TABLE 2.

Representative findings resulting from studies focusing on chronic wound pathophysiology using biomaterial other than tissue specimens (blood, wound fluid, swabs)

Discovery	Type of analysis	Ref.
Genetic variation in NOS1AP gene may diminish circulating stem cell response and is associated with impaired healing of DFU (n = 47)	Genomics	[87]
Feasibility of modern spectroscopy utilized to associate metabolic products and bacterial infection in chronic wound exudate (n = 20)	Metabolomics microbiology,	[105]
Bacteria isolated from chronic VLUs can secrete proteases that degrade extracellular matrix important for wound healing (n = 6)	Microbiology, enzyme activity	[137]
Microbial instability and diversity were associated with healing DFU (n = 100)	Microbiome analyses	[56]
Specific fungal species and polymicrobial bacteria-fungus biofilms correlate with non-healing outcomes in DFUs (n = 100)	Mycobiome sequencing	[97]
Unique thrombin-derived peptides identified in non-healing wounds infected with S. aureus and Pseudomonas aeruginosa	Proteomics	[93]
The biological microenvironment of chronic wounds exhibits diminished angiogenesis, increased inflammation and higher cell death compared with acute healing process (n = 10)	Proteomics	[102]
Elevated levels of matrix metalloproteinase (MMP) activity are associated with healing impairment in chronic ulcers (n-28)[78] (n = 56)[85] (n = 25)[104] (n = 290)[108]	Proteomics, enzyme activity	[78,85,104,108]
Chronic wound fluid has high levels of matrix metalloproteinases and is capable of fibronectin degradation (n = 10)	Proteomics	[138]
Environment of non-healing ulcers has high levels of activated MMPs which contribute to poor wound healing. (n = 6)[74] (n = 56)[80]	Enzyme activity, proteomics	[74,80]

n, number of human subjects.

Major type of analyses utilized in the study is outlined.