Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is a glycoprotein and is derived from both hemopoietic and nonhemopoietic sources which exert immunomodulatory properties. Various theories have been proposed to explain why some wounds become chronic and non‐healing. Generalized suppression of inflammation locally or systemically may impede the body's physiological healing response by crippling the activity of reparative cells within the wound ecosystem. Thus, highlighting the importance of promoting host‐directed therapeutics with immunomodulatory properties. The temporal and spatial expression of GM‐CSF and GM‐CSF receptors in the integumentary system suggests that epithelial‐derived GM‐CSF functions in an autocrine/paracrine manner. This may positively affect wound healing physiology via local inflammatory regulation promoting macrophage survival. Although diabetes negatively affects multiple aspects of wound healing GM‐CSF activation is particularly impacted. Compared to acute/healthy wounds diabetic foot ulcers (DFU) only partially activate GM‐CSF activity. There is a deleterious chain of events associated with this unfortunate sequala. DFUs also have a high proportion of monocytes and an absence of activated macrophages which results in an impaired inflammatory response. This may potentially serve as a vital point for GM‐CSF to act as a companion diagnostic/theragnostic modality to help modulate the inflammatory response in wound healing. Correcting macrophage immune dysfunction with exogenous GM‐CSF may help restore the immune balance in the wound ecosystem and jumpstart the wound healing cascade. Thus, the recognized beneficial role of GM‐CSF in immune regulation across many studies provides a rationale for the initiation of the ongoing randomized controlled trials using GM‐CSF.

Ultrasound technology has therapeutic properties that can be harnessed to enhance topical drug delivery in a process known as phonophoresis. The literature on this method of drug delivery is currently sparse and scattered. In this review, we explore in vivo and in vitro controlled trials as well as studies detailing the mechanism of action in phonophoresis to gain a clearer picture of the treatment modality and explore its utility in chronic wound management. Upon review, we believe that phonophoresis has the potential to aid in chronic wound management, particularly against complicated bacterial biofilms. This would offer a minimally invasive wound management option for patients in the community.