Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds

Gregory T. Christopherson, Jaira F. de Vasconcellos, John C. Dunn, Daniel W. Griffin, Patrick E. Jones, Leon J. Nesti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


BACKGROUND:: The development of post-traumatic heterotopic ossification (HO) is a common, undesirable sequela in patients with high-energy (war-related) extremity injuries. While inflammatory and osteoinductive signaling pathways are known to be involved in the development and progression of post-traumatic HO, features of the structural microenvironment within which the ectopic bone begins to form remain poorly understood. Thus, increasing our knowledge of molecular and structural changes within the healing wound may help elucidate the pathogenesis of post-traumatic HO and aid in the development of specific treatment and/or prevention strategies. METHODS:: In this study, we performed high-resolution microscopy and biochemical analysis of tissues obtained from traumatic war wounds to characterize changes in the structural microenvironment. In addition, using an electrospinning approach, we modeled this microenvironment to reconstitute a three-dimensional type I collagen scaffold with non-woven, randomly oriented nanofibers where we evaluated the performance of primary mesenchymal progenitor cells. RESULTS:: We found that traumatic war wounds are characterized by a disorganized, densely fibrotic collagen I matrix that influences progenitor cells adhesion, proliferation and osteogenic differentiation potential. CONCLUSION:: Altogether, these results suggest that the structural microenvironment present in traumatic war wounds has the potential to contribute to the development of post-traumatic HO. Our findings may support novel treatment strategies directed towards modifying the structural microenvironment after traumatic injury.

Original languageEnglish
Pages (from-to)963-973
Number of pages11
JournalTissue Engineering and Regenerative Medicine
Issue number6
StatePublished - Dec 2021
Externally publishedYes


  • Fibrosis
  • Heterotopic ossification
  • Stem cells
  • Trauma
  • War wounds


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