The role of the inflammatory response in mediating functional recovery following composite tissue injuries

Naveena B. Janakiram, Michael S. Valerio, Stephen M. Goldman, Christopher L. Dearth*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and adaptive immune responses. Unlike normal wound healing, in CTI, disruptions occur in innate immune responses, altering neutrophil functions, macrophage activation and polarization, further impacting the functions of T regulatory cells. Additionally, the biological underpinnings of these unfavorable wound healing conditions are multifactorial, including various processes, such as: ischemia, hypoxia, low nutrient levels, and altered cell metabolic pathways, among others, all of which are thought to trigger anergy in immune cells and destabilize adaptive immune responses. As a result, impaired wound healing is common in CTI. Herein, we review the altered innate and adaptive immune cells and their metabolic status and responses following CTI, and discuss the role a multi-pronged immunomodulatory approach may play in facilitating improved outcomes for afflicted patients.

Original languageEnglish
Article number13552
JournalInternational Journal of Molecular Sciences
Issue number24
StatePublished - 1 Dec 2021
Externally publishedYes


  • Composite musculoskeletal trauma
  • Immunomodulation
  • Inflammation
  • Military medicine
  • Tissue regeneration
  • Wound healing


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