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, microcomputed 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.

Rose Bengal Crosslinking to Stabilize Collagen Sheets and Generate Modulated Collagen Laminates

“…Singh et al [ 54 ] demonstrated that active agents were released much slower from underloaded matrices compared to those loaded to capacity or overloaded. However, vancomycin has not been observed to bind to collagen [ 55 ], meaning that the loading capacities for vancomycin were well exceeded by the amounts used in our study, and no sustained release was to be expected. In all of our experiments only 80–90% of the vancomycin could be recovered after 24 h. This could not be attributed to vancomycin interaction with the used plasticware (data not shown).…”

Efficacy of Antibiotic‐Loaded Hydroxyapatite/Collagen Composites Is Dependent on Adsorbability for Treating Staphylococcus aureus Osteomyelitis in Rats

“…The electrostatic energy of HAp was reported to play a role in the interaction between drugs and the HAp surface . Given that the surface of c plane of HAp is negatively charged, cationic VCM can adsorb onto HAp because the amino groups of the VCM are protonated . As TEIC resembles the structure as VCM as they both are glycopeptide antibiotics, charge‐based interactions may likewise account for TEIC high adsorbability to HAp .…”

Continuous-flow precipitation as a route to prepare highly controlled nanohydroxyapatite:in vitromineralization and biological evaluation

“…For instance, nanosized HAp demonstrates great potential as delivery vehicle for molecules such as proteins, drugs and DNA [11,13]. Besides its established biocompatibility [13,14], its high specific surface area and high surface reactivity promote an easy binding of great amount of molecules through simple adsorption [15][16][17]. In addition, its small size precludes immune system activation [13].…”