Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration



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pharmaceutics-12-00735
Figure 3. Schematic representation of Tissue (T), Infection (I), Moisture (M) and Epithelial (E) (TIME) 
concept. 
3.1.1. Tissue (T): Debridement Procedure 
Over the past decade, new therapies for wound debridement have been developed, such as 
low-frequency ultrasounds, hydro-surgery devices, larvae and enzyme agents. It is widely 
recognized that devitalized tissue removal is a fundamental process for tissue repair [39]. 
Debridement is optimal for preparing the wound bed, but in some cases is not recommended (i.e., in 
immunosuppressed patients). Once all injury assessment factors have been revised, and wound 
debridement has been decided as an appropriate option, the most appropriate debridement method 
should be selected [40], taking in consideration the amount of exudate produced by the wound. The 
most common debridement types are as follows. Autolytic: the body uses endogenous enzymes and 
moisture gradients to remove devitalized and necrotic tissue. This is a long process, more suitable 
for minor injuries. Wound care products such as hydrogels, films, honey and hydrocolloids can be 
used to support this natural process and allow wound healing in a humid environment [39]. 
Surgical: surgical removal allows us to identify the entire condition of the wound. Sterile 
instruments are used to remove devitalized or necrotic tissues; often, this procedure also removes 
some vital tissue. Surgical debridement is fast, safe, minimizes the risk of infection and chronic 
wound complications [41]. Mechanical: this is an effective and economical method of debridement. 
The disadvantages of this method are the lack of selectivity and pain. It can be applied through 
hydrotherapy, using water jets to wash residues from the wound surface. Another mechanical 
debridement method is wet–dry therapy, where a wet gauze is applied to a wound and then left to 
dry; once dried, the gauze that bound the necrotic or devitalized tissue is removed from the wound 
bed [42]. Biological: the application of sterile larvae-secreting enzymes, able to liquefy dead tissue
the liquid-containing bacteria is then ingested and neutralized by larval bowels. In addition, there is 
an increase in wound bed growth rates and advantageous changes to skin pH values. This 
procedure provides a safe and selective debridement method; however, it is poorly accepted by 
patients and doctors [43]. Enzymatic: this procedure involves the application of enzymes into the 

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