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Towards nano-based solutions for medical implants with antimicrobial properties and improved osteointegration

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Medical implants are essential in healthcare, yet their long-term success is frequently compromised by biofilm-associated infections and limited osteointegration. Prosthetic joint infections (PJIs), often caused by multidrug-resistant pathogens, such as K. pneumoniae, present a major clinical challenge due to limited treatment options and high revision surgery rates. Thus, there is a pressing need for multifunctional implant materials that simultaneously promote bone regeneration and show antimicrobial properties. This thesis explored the use of silver nanostars (AgNS) and 1-hydroxyphenazine (HP), a bioactive compound, as potential candidates for nano-based implant coatings. AgNS were synthesized and characterized using spectroscopic and microscopy techniques, confirming their star-shaped morphology, stability, and high surface-to-volume ratio. Their antimicrobial activity against K. pneumoniae was determined to be highly efficient, with an estimated minimum inhibitory concentration (MIC) of 1.0 nM, markedly lower that conventional silver nanoparticles. HP showed a MIC below 250 μM and, when combined with AgNS, a synergistic effect was observed, further enhancing bacterial inhibition. Biocompatibility and osteogenic potential were assessed using the MG-63 osteoblast-like cell line. Titanium (Ti) discs, uncoated and fibronectin-coated, supported osteoblast viability and differentiation capacity. Osteogenic induction, confirmed via extracellular protein secretion, alkaline phosphatase activity, and morphological changes, was further validated by BMP-2 supplementation as a proof of concept. Importantly, AgNS and HP were successfully conjugated and used as a coating on Ti discs, with microscopy analyses revealing effective surface coverage and nanostructuring, suggesting potential for improved osteointegration. Overall, the work hereby described demonstrates the potential of HP-AgNS nanosystems as novel multifunctional coatings for biomedical applications, specifically for medical implants. By combining effective antimicrobial activity with osteointegration, these nano-based solutions may contribute to increasing implant success rates.

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Tese de mestrado, Biologia Molecular e Genética , 2025, Universidade de Lisboa, Faculdade de Ciências

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Silver nanostars 1-hydroxyphenazine antimicrobial coatings osteogenesis nanomedicine

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