Sains Malaysiana 50(8)(2021): 2309-2318

http://doi.org/10.17576/jsm-2021-5008-14

 

Vancomycin Loaded Alginate/Cockle Shell Powder Nanobiocomposite Bone Scaffold for Antibacterial and Drug Release Evaluation

(Perancah Tulang Biokomposit-Nano Alginat/Serbuk Cengkerang Kerang yang Mengandungi Vankomisin untuk Sifat Antibakteria dan Penilaian Pembebasan Dadah)

 

SU WEN YUAN1, JACINTA SANTHANAM1, NG SHIOW FERN2 & B. HEMABARATHY BHARATHAM1*

 

1Biomedical Science Programme, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

 

2Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

 

Received: 29 September 2020/Accepted: 12 December 2020

 

ABSTRACT

Bacterial infection and biofilm formation is a major concern in orthopaedic implants and bone reconstructive surgery complications that may be addressed with localized drug delivery system. The potential use of a fabricated nanobiocomposite bone scaffold using alginate and nano cockle shell powder for drug release and antibacterial properties was investigated. Vancomycin loaded bone scaffolds were fabricated with 3 and 5 wt% vancomycin, respectively, while a non-drug loaded scaffold was used as controls. The mineralization of the scaffolds using simulated body fluid (SBF) as well as biofilm formation were evaluated using microscopic observations. Drug release study and antimicrobial activity of the eluent from each sampling period was tested for growth inhibition of Staphylococcus aureus and Staphylococcus epidermidis for a period of 21 days. Significant difference of cumulative amount of vancomycin eluted from scaffolds loaded with 5 wt% vancomycin compared to 3 wt% (p<0.05) were noted. Eluent from both groups showed inhibitory effect against bacterial strain tested for 21 days. The findings are further supported with histological observations of reduced biofilm formation by Staphylococcus epidermidis on surface of 5 wt% vancomycin loaded scaffolds compared to control scaffolds. Basic mineralization studies conducted showed no alteration in drug loaded scaffolds characteristics compared to control scaffolds. Findings from this study indicates antibacterial properties can be conferred to the fabricated bone scaffold with successful incorporation of vancomycin with potentials to be used for local drug delivery application.

Keywords: Antibacterial; bone scaffold; drug elution; nano cockle shell; vancomycin

 

ABSTRAK

Jangkitan bakteria dan pembentukan biofilem merupakan komplikasi utama dalam implantasi ortopedik dan pembedahan pembinaan semula tulang yang boleh ditangani dengan penghantaran dadah secara langsung dan setempat melalui peranti implan. Penyelidikan ini mengkaji pembebasan dadah dan aktiviti antibakteria elusi dadah daripada perancah tulang alginat/serbuk cangkerang kerang yang difabrikasi dengan 3 and 5 %bt vankomisin. Untuk tujuan perbandingan, perancah tulang tanpa vankomisin difabrikasi sebagai kawalan. Aktiviti mineralisasi perancah dalam larutan simulasi cecair badan (SBF) dan pembentukan biofilem pada permukaan perancah diperhatikan dengan kajian mikroskopi. Kajian pembebasan dadah dijalankan dengan merendamkan perancah tulang dalam larutan SBF sebelum menilai jumlah elusi dadah pada tempoh masa tertentu. Aktiviti antibakteria elusi dadah terhadap Staphylococcus aureus dan Staphylococcus epidermidis telah dikaji melalui pembentukan zon perencatan selama 21 hari. Hasil kajian menunjukkan perbezaan yang signifikan pada jumlah elusi dadah dengan jumlah dadah yang dikesan daripada perancah tulang yang difabrikasi dengan 5 %bt vankomisin lebih tinggi daripada 3 %bt (p<0.0.5). Elusi daripada kedua-dua kumpulan perancah tulang menunjukkan kesan aktiviti antibakteria terhadap kedua-dua strain bakteria selama 21 hari. Hasil ini dibuktikan lagi dengan pemerhatian histologi yang menunjukkan pengurangan pembentukan biofilemStaphylococcus epidermidis pada perancah 5 %bt vankomisin. Pemerhatian SEM juga menunjukkan tiada perubahan terhadap ciri-ciri pembentukan mineral pada permukaan perancah yang difabrikasikan dengan dadah berbanding perancah kumpulan kawalan. Hasil kajian ini menunjukkan perancah tulangalginat/serbuk cangkerang kerang yang difabrikasi dengan vankomisin menunjukkan ciri-ciri antibakteria dan berpotensi untuk dibangunkan dalam aplikasi sistem penghantaran dadah.      

Kata kunci: Antibakteria; nano kulit cengkerang; pembebasan dadah; perancah tulang; vankomisin

 

REFERENCES

Abbasi, N., Hamlet, S., Love, R.M. & Nguyen, N.T. 2020. Porous scaffold for bone regeneration. Journal of Science: Advanced Materials and Devices 5(1): 1-9.

Abdelfattah, M.I., Nasry, S.A. & Mostafa, A.A. 2016. Characterization and cytotoxicity analysis of a ciprofloxacin loaded chitosan/bioglass scaffold on cultured human periodontal ligament stem cells: A preliminary report. Open Access Macedonian Journal of Medical Sciences 4(3): 461-467.

Ahmad, N., Bharatham, H., Hamid, Z.A., Perimal, E.K. & George, P. 2019. Functional performance evaluation of an alginate/nano-cockle shell powder nanobiocomposite bone scaffold with BMP-2. Bulletin of Materials Science 42(3): 1-10.

Bharatham, B.H., Bakar, A., Zuki, M., Perimal, E.K., Yusof, L.M. & Hamid, M. 2014.   Development and characterization of novel porous 3D alginate-cockle shell powder nanobiocomposite bone scaffold. BioMed Research International 2014: 146723.

Cao, Z., Jiang, D., Yan, L. & Wu, J. 2017. In vitro and in vivo drug release and antibacterial properties of the novel vancomycin-loaded bone-like hydroxyapatite/poly amino acid scaffold. International Journal of Nanomedicine 12: 1841-1851.

Channasanon, S., Udomkusonsri, P., Chantaweroad, S., Tesavibul, P. & Tanodekaew, S. 2017. Gentamicin released from porous scaffolds fabricated by stereolithography. Journal of Healthcare Engineering 2017: 9547896.

Cheung, G.Y., Rigby, K., Wang, R., Queck, S.Y., Braughton, K.R., Whitney, A.R., Teintze, M., Deleo, F.R. & Otto, M. 2010. Staphylococcus epidermidis strategies to avoid killing by human neutrophils. PLoS Pathogens 6(10): e1001133.

Costa, P.F. 2015.  Bone tissue engineering drug delivery. Curr. Mol. Bio. Rep. 1(2): 87-93.

del Pozo, E.G., Collazos, J., Carton, J.A., Camporro, D. & Asensi, V. 2018. Factors predictive of relapse in adult bacterial osteomyelitis of long bones. BMC Infectious Diseases 18(1): 1-11.

Dorozhkin, S.V. 2011. Self-setting calcium orthophosphate formulations: Cements, concretes, pastes and putties. International Journal of Materials and Chemistry 1(1): 1-48.

George, P., Hamid, Z.A., Zakaria, M.Z.A.B., Perimal, E.K. & Bhatatham, H. 2019. A short review on cockle shells as biomaterials in the context of bone scaffold fabrication. Sains Malaysiana 48(7): 1539-1545.

Gentile, P., Bellucci, D., Sola, A., Mattu, C., Cannillo, V. & Ciardelli, G. 2015. Composite scaffolds for controlled drug release: Role of the polyurethane nanoparticles on the physical properties and cell behaviour. Journal of the Mechanical Behavior of Biomedical Materials 44: 53-60.

Gimeno, M., Pinczowski, P., Pérez, M., Giorello, A., Martínez, M.Á., Santamaría, J., Arruebo, M. & Luján, L. 2015. A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study.  European Journal of Pharmaceutics and Biopharmaceutics 96: 264-271.

Gutiérrez-Prieto, S.J., Perdomo-Lara, S.J., Diaz-Peraza, J.M. & Sequeda-Castañeda, L.G. 2019. Analysis of in vitro ostoeblast culture on scaffolds for future bone regeneration purposes in dentistry. Advances in Pharmacological and Pharmaceutical Sciences 2019: 5420752.

Hemabarathy, B., Md. Zuki, A.B.Z., Perimal, E.K., Yusof, L.Q. & Hamid, M. 2014. Mineral and physiochemical evaluation of cockle shell (Anadara granosa) and other selected molluscan shell as potential biomaterials. Sains Malaysiana 43(7): 1023-1029.

Isa, T., Zakaria, Z.A.B., Rukayadi, Y., Mohd Hezmee, M.N., Jaji, A.Z., Imam, M.U., Hammadi, N.I. & Mahmood, S.K. 2016. Antibacterial activity of ciprofloxacin-encapsulated cockle shells calcium carbonate (aragonite) nanoparticles and its biocompatability in macrophage J774A.1. International Journal of Molecular Sciences 17(5): 713.

Johnson, C.T. & García, A.J. 2015. Scaffold-based anti-infection strategies in bone repair. Annals of Biomedical Engineering 43(3): 515-528.

Kohanski, M.A., Dwyer, D.J. & Collins, J.J. 2010. How antibiotics kill bacteria: From targets to networks. Nature Reviews Microbiology 8(6): 423-435.

Krishnan, A.G., Jayaram, L., Biswas, R. & Nair, M. 2015. Evaluation of antibacterial activity and cytocompatibility of ciprofloxacin loaded gelatin-hydroxyapatite scaffolds as a local drug delivery system for osteomyelitis treatment. Tissue Engineering Part A 21(7-8): 1422-1431.

Lecaroz, C., Gamazo, C. & Blanco-Prieto, M. 2006. Nanocarriers with gentamicin to treat intracellular pathogens. Journal of Nanoscience and Nanotechnology 6(9-10): 3296-3302.

Leekha, S., Terrell, C.L. & Edson, R.S. 2011. General principles of antimicrobial therapy. Mayo Clinic Proceedings 86(2): 156-167.

Luongo, F., Mangano, F.G., Macchi, A., Luongo, G. & Mangano, C. 2016. Custom-made synthetic scaffolds for bone reconstruction: A retrospective, multicenter clinical study on 15 patients.  BioMed Research International 2016: 5862586.

Matsubayashi, M., Terukina, T., Hattori, Y. & Otsuka, M. 2018. Preparation of calcium phosphate coated simvastatin-loaded PLGA microspheres dispersed alginate hydrogel beads as a controlled drug delivery carrier. Key Engineering Materials 782(October): 201-206.

Montanaro, L., Speziale, P., Campoccia, D., Ravaioli, S., Cangini, I., Pietrocola, G., Giannini, S. & Arciola, C.R. 2011. Scenery of staphylococcus implant infections in orthopedics. Future Microbiology 6(11): 1329-1349.

Mouriño, V. & Boccaccini, A.R. 2010. Bone tissue engineering therapeutics: Controlled drug delivery in three-dimensional scaffolds. Journal of the Royal Society Interface 7(43): 209-227.

Parent, M., Magnaudeix, A., Delebassee, S., Sarre, E., Champion, E., Trecant, M.V. & Damia, C. 2016. Hydroxyapatite microporous bioceramics as vancomycin reservoir: Antibacterial efficiency and biocompatibility investigation. Journal of Biomaterials Applications 31(4): 488-498.

Punyani, S., Deb, S. & Singh, H. 2007. Contact killing antimicrobial acrylic bone cements: Preparation and characterization. Journal of Biomaterials Science, Polymer Edition 18(2): 131-145.

Ribeiro, M., Monteiro, F.J. & Ferraz, M.P. 2012. Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions. Biomatter 2(4): 176-194.

Rodriguez, I., Saxena, G., Sell, S. & Bowlin, G. 2014. Mineralization and characterization of composite lyophilized gelatin sponges intended for early bone regeneration. Bioengineering 1(1): 62-84.

Saravanan, S., Nethala, S., Pattnaik, S., Tripathi, A., Moorthi, A. & Selvamurugan, N. 2011. Preparation, characterization and antimicrobial activity of a bio-composite scaffold containing chitosan/nano-hydroxyapatite/nano-silver for bone tissue engineering. International Journal of Biological Macromolecules 49(2): 188-193.

Wu, X., Walsh, K., Hoff, B.L. & Camci-Unal, G. 2020. Mineralization of biomaterials for bone tissue engineering. Bioengineering 7(4): 132.

Yang, Y.H., Wang, J.C. & Pei, Y.L. 2011. Adding vancomycin to bone cement: Research on its influence on mechanical and fixation strength using rabbit femoral prostheses. Orthopaedic Surgery 3(4): 265-267.

Zhang, J., Wang, C., Wang, J., Qu, Y. & Liu, G. 2012. In vivo drug release and antibacterial properties of vancomycin loaded hydroxyapatite/chitosan composite. Drug Delivery 19(5): 264-269.

Zhao, X., Kim, J., Cezar, C.A., Huebsch, N., Lee, K., Bouhadir, K. & Mooney, D.J. 2011. Active scaffolds for on-demand drug and cell delivery. Proceedings of the National Academy of Sciences 108(1): 67-72.

 

*Corresponding author; email: hema@ukm.edu.my

 

     

       

previous