2. Academic Validation
  3. Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds

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

  • Tissue Eng Regen Med. 2021 Dec;18(6):963-973. doi: 10.1007/s13770-021-00355-y.
Gregory T Christopherson  # 1 2,  Jaira F de Vasconcellos  # 2 3 4,  John C Dunn 2,  Daniel W Griffin 5,  Patrick E Jones 5,  Leon J Nesti 6 7
Affiliations

Affiliations

  • 1 Orthopaedic Research Group, National Institute of Arthritis, Musculoskeletal and Skin Disease, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
  • 2 Clinical and Experimental Orthopaedics, Department of Surgery, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
  • 3 Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
  • 4 Department of Biology, James Madison University, 951 Carrier Drive, Harrisonburg, VA, 22807, USA.
  • 5 Department of Orthopaedic Surgery, Walter Reed National Military Medical Center, 104 Wood Rd, Bethesda, MD, 20814, USA.
  • 6 Clinical and Experimental Orthopaedics, Department of Surgery, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. leon.nesti@usuhs.edu.
  • 7 Department of Orthopaedic Surgery, Walter Reed National Military Medical Center, 104 Wood Rd, Bethesda, MD, 20814, USA. leon.nesti@usuhs.edu.
  • # Contributed equally.
PMID: 34363599 DOI: 10.1007/s13770-021-00355-y
Abstract

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.

Keywords

Fibrosis; Heterotopic ossification; Stem cells; Trauma; War wounds.

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