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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.

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).

Chronic wounds encompass a myriad of lesions, including venous and arterial leg ulcers, diabetic foot ulcers (DFUs), pressure ulcers, non-healing surgical wounds and others. Despite the etiological differences, chronic wounds share several features at a molecular level. The wound bed is a convenient environment for microbial adherence, colonization and infection, with the initiation of a complex host–microbiome interplay. Chronic wound infections with mono- or poly-microbial biofilms are frequent and their management is challenging due to tolerance and resistance to antimicrobial therapy (systemic antibiotic or antifungal therapy or antiseptic topicals) and to the host's immune defense mechanisms. The ideal dressing should maintain moisture, allow water and gas permeability, absorb wound exudates, protect against bacteria and other infectious agents, be biocompatible, be non-allergenic, be non-toxic and biodegradable, be easy to use and remove and, last but not least, it should be cost-efficient. Although many wound dressings possess intrinsic antimicrobial properties acting as a barrier to pathogen invasion, adding anti-infectious targeted agents to the wound dressing may increase their efficiency. Antimicrobial biomaterials may represent a potential substitute for systemic treatment of chronic wound infections. In this review, we aim to describe the available types of antimicrobial biomaterials for chronic wound care and discuss the host response and the spectrum of pathophysiologic changes resulting from the contact between biomaterials and host tissues. [ABSTRACT FROM AUTHOR]