Mandy Dittmer

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.

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.

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.

Biofilms are a major problem in hard-to-heal wounds. Moreover, they are composed of different species and are often tolerant to antimicrobial agents. At the same time, interspecific synergy and/or competition occurs when some bacterial species clash. For this reason, the tolerance of two dual-species wound biofilm models of Pseudomonas aeruginosa and Staphylococcus aureus or Enterococcus faecium against antimicrobials and antimicrobial dressings were analyzed quantitatively and by confocal laser scanning microscopy (CLSM). The results were compared to findings with planktonic bacteria. Octenidine-dihydrochloride/phenoxyethanol and polyhexamethylene biguanide (PHMB) irrigation solutions showed a significant, albeit delayed reduction in biofilm bacteria, while the PHMB dressing was not able to induce this effect. However, the cadexomer-iodine dressing caused a sustained reduction in and killed almost all bacteria down to 10² cfu/mL within 6 days compared to the control (10¹⁰ cfu/mL). By means of CLSM in untreated human biofilm models, it became evident that P. aeruginosa dominates over E. faecium and S. aureus. Additionally, P. aeruginosa appeared as a vast layer at the bottom of the samples, while S. aureus formed grape-like clusters. In the second model, the distribution was even clearer. Only a few E. faecium were visible, in contrast to the vast layer of P. aeruginosa. It seems that the different species avoid each other and seek their respective niches. These mixed-species biofilm models showed that efficacy and tolerance to antimicrobial substances are nearly species-independent. Their frequent application appears to be important. The bacterial wound biofilm remains a challenge in treatment and requires new, combined therapy options.