The wound microbiome refers to the specific community of microbes, including bacteria, fungi, and other microorganisms, that are present in and around a wound. This microbiome plays a crucial role in wound healing, as it includes both healing-promoting and pathogenic microbes. The balance between these microbes significantly influences the healing process; a balanced microbial colonization can support wound healing and prevent infections, while an overgrowth of pathogenic microbes can lead to delayed healing processes and complications. The composition of the wound microbiome can vary depending on the type of wound, cause, genetic predisposition, and (social) environment. In this scope review, the complex interactions in the wound microbiome will be highlighted and the importance of non-pathogenic microbes for wound healing will be discussed. In addition, possible therapeutic approaches to restore a healthy microbiome and prevent infections will be addressed. A deeper understanding of these dynamics could open up new perspectives for the treatment of wounds and the development of strategies to combat wound infections.

Background: Chronic wounds are frequently associated with biofilms, in which not only bacterial but also fungal pathogens can impair wound healing. Among the most relevant opportunistic pathogens is Staphylococcus aureus; together with Candida albicans, both are part of the human skin microbiome but can also colonize chronic wounds. Interkingdom biofilms formed by these microorganisms have been shown to exacerbate the course of diseases compared to infections caused by either species alone. Methods: To address the limited number of studies examining fungal–bacterial interactions in wound environments, leucocyte-rich human plasma biofilm models (lhBIOMs) inoculated with S. aureus and C. albicans were prepared. The efficacy of the commonly used clinical antiseptics octenidine dihydrochloride/phenoxyethanol (OCT/PE) and polyhexamethylene biguanide (PHMB) was examined using the quantitative suspension method (QSM). In addition, spatial distribution and morphology of the microorganisms within this biofilm model were analyzed by confocal laser scanning microscopy (CLSM). Results: In this study, the presence of S. aureus triggered an increase in the formation of filamentation of C. albicans in contrast to the single-species biofilm. In addition, treatment with the tested antimicrobial agents was effective against C. albicans after repetitive applications and showed a clear reduction against S. aureus. Furthermore, the quantitative analysis of the co-culture revealed increased growth of S. aureus in the control culture compared to the single-species model. Conclusions: These findings highlight the pathogenic relevance of interkingdom biofilms in chronic wounds and emphasize the importance of effective species-independent antimicrobial treatment strategies.

Wound odor is a common symptom in patients with chronic wounds. Malodorous wounds can result in embarrassment, anxiety, and, therefore, in social isolation of the patient. Current treatment options are limited and focused on masking the odor. Current approaches to wound odor management have notable limitations and fail to adequately address existing therapeutic needs. Wound odor is multifactorial, with a major contribution from volatile organic compounds (VOCs) emitted by microorganisms and necrotic tissue. Several VOCs have been identified as key drivers of malodor, such as short-chain fatty acids, dimethyl-trisulfide, specific alcohols, ketones, and aldehydes. These compounds are detected by the human olfactory system, including olfactory receptors (ORs) expressed on olfactory sensory neurons (OSNs). The human olfactory system comprises more than 400 ORs, which enable the detection of a vast array of odorants, however only a small fraction of these receptors has been deorphanized. This systematic review will evaluate therapeutic clinical strategies addressing malodor and compile current knowledge on VOCs that cause wound odor and the ORs associated with their detection. It summarizes the existing evidence on deorphanized ORs that detect these VOCs in malodorous wounds and outlines experimental mechanisms of deorphanization. Identifying wound-odor-associated VOCs and their corresponding ORs provides a framework for novel therapeutic strategies, such as antagonizing the OR to suppress odor perception. This may directly improve the quality of life of patients with chronic malodorous wounds, particularly in malignant wounds and palliative care.

Biodegradable biomaterials are promising candidates for regenerative wound care, yet their performance under infection-driven conditions remains poorly understood. This study evaluated the regenerative efficacy and structural persistence of a silk fibroin membrane and electrospun nonwoven matrix using a human ex vivo full-thickness skin wound model under non-infected and bacterially infected conditions. Complementary in vitro degradation assays assessed matrix durability following exposure to Staphylococcus aureus, Pseudomonas aeruginosa, bacterial culture supernatants and clinically relevant antiseptic solutions. In non-infected wound conditions, both matrices enhanced wound regeneration, resulting in increased re-epithelialization and proliferative activity compared with untreated controls; membrane-treated wounds achieved approximately 95% re-epithelialization after 15 days compared with approximately 20% in untreated controls, indicating accelerated wound closure, whereas nonwoven matrices supported sustained cellular proliferation over time. In contrast, bacterial infection was associated with almost complete absence of re-epithelialization and proliferative activity irrespective of matrix architecture. Matrix persistence was pathogen-dependent. While S. aureus induced moderate degradation, P. aeruginosa caused pronounced structural deterioration in ex vivo and in vitro models. Exposure to P. aeruginosa culture supernatants produced similar effects. These findings demonstrate that regenerative efficacy and material persistence are distinct biomaterial properties that are strongly influenced by the wound microbiological environment and are profoundly compromised under conditions of high bacterial burden.