Monitoring the healing of combat wounds using Raman spectroscopic mapping

Abstract

Soldiers wounded in modern warfare present with extensive and complicated acute wounds, confounded by an overwhelming inflammatory response. The pathophysiology of acute wounds is unknown and timing of wound closure remains subjective. Collagen gene expression profiles are presented for 24 patients. Impaired healing wounds showed a twofold decrease in the up-regulation of COL1A1 and COL3A1 genes in the beginning of the wound healing process, compared with normal healing wounds. By the final debridement, however, collagen gene expression profiles for normal and impaired healing wounds were similar for COL1A1 and COL3A1. In addition, Raman spectroscopic maps were collected of biopsy tissue sections, from the first and last debridements of 10 wounds collected from nine patients. Tissue components obtained for the debridement biopsies were compared to elucidate whether or not a wound healed normally. Raman spectroscopy showed a loss of collagen in five patients, indicated by a negative percent difference in the 1,665/1,445 cm(-1) band area ratios. Four healed patients showed an increased or unchanged collagen content. Here, we demonstrate the potential of Raman spectroscopic analysis of wound biopsies for classification of wounds as normal or impaired healing. Raman spectroscopy has the potential to noninvasively monitor collagen deposition in the wound bed, during surgical wound debridements, to help determine the optimal time for wound closure.

Computational Approach To Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation

“…A treating clinician's decision to surgically close a wound is commonly based on subjective and somewhat arbitrary measures, such as the patient's general condition, the appearance of bones and soft tissues, and visual signs of infection or necrosis (65), which are poor indicators of the local inflammatory condition (66). This often has led to wound dehiscence and nonhealing wounds.…”

Vibrational spectroscopy: a tool being developed for the noninvasive monitoring of wound healing

“…Tissue biopsies were collected from Operation Iraqi Freedom and Operation Enduring Freedom combat-wounded soldiers at each surgical debridement during the wound-healing process. 58 Spectral maps revealed differences in the amide I∕CH 2 scissoring band area ratios that correlated with wound outcome (Fig. 3) corroborated with collagen gene expression profiles.…”

“…In impaired healing wounds, a decrease in collagen-like bands was confirmed by decreased expression of the COL1A1 and COL3A1 genes (for type I and type III collagens, respectively). 58 In addition to monitoring the wound bed itself, FTIR and Raman spectroscopy were utilized to monitor complications of wound healing, such as infection, the formation of biofilm from subsequent infection, and heterotopic ossification (HO), to which acute and chronic wounds are susceptible.…”

Raman spectroscopic analysis of combat-related heterotopic ossification development

“…These identified changes can provide objective markers that correlate with the various phases of wound healing, which can, with other clinical observations, be used to guide surgical decision-making. For instance, we previously demonstrated that changes in collagen vibrational bands can be correlated with alterations in collagen deposition associated with normal re-epithelialization of the wound bed, while perturbations of the normal collagen ratios portended impaired or delayed wound healing [14]. Prior studies have also demonstrated the ability of Raman to effectively identify and analyze bone and other mineralized tissues [17][18][19][20].…”

“…Over the past two decades, Raman spectroscopy has proven effective in assessing tissues at the molecular level with diverse clinical and diagnostic applications to include the analysis of cellular structure and the determination of tumor grade and type [8][9][10][11][12]. Accordingly, fundamental changes in the molecular environment of wounds that occur as a result of pathologic alterations can be analyzed by vibrational spectroscopy [13][14][15][16]. These identified changes can provide objective markers that correlate with the various phases of wound healing, which can, with other clinical observations, be used to guide surgical decision-making.…”