## 1 Introduction. Pathogenic Biofilms: Characteristics and Developmental Stages  
Healthcare-associated infections (HAIs) or nosocomial infections are acquired by 4.1 million patients in the European Union each year [1], the cost of treating these infections rising to about \(\upepsilon\) 5.48 billion per year. The gravity of the situation is demonstrated by the number of deaths occurring as a direct consequence of HAIs, which is estimated to be at least 37,000 annually and by an additional number of 110,000 deaths due to other conditions that become complicated by HAIs [2]. According to estimates from the Centers for Disease Control and Prevention in the United States, biofilms are responsible for over 65% of hospital infections, a large proportion of these infections being linked to biofilm-invaded prostheses and indwelling medical devices [3]. Since modern medicine uses a plethora of implantable medical devices such as catheters, mechanical heart valves, cardiac pacemakers, coronary stents, cerebrospinal fluid shunts, joint prostheses, orthopedic fixation devices, biliary tract stents, breast implants, contact lens, dental prostheses, dental implants, and so on, colonisation of the surface of these devices by pathogenic biofilms creates a major public health problem. The management of biofilm-related infections is a critical issue since the appropriate antimicrobial therapy is often ineffective due to the increased recalcitrance of biofilm-associated bacteria. The present review aims to highlight recent nanotechnology-based strategies for biofilm-infection control. We present nanostructured coatings that through appropriate manipulation of their surface physicochemical properties are able to repel bacteria, thereby impeding the attachment step and surface biofouling (passive strategies) or to kill bacteria on direct contact (active strategies), as well as nanocoatings whose bulk chemistry was modified so that they actively release antimicrobials or other compounds that are able to hamper biofilm formation or to increase susceptibility towards antimicrobials through various mechanisms such as degrading essential chemical constituents of the biofilm matrix or disrupting signaling pathways that are vital for biofilm formation, cooperative and collective behavior, and recalcitrance development. To this purpose, we structured our review into two parts. The first part includes a short presentation of biofilm developmental stages as well as a review of new insights into molecular mechanisms of biofilm recalcitrance towards currently used antimicrobials and ends with a discussion of the bio-inspired and biomimetic passive anti-biofilm nanocoatings. The second part deals with contact-killing and active releasing nanocoatings, combined switchable active-passive strategies, as well as smart nanocoatings capable of the on-demand release of their therapeutic payload in response to triggering environmental and physiological signals. Infectious biofilms are sessile microbial aggregates exhibiting striking features, including here the expression of virulence factors that distinguish them from the same bacteria in isolation. In biofilms, bacterial cells are embedded in a sheltering extracellular polymeric matrix consisting of self-produced biomacromolecules, i.e., polysaccharides, proteins, and extracellular DNA (e-DNA) [4; 5; 6; 7]. Some extracellular polymeric substances (EPS) such as e-DNA may also be derived from the lysis of the host immune cells (polymorphonuclear leukocytes). There are two types of bacterial biofilms: ones in which the multicellular aggregates attach to an abiotic or biotic surface and others in which the multicellular aggregates are not surface-attached but rather embedded in some host-derived materials such as mucus. The switch from the free-floating motile state to the sessile biofilm mode of growth is controlled by the intracellular second messenger cyclic-diguanosine monophosphate (c-di-GMP).