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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.

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Over the last decade, chronic wounds such as venous or arterial ulcers, diabetic foot ulcers, pressure sores, and nonhealing surgical wounds were brought into the spotlight of the medical community, due to their increasing prevalence and to their significant economic burden. Vascular impairment represents the main cause of chronic ulceration, while the infection is the most frequent complication. Chronic infections persist and progress despite an adequate antimicrobial regimen and are typically caused by mono- or polymicrobial biofilms. The persistent bacterial colonization of the wound, as well as the longterm use of antibiotics predispose to the development of nosocomial infections with resistant strains, with the risk of life-threatening septic complications, especially in immunocompromised individuals. In this article, we perform a thorough literature review, in order to answer the main controversies regarding the involvement of planktonic and/or biofilm bacteria in the healing process of chronic wounds. Furthermore, we aim to analyse the utility of antimicrobial treatment in non-healing wounds, and to establish its main end-points, for the optimal benefit of the patients. [ABSTRACT FROM AUTHOR]