Despite the advancements in bone transplantation operations, inflammation is still a serious problem that threatens human health at the post-implantation period. Conventional antibiotic therapy methods may lead to some side effects such as ototoxicity and nephrotoxicity, especially when applied in high doses. Therefore, local drug delivery systems play a vital role in bone disorders due to the elimination of the disadvantages introduced by conventional methods. In the presented study, it was aimed to develop Vancomycin (VC) and Gentamicin (GC) loaded chitosan-montmorillonite nanoclay composites (CS/MMT) to provide required antibiotic doses to combat post-implantation infection. CS/MMT nanocomposite formation was supplied by microfluidizer homogenization and spherical drug carrier nanoparticles were obtained by electrospraying technique. Three factors; voltage, distance and flowrate were varied to fabricate spherical nanoparticles with uniform size. Emprical model was developed to predict nanosphere size by altering process variables. Nanospheres were characterized in terms of morphology, hydrodynamic size, zeta potential, drug encapsulation efficiency and release profile. Drug loaded nanospheres have been successfully produced with a size range of 180-350 nm. Nanocomposite drug carriers showed high encapsulation efficiency (80-95%) and prolonged release period when compared to bare chitosan nanospheres. The drug release from nanocomposite carriers was monitored by diffusion mechanism up to 30 days. The in vitro release medium of nanospheres showed strong antimicrobial activity against gram-positive S. aureus and gram-negative E. coli bacteria. Furthermore, it was found that the nanospheres did not show any cytotoxic effect to fibroblast (NIH/3T3) and osteoblast (SaOS-2) cell lines. The results demonstrated that the prepared composite nanospheres can be a promising option for bone infection prevention at the post implantation period.

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Although nanofillers contribute to improved physical characteristics and biological functionalities of polymer-based biomaterials, their dispersion in polymer matrices is still a challenging issue in terms of obtaining consistency for the inherent properties. To tackle this problem, homogenization techniques are applied to disperse the nanofillers in such polymers, however, these methods can cause undesired changes especially in the rheological properties and the physical structure of the biopolymer matrices. Recently, as a novel homogenization technique, microfluidization has been used to homogenize polymer nanocomposites to minimize these limitations. In this study, two different nanocomposite structures as chitosan/montmorillonite (CS/MMT) and chitosan/polyhedral oligomeric silsesquioxane nanocages (CS/POSS) were homogenized with microfluidization and investigated in terms of physical alterations. Furthermore, the effect of microfluidizer technique on material characteristics was compared with conventional homogenization techniques, i.e., ultrasonic bath and sonication in terms of solution, nano -(e.g., hydrodynamic size, drug encapsulation) and macroscopic material characteristics (e.g., porosity, mechanical properties, swelling and thermal degradation). It was found that the microfluidizer homogenization improves the physical characteristics in both nano and macroscale materials: Nanospheres obtained from CS/MMT composites showed enhanced stability, uniform size distribution (<100 nm, PDI: <0.2), and good encapsulation efficiency (>50%) whereas 3D porous CS/POSS scaffolds showed improved structural uniformity (i.e., homogeneous and interconnected microstructure) and enhanced thermal and mechanical properties. The obtained results indicate that the microfluidizer homogenization ensures a successful nanofiller dispersion in polymer matrices, thereby improving the biomaterial characteristics impressively compared to the sonication methods. K E Y W O R D S biomaterials, mechanical properties, microscopy, polysaccharides, porous materials Ceren Kimna and Sedef Tamburaci have equal contribution in this study.