Hard-to-heal wounds: A new biofilm treatment with a novel desiccant

Biofilms are slow-growing communities of multiple strains of bacteria that resist both innate immune mechanisms as well as antibiotics [1] [16] [17]. They also contain extracellular DNA (bacterial or host origin), polysaccharides, and proteins that form dense matrix is resistant to the host’s innate immune response [18] [19].


Introduction
Biofilms are believed to occur in 60-100% of chronic wounds [2] [5]. The World Union of Wound Healing Societies released a position statement that they believe clinicians should assume that all chronic wounds that have failed to heal under standard of care contain a biofilm [3] [20].
Biofilms are a self-feeding barrier:  With resistance to host's innate immune response  With resistance to antibiotics due to slow growth rate o The mechanism for antibiotic function happens during replication, therefore low replication, low antibiotic activity.  Secrete glycolipids that disrupt signaling as well as proteolytic enzymes that attack ECM proteins Chronic skin wounds represent a major health problem and financial burden [21].

Biofilm
There are many factors in biofilms that contribute to inhibition of wound healing. Data suggest that chronic wounds are trapped in the acute inflammatory phase of healing, which amplifies over time [8]. Dynamic Reciprocity (DR) is out of balance [9] [28]. DR is an ongoing, bidirectional interaction between cells and their surrounding microenvironment (including ECM), it plays critical role in biochemical, biophysical and cellular responses that regulate tissue regenerative responses. DR between cells and Extracellular matrix (ECM) [10].
Cells synthesize ECM components, and degrade and remodel ECM, the latter events occurring through the production and regulation of matrix metalloproteases (MMPs) and other enzymes.
The ECM regulates cellular tension and polarity, differentiation, migration, proliferation, and survival.
The composition of the ECM varies by tissue and by state of the tissue (i.e., intact adult tissue, healing wound, etc.) Due to their continued persistence, biofilm infections cause more damage and greater inflammatory responses than the corresponding infections caused by planktonic bacteria [6] [7] [22] [23].
The biofilm matrix, composed of proteins, DNA and sugars, is called Extracellular Polymer Substance, or EPS1-3 The biofilm is difficult to eradicate because it is resistant to antimicrobial therapies [24] [25]. and to the host's immune system [2] [3].
To effectively eradicate the biofilm and promote healing, an antimicrobial must be able to penetrate the EPS and attack the bacteria inside with a prolonged action that prevents the biofilm from reforming [26] [27]. P-toluensulfonic acid is used for the topical/local treatment of skin areas at high risk of bacterial development thanks to its ability to remove bacterial biofilm with a physical mechanism of action dependent on the dehydrating nature of the product and independent of the bacterial species present.
Wound Bed Preparation was performed solely as surgical debridment [4].
Dessicating agent was applied and distributed with a gloved finger on the wound bed and approximately 1 cm margin of surrounding healthy skin and had remained on the wound bed for 10-15 seconds. The wound has been rinsed with wet (saline) sterile gauze and medicated as usual.
This procedure has been repeated at 1 week interval until the wound bed had progressed up to 100% granulation, wound healing to spontaneous reepithelization or skin graft or ADM.

Conclusion
Overall, p-toluensulfonic acid reports a remarkable anti-biofilm effect and promote healing. Dissecating agent treatment appears to restart the healing process of chronic ulcers.

Acknowledgments
The Authors acknowledge the p-toluensulfonic acid Italian producer for providing the material for the cases described.

Disclosure of conflict of interest
The Authors have no actual or potential conflict of interest in relation to this paper.

Statement of informed consent
Informed consent was obtained from all individual included in cases study.