Sr2+ hydroxyapatite and polylactic acid nanoparticles doped antimicrobial bioactive chitosan-based coating for medical device osteointegration

Bioactive coatings that combine antibacterial and pro-osteogenic components are gaining increasing attention for their ability to prevent bacterial adhesion and surface colonization while promoting integration with host tissues. This study focused on designing and developing antimicrobial nanoparticle (NP)-loaded chitosan films doped with Sr2+-enriched hydroxyapatite (SrHA) as bioactive coatings for orthopaedic medical devices. At this purpose, blank and thymol-loaded PLA nanoparticles were produced by microfluidics techniques, and the impact of the different process parameters was evaluated. The results show that nanosized particles ranging from 150 to 250 nm were produced across all PLA concentrations tested and thymol was delivered into the nanoparticles with a drug loading (DL%) of 5.8% (+/- 0.7 SD). Moreover, the SrHA was synthetized and characterized comparing it's physical-chemical properties with that of a commercial HA. In detail, the results confirm the incorporation of Sr2+ within the apatite structure with a weight ratio % around the 30%. Then, the crystalline pattern of SrHA was also investigated resulting in a crystalline structure with higher amorphous domains than those of the HA structure highlighted by the broadened peaks to the XRPD pattern due to the substitution of Ca2+ with Sr2+ characterized by larger atomic radius. Chitosan films incorporating thymol-loaded NPs and SrHA were produced using solvent casting technique and characterized through a multidisciplinary approach. The mechanical properties, along with the favourable morphology and topography of the coatings, appeared to enhance the biological response. The resulting systems supported mesenchymal stem cell proliferation and promoted the expression of genes related to osteoinduction while also exhibiting antimicrobial activity against both Grampositive and Gram-negative bacterial strains. Preclinical evaluations provided sufficient evidence of efficacy and safety, paving the way for their use as pro-osteogenic and antimicrobial coatings for orthopaedic devices as hybrid multifunctional coatings providing antimicrobial protection and pro-osteogenic stimulation offering a novel route to address two major clinical challenges such as early-stage bacterial contamination and insufficient osteointegration.