitis and bone regeneration,, Int. J. Pharm. Pharm. Sci., vol. 6, no. 3, (2014) p.223–226.

[7] ASTM C-39, Standard Test Method for Compressive Strength of Cylindrical Concrete Specimens 1,, (2005).

[8] M. C. Chang, C. C. Ko, and W. H. Douglas, Conformational change of hydroxyapatite/gelatin nanocomposite by glutaraldehyde,, Biomaterials, vol. 24, no. 18, (2003) p.3087–3094.


[9] M. K. Narbat, F. Orang, M. S. Hashtjin, and A. Goudarzi, Fabrication of Porous Hydroxyapatite-Gelatin Composite Scaffolds for Bone Tissue Engineering,, Iran. Biomed. J., vol. 10, no. October (2006) p.215–223.

[10] M. Azami, R. Mohammad, and M. Fathollah, Gelatin/hydroxyapatite nanocomposite scaffolds for bone repair,, Soc. Plast. Eng. Plast. Res. Online, vol. 1621, (2016) p.36–43.

[11] Y. Yang, A. C. Ritchie, and N. M. Everitt, Comparison of glutaraldehyde and procyanidin cross-linked scaffolds for soft tissue engineering,, Mater. Sci. Eng. C, vol. 80, (2017) p.263–273.


[12] K. C. Rani, R. Primaharinastiti, and E. Hendradi, Preparation and evaluation of ciprofloxacin implants using bovine hydroxyapatite-chitosan composite and glutaraldehyde for osteomyelitis,, Int. J. Pharm. Pharm. Sci., vol. 8, no. 1, (2016).

[13] S. G., T. Mitra, S. Chatterjee, and A. Gnanamani, Chemistry Behind the Elastic Nature of the Biomaterial Prepared Using Oxidized Form of Glutaraldehyde and Chitosan - an Approach At 2D and 3D Level,, Int. J. Life Sci. Med. Res., vol. 3, no. 2, (2013).


[14] K. Maji and S. Dasgupta, Hydroxyapatite-Chitosan and Gelatin Based Scaffold for Bone Tissue Engineering,, Trans. Indian Ceram. Soc., vol. 73, no. 2 (2014) p.110–114.


[15] E. M. M. Van Lieshout, G. H. Van Kralingen, Y. El-Massoudi, H. Weinans, and P. Patka, Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery,, BMC Musculoskelet. Disord., vol. 12, no. 1, (2011).


[16] C. Khoswanto, E. Arijani, and P. Soesilawati, Cytotoxicity test of 40, 50 and 60% citric acid as dentin conditioner by using MTT assay on culture cell line,, Dent. J. (Majalah Kedokt. Gigi), vol. 41, no. 3, (2008) p.103.


[17] A. Kováčik et al., Influence of Gentamicin on the Specific Cell Culture (Bhk-21) in Vitro,, J. Microbiol. Biotechnol. Food Sci., vol. 6, no. 3, (2016) p.983–986.

[18] M. Azami, M. Rabiee, and F. Moztarzadeh, Glutaraldehyde crosslinked gelatin/hydroxyapatite nanocomposite scaffold, engineered via compound techniques,, Polym. Compos., vol. 31, no. 12, (2010) p.2112–2120.


[19] E. W. Bachtiar, L. R. Amir, P. Suhardi, and B. Abas, Scaffold degradation during bone tissue reconstruction in Macaca nemestrina mandible,, Interventional Medicine & Applied Science, vol. 8, no. 2. Budapest, (2016) p.77–81.


[20] R. Dinarvand, S. Mahmoodi, E. Farboud, M. Salehi, and F. Atyabi, Preparation of gelatin microspheres containing lactic acid--effect of cross-linking on drug release.,, Acta Pharm., vol. 55, no. 1, (2005) p.57–67.

[21] I. H. Kalfas, Principles of bone healing,, Neurosurg. Focus, vol. 10, no. 4, (2001) p.1–4.