title: Heparinized nanohydroxyapatite/collagen granules for controlled release of vancomycin.
abstract: The purpose of this study was to develop a bone substitute material capable of preventing or treating osteomyelitis through a sustainable release of vancomycin and simultaneously inducing bone regeneration. Porous heparinized nanohydroxyapatite (nanoHA)/collagen granules were characterized using scanning electron microscopy, micro-computed tomography and attenuated total reflectance Fourier transform infrared spectroscopy. After vancomycin adsorption onto the granules, its releasing profile was studied by UV molecular absorption spectroscopy. The heparinized granules presented a more sustainable release over time, in comparison with nonheparinized nanoHA and nanoHA/collagen granules. Vancomycin was released for 360 h and proved to be bioactive until 216 h. Staphylococcus aureus adhesion was higher on granules containing collagen, guiding the bacteria to the material with antibiotic, improving their eradication. Moreover, cytotoxicity of the released vancomycin was assessed using osteoblast cultures, and after 14 days of culture in the presence of vancomycin, cells were able to remain viable, increasing their metabolic activity and colonizing the granules, as observed by scanning electron microscopy and confocal laser scanning microscopy. These findings suggest that heparinized nanoHA/collagen granules are a promising material to improve the treatment of osteomyelitis, as they are capable of releasing vancomycin, eliminating the bacteria, and presented morphological and chemical characteristics to induce bone regeneration.
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4099-002, Portugal.|INEB-Instituto de Engenharia Biomédica, Divisão de Biomateriais, Universidade do Porto, Rua do Campo Alegre 823, Porto, 4150-180, Portugal.|Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e de Materiais, Universidade do Porto, Rua Roberto Frias S/N, Porto, 4200-465, Portugal.
authors.forename: Catarina C
authors.initials: CC
authors.lastname: Coelho
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4099-002, Portugal.|INEB-Instituto de Engenharia Biomédica, Divisão de Biomateriais, Universidade do Porto, Rua do Campo Alegre 823, Porto, 4150-180, Portugal.|REQUIMTE, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Rua Dr, António Bernardino de Almeida 431, Porto, 4200-072, Portugal.
authors.forename: Susana R
authors.initials: SR
authors.lastname: Sousa
authors.affiliation: i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4099-002, Portugal.|INEB-Instituto de Engenharia Biomédica, Divisão de Biomateriais, Universidade do Porto, Rua do Campo Alegre 823, Porto, 4150-180, Portugal.|Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e de Materiais, Universidade do Porto, Rua Roberto Frias S/N, Porto, 4200-465, Portugal.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Monteiro
mesh_terms: D003094:Collagen / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000254:growth & development*; D014640:Vancomycin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D014640:Vancomycin; D003094:Collagen; D017886:Durapatite
keywords: collagen; heparin; nanohydroxyapatite; osteomyelitis; vancomycin