Surgery is the definitive treatment for
burn patients who sustain full-thickness
burn injuries. Visual assessment of
burn depth is made by the clinician early after injury but is accurate only up to 70% of the time among experienced surgeons.
Collagen undergoes denaturation as a result of thermal injury; however, the association of
collagen denaturation and cellular death in response to thermal injury is unknown. While gene expression assays and histologic staining allow for ex vivo identification of
collagen changes, these methods do not provide spatial or integrity information in vivo. Thermal effects on
collagen and the role of
collagen in
wound repair have been understudied in human
burn models due to a lack of methods to visualize both intact and denatured
collagen. Hence, there is a critical need for a clinically applicable method to discriminate between damaged and intact
collagen fibers in tissues. We present two complementary candidate methods for visualization of
collagen structure in three dimensions. Second harmonic generation imaging offers a label-free, high-resolution method to identify intact
collagen. Simultaneously, a fluorophore-tagged
collagen-mimetic
peptide can detect damaged
collagen. Together, these methods enable the characterization of
collagen damage in human skin biopsies from
burn patients, as well as ex vivo thermally injured human skin samples. These combined methods could enhance the understanding of the role of
collagen in human wound healing after thermal injury and potentially assist in clinical decision-making.