The emergence of resistant pathogens is a burden on mankind and threatens the existence of our species. Natural and plant-derived antimicrobial agents need to be developed in the race against antibiotic resistance. Nanotechnology is a promising approach with a variety of products. Biosynthesized silver nanoparticles (AgNP) have good antimicrobial activity. We prepared AgNPs with trans-cinnamic acid (TCA) and povidone-iodine (PI) with increased antimicrobial activity. We synthesized also AgNPs with natural cinnamon bark extract (Cinn) in combination with PI and coated biodegradable Polyglycolic Acid (PGA) sutures with the new materials separately. These compounds (TCA-AgNP, TCA-AgNP-PI, Cinn-AgNP, and Cinn-AgNP-PI) and their dip-coated PGA sutures were tested against 10 reference strains of microorganisms and five antibiotics by zone inhibition with disc-and agar-well-diffusion methods. The new compounds TCA-AgNP-PI and Cinn-AgNP-PI are broad spectrum microbicidal agents and therefore potential coating materials for sutures to prevent Surgical Site Infections (SSI). TCA-AgNP-PI inhibits the studied pathogens stronger than Cinn-AgNP-PI in-vitro and on coated sutures. Dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier Transform infrared spectroscopy (FT-IR), Raman, X-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) confirmed the composition of TCA-AgNP-PI and Cinn-AgNP-PI. Smart solutions involving hybrid materials based on synergistic antimicrobial action have promising future perspectives to combat resistant microorganisms.Pharmaceutics 2020, 12, 361 2 of 36 20,000 related deaths in the United States in 2017 only and remains to be one of the important infection-associated mortality reasons [11,12]. The formation of biofilms on biotic and abiotic surfaces [13] paved the way for biofilm antibiotic tolerance as another major health threat [14,15]. This additional problem hampers the treatment of infections, most often gives rise to chronic infections, in the worst case to therapeutic failure, severe morbidity, and mortality [4]. More than 80% of microbial infections are caused by microbial biofilm formation and pose a severe health risk because treatment with antibiotics remains ineffective [16]. The incidence of chronic wound infections is increasing globally to alarming levels [17]. Chronic wounds are marked by high bacterial colonization and infection rates, which can be treated only by novel therapeutic approaches other than the use of conventional antibiotics [18,19]. Chronic wound tissues can contain microbiomes of complex communities with coexisting fungal and bacterial colonies of different strains within biofilms [20]. According to this inter-kingdom model, fungi like Candida albicans can offer structures for other bacteria (S. aureus, P. aeruginosa, Streptococcus spp., E. faecalis, E. coli, and Acinetobacter baumannii etc.) to attach, form intricate biofilms, and increase the resistance against any ...