https://orcid.org/0000-0001-5759-7926
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Abstract
Background and objective:
Tetracycline and its derivatives, combined with calcium phosphates, have been proposed as a delivery system to control inflammatory processes and chronic infections. The objective of this study was to evaluate the microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite (CHAMINO) as a biomimetic device to carry out target-controlled drug delivery for alveolar bone repair.
Methods:
CHAMINO microspheres were implanted in a rat central incisor socket after 7 and 42 days. New bone was formed in both groups between 7 and 42 days of implantation. However, the bone growth was significantly higher for the CHAMINO microspheres.
Results:
The minocycline (MINO) loading capacity of the nanocrystaline carbonated hydroxyapatite (CHA) nanoparticles was 25.1±2.2 µg MINO/mg CHA for adsorption over 24 hrs. The alginate microspheres containing minocycline-loaded CHA were biologically active and inhibited the Enterococcus faecalis culture growth for up to seven days of the MINO release. An osteoblastic cell viability assay based on the resazurin reduction was conducted after the cells were exposed to the CHAMINO powder and CHAMINO microspheres. Thus, it was found that the alginate extracts encapsulated the minocycline-loaded CHA microspheres and did not affect the osteoblastic cell viability, while the minocycline-doped CHA powder reduced the cell viability by 90%.
Conclusion:
This study concluded that the alginate microspheres encapsulating the minocycline-loaded nanocrystalline carbonated hydroxyapatite exhibited combined antibacterial activity against Enterococcus faecalis with cytocompatibility and osteoconduction properties. The significant improvement in the new bone formation after 42 days of implantation suggests that the CHAMINO microsphere has potential in clinical applications of bone regeneration.
Acknowledgments
This study was supported by the Brazilian financial agencies of National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq]; grant nos 457541/2013-0 and 467513/2014-7), Foundation for Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro [FAPERJ]; grant nos E-26/102.993/2012 and E-26/203.012/2016), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES) (Finance Code 001), and National Institute of Science and Technology on Regenerative Medicine (Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa [INCT Regenera]). The authors wish to thank the IMX beamline of the Brazilian Synchrotron Light Laboratory (LNLS), where the microtomography analyses were performed. We thank Dr Carlos Perez and Helder Valiense from LNLS (XRF Beamline) and Fluminense Federal University (UFF), respectively, for their invaluable contributions to this study.
Disclosure
The authors report no conflicts of interest in this work.
Supplementary materials
Figure S1 Equivalent pore diameter distribution of nanocrystalline carbonated hydroxyapatite (CHA) microsphere determined by SR-µCT.
Abbreviations: SR-µCT, synchrotron radiation-based X ray microtomography.
Figure S2 (A) One-week nanocrystalline carbonated hydroxyapatite (CHA) and (B) minocycline-loaded nanocristalline carbonated hydroxyapatite (CHAMINO) groups. After one week of implantation, the presence of non-degraded CHA microspheres was observed surrounded by connective tissue and with newly formed bone in the CHAMINO group. Magnification: 40×; stain: Hematoxylin and Eosin.
Abbreviations: B, biomaterial; NFB, newly formed bone; CT, connective tissue.
