Excursion: General wound treatment:
Wound healing consists of three consecutive phases which also partly overlap at times. The cleansing phase which consists of exudation, hemostasis and inflammation is followed by the granulation phase. In this phase, the formation of tissue and blood vessels takes place. During the following epithelisation phase, the wound healing is completed, scar tissue is formed and the epithelisation of the wound takes place. Depending on the size and type of the wound, this whole process is completed after roughly 14 to 21 days.
With chronic wounds, this temporal sequence is disrupted and in some cases noticeably prolonged because the cause is either unknown or cannot be/ is not adequately treated. The insufficient or non-existant causal therapy then leads to impaired wound healing. This way, with chronic wounds this process can last for months or even years before the wound eventually completely heals itself.
Hemostasis follows a specific pattern: The narrowing of blood vessels leads to a reduced blood flow. Then, blood platelets (thrombocytes) adhere to collagen fibers. More and more thrombocytes arrive to form a clog together.
Exudation/cleansing phase
During the cleansing phase (also called exudation and inflammation phase), the cells and hormones of the immune system are strongly involved in the killing off of intrusive germs and viruses as wall as in the stimulation of the healing process. The increasingly produced macrophages play an important role in this process. They cleanse the wound and produce growth factors that are essential for the subsequent healing of the wound.
Especially the neutrophil granulocytes are able to dissolve died-off tissue and to phagocytose bacteria. The majority of leukocytes disintegrate which leads to a release of hydrolytic enzymes which for their part dissolve cell debris. The immigrating monocytes then phagocytose this cell debris. Macrophages play a central role in this process: They cause the cleansing of the wound via phagocytosis. Moreover, they produce growth factors which stimulate the subsequent phases of wound healing. They also stimulate the multiplication of fibroplasts and initiate vascularisation. This activity, however, is only possible within moist wound conditions. With chronic wounds, this phase is often significantly prolonged because reactions to bacterial infection slow down wound healing.
Granulation phase
The granulation phase reaches its maximum within 72 hours and normally starts after roughly 24 hours. Fibroblasts produce extrazellular matrix components such as collagen and hyaluronan. Hyaluronan can absorb up to 3000 times of its own weight in moisture. The matrix that is formed mostly thanks to hyaluronan is very stable and can nevertheless easily be extended. This way, it is easy for fibroplasts and keratiocytes to migrate into the matrix which leads to the formation of new tissue and the filling of the wound.
Epithelisation phase
The Epithelisation phase is initiated by the migration of keratinocytes. Collagen fibers are increasingly synthesized, form a connection and become scar tissue. The application of hyaluronan during this process leads to a slight decrease in the production of collagen fibers and therefore reduces the formation of scar tissue. Epidermal cells, in most cases, start to unevenly spread, starting from the margin of the scar across the wound surface. It is, however, also possible that islands of epithelial tissue spread from within particular areals of the wound. In this case, a migration is also possible which consequently leads to the complete closure of the wound.
Entry points for cold plasma, ECA, hyaluronan and micro-silver:
Cleansing phase (inflammation & exudation)
Granulation phase
Literature references:
Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol 2009; 9: 259–70.
Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010; 141: 39–51.
Hoppe HD, Lobmann R: Medizin & Praxis 2008; Spezial Mai, Chronische Wunden: 77–82
Willenborg, Emig: Journal of German Society of Cermatology 2013: Makrophagen – Effektorzellen in der Wundheilung
Daeschlein, G., et al, Plasma Kurrier 1/2014: Stellenwert moderner physikalischer Behandlungsverfahren bei infizierten und kolonisierten Wunden in der Dermatologie
Kraemer et al; Skin Pharmacol Physiol 2018;31:28–58 “Guidline for antiseptic wound treatment”
Daeschlein et al, Plasma Kurrier 1/2014: In vitro Susceptibility of Important Skin and Wound Pathogens Against Low Temperature Atmospheric Pressure Plasma Jet (APPJ) and Dielectric Barrier Discharge Plasma (DBD)
Weltman, Woedtke; Plasma Physics and Controlled Fusion 59(1):014031 · January 2017: Plasma medicine - Current state of research and medical application
Kraemer et al; Skin Pharmacol Physiol 2018;31:28–58 “Guidline for antiseptic wound treatment”
Daeschlein, G., et al, Plasma Kurrier 1/2014: Stellenwert moderner physikalischer Behandlungsverfahren bei infizierten und kolonisierten Wunden in der Dermatologie
