How does biofilm affect wound healing?

In wound healing, the intricate relationship between cellular processes orchestrates the healing journey, but there is a hidden enemy – biofilm. Often overlooked, yet a common factor in hard-to-heal wounds, biofilm presents a formidable challenge for healthcare professionals as they strive to accelerate wound healing and mitigate complications. So how does biofilm affect wound healing?

Understanding biofilm: the invisible intruder

At its core, biofilm is a complex matrix of microorganisms encased within a protective exopolysaccharide matrix¹, or EPS. These microorganisms, which can include one or more types of bacteria, fungi and other pathogens, adhere to surfaces and form a structured community, often embedded within wounds².

Unlike their planktonic counterparts, microorganisms within biofilms exhibit heightened resistance to antimicrobial agents and host immune defences². The composition of the matrix, which incorporates various polymers like polysaccharides, proteins, and nucleic acid released from cells, protects the biofilm’s bacteria from environmental stress such as dehydration, UV exposure, salinity, metal toxicity, antimicrobials and phagocytosis³. This resilience poses a significant barrier to wound healing, as biofilm-mediated infections frequently persist despite conventional treatment approaches.

The interplay with wound healing

Biofilm's impact on wound healing is multifaceted, with detrimental effects at various stages of the repair process:

Delayed healing

In normal wound healing, the inflammatory stage lasts around 48 hours⁴. However, biofilm impedes the orderly progression of wound healing by causing a chronic inflammatory state⁵. Persistent inflammation, fuelled by the release of pro-inflammatory cytokines and toxic byproducts from biofilm communities, disrupts the delicate balance between tissue regeneration and degradation. As a result, the proliferation and remodelling phases of wound healing are hindered, leading to delayed closure and compromised tissue integrity⁶.

Impaired angiogenesis

Angiogenesis, the formation of new blood vessels needed to deliver oxygen and nutrients to the wound bed during wound healing, is impaired by biofilm-induced hypoxia and inflammation⁷. The disturbance to the release of substances that help blood vessels grow, such as vascular endothelial growth factor (VEGF), compromises vascular network formation, impeding tissues’ blood flow and exacerbating ischemic conditions within the wound microenvironment.

Dysfunctional extracellular matrix (ECM) remodelling

Biofilm-derived enzymes, particularly proteases (also called peptidases), degrade the extracellular matrix (ECM), a structural scaffold critical for tissue repair⁸. This deviant ECM remodelling disrupts cell-matrix interactions, impairs cell migration, and compromises the formation of new connective tissue components. Consequently, wound closure is hampered, and the risk of chronicity increases.

Immune Dysregulation

Biofilm-mediated immune evasion mechanisms impact the host immune response, perpetuating a state of persistent infection that prevents wound healing. This dysregulation is characterised by impaired phagocytosis, diminished antimicrobial peptide production and skewed cytokine profiles, fostering an immunosuppressive microenvironment that assists microbial proliferation⁹.

Navigating the complexities

In the intricate landscape of wound healing, biofilm emerges as a persistent opponent, challenging healthcare professionals to adopt innovative strategies and collaborative approaches in its management. However, by demystifying the intricate interplay between biofilm and wound healing processes, clinicians can devise tailored interventions and adopt collaborative interdisciplinary approaches to advance wound care and improve patient outcomes, such as Wound Hygiene.

References

[1] Sharma S, Mohler J, Mahajan SD, Schwartz SA, Bruggemann L, Aalinkeel R. Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment. Microorganisms [Internet]. 2023 Jun 1;11(6):1614. Available from: https://www.mdpi.com/2076-2607/11/6/1614

[2] Schulze A, Mitterer F, Pombo JP et al. Biofilms by bacterial human pathogens: Clinical relevance - development, composition and regulation - therapeutical strategies. Microb Cell. 2021;8(2):28-56. Published 2021 Feb 1. doi:10.15698/mic2021.02.741

[3] González JF, Hahn MM, Gunn JS. Chronic biofilm-based infections: skewing of the immune response. Pathog Dis. 2018;76(3):fty023. doi:10.1093/femspd/fty023

[4] Trøstrup H, Laulund ASB, Moser C. Insights into Host-Pathogen Interactions in Biofilm-Infected Wounds Reveal Possibilities for New Treatment Strategies. Antibiotics (Basel). 2020;9(7):396. Published 2020 Jul 10. doi:10.3390/antibiotics9070396

[5] Mendoza RA et al. ‘The Impact of Biofilm Formation on Wound Healing’. Wound Healing - Current Perspectives, IntechOpen, May 10 2019. doi:10.5772/intechopen.85020.

[6] Zhao G, Usui ML, Lippman SI et al. Biofilms and Inflammation in Chronic Wounds. Adv Wound Care (New Rochelle). 2013;2(7):389-399. doi:10.1089/wound.2012.0381

[7] Hu D, Zou L, Yu W et al. Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy. Adv Sci (Weinh). 2020;7(12):2000398. Published 2020 May 14. doi:10.1002/advs.202000398

[8] Ramírez-Larrota JS, Eckhard U. An Introduction to Bacterial Biofilms and Their Proteases, and Their Roles in Host Infection and Immune Evasion. Biomolecules. 2022;12(2):306. Published 2022 Feb 14. doi:10.3390/biom12020306

[9] Roy R, Tiwari M, Donelli G et al. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence. 2018;9(1):522-554. doi: 10.1080/21505594.2017.1313372