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The pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce a prolonged suboptimal inflammation in the wound microenvironment, associated with delayed healing. The composition of wound fluid (WF) adds more complexity to the subject, with proven pro-inflammatory properties and an intricate crosstalk among cytokines, chemokines, microRNAs, proteases, growth factors, and ECM components. One approach to achieve information on the mechanisms of disease progression and therapeutic response is the use of multiple high-throughput 'OMIC' modalities (genomic, proteomic, lipidomic, metabolomic assays), facilitating the discovery of potential biomarkers for wound healing, which may represent a breakthrough in this field and a major help in addressing delayed wound healing. In this review article, we aim to summarize the current progress achieved in host-microbiome crosstalk in the spectrum of CW healing and highlight future innovative strategies to boost the host immune response against infections, focusing on the interaction between pathogens and their hosts (for instance, by harnessing microorganisms like probiotics), which may serve as the prospective advancement of vaccines and treatments against infections.

Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches., Competing Interests: The authors declare no conflict of interest.

The majority of chronic infections are associated with mono- or polymicrobial biofilms, having a significant impact on the patients' quality of life and survival rates. Although the use of medical devices revolutionized health care services and significantly improved patient outcomes, it also led to complications associated with biofilms and to the emergence of multidrug resistant bacteria. Immunocompromised patients, institutionalized or hospitalized individuals, elderly people are at greater risk due to life-threatening septic complications, but immunocompetent individuals with predisposing genetic or acquired diseases can also be affected, almost any body part being able to shelter persistent biofilms. Moreover, chronic biofilm-related infections can lead to the occurrence of systemic diseases, as in the case of chronic periodontitis, linked to atherosclerosis, cardiovascular disease and diabetes. The more researchers discover, new unknown issues add up to the complexity of biofilm infections, in which microbial species establish relationships of cooperation and competition, and elaborate phenotypic differentiation into functional, adapted communities. Their interaction with the host's immune system or with therapeutic agents contributes to the complex puzzle that still misses a lot of pieces. In this comprehensive review we aimed to highlight the microbial composition, developmental stages, architecture and properties of medical biofilms, as well as the diagnostic tools used in the management of biofilm related infections. Also, we present recently acquired knowledge on the etiopathogenesis, diagnosis and treatment of four chronic diseases associated with biofilm development in tissues (chronic periodontitis, chronic lung infection in cystic fibrosis, chronic wounds) and artificial substrata (medical devices-related infections).

Difficult-to-treat infections produced by Pseudomonas aeruginosa have a long evolution with a great impact not only in regard to the patient's health, but also to his well-being, the public health and economy. Considering that not only the antimicrobial resistance, but other characteristics of these strains may be involved in the longue and difficult evolution of this infections; we evaluated the ability to produce biofilm on inert substrate through a microdilution method. We evaluated 25 strains of P. aeruginosa isolated from infections with a longue evolution. Most of the strains produced an important biofilm, especially at 48 hours, presenting an interesting architecture, suggesting the ability to persist. These findings highlight the impact of biofilm production in P. aeruginosa, and underline the importance of finding alternative therapies and a personalised approach. [ABSTRACT FROM AUTHOR]

The increasing burden of invasive biofilm-related staphylococcal infections has led to a dire need for new agents to prevent biofilm formation. Bacteriophages may hypothetically alter a biofilm through several mechanisms, including induction of depolymerizing enzymes and lysis of persistent bacteria. We have assessed the influence of commercially available bacteriophage cocktails on Staphylococcus spp. clinical strains viability and biofilm formation. We analyzed 83 staphylococcal strains from patients consecutively admitted to a Romanian infection reference center from October 2014 through May 2015; the strains were characterized by phenotypic and genetic tools for their resistance and virulence features and for their phyliation. Experiments were performed in triplicate. Methicillin-susceptible strains were significantly more susceptible to all tested phages: 1.7-fold higher susceptibility for PYO, 1.4-fold for INTESTI, 2.9-fold for PHAGYO, 2.7-fold for PHAGESTI and 3.9-fold for STAPHYLOCOCCAL; t030 strains were significantly more susceptible to PYO and INTESTI compared with t127 strains. We identified a significant decrease in biofilm formation in the presence of both low and high PYO and INTESTI concentrations (P < 0.001). In conclusion, Staphylococcus strains from Romania displayed fairly good susceptibility to commercially available bacteriophages. We have also ascertained there is phage-driven in vitro inhibition of biofilm formation, the results potentially impacting prevention of prosthetic infections. [ABSTRACT FROM AUTHOR]