TY - JOUR
T1 - Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds
AU - Christopherson, Gregory T.
AU - de Vasconcellos, Jaira F.
AU - Dunn, John C.
AU - Griffin, Daniel W.
AU - Jones, Patrick E.
AU - Nesti, Leon J.
N1 - Funding Information:
We thank Dr. Richard Leapman and his laboratory at the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, for his generous support in providing scanning electron microscopy evaluation for the tissues used in this study. We thank the contribution of patients and their families, physicians and nurses in providing primary samples for this study.
Funding Information:
This work was supported by the Military Amputee Research Program at Walter Reed Army Medical Center (P05-A011), the Comprehensive Neurosciences Program (CNP-2008-CR01), the Defense Medical Research and Development Program (D10_1_AR_J5_920), the Congressionally Directed Medical Research Program (W81XWH-13-2-0083), the NIH Intramural Research Program (Z01 AR41131), and the USAMRAA BAA (W81XWH-17-2-0009).
Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Fibrosis
KW - Heterotopic ossification
KW - Stem cells
KW - Trauma
KW - War wounds
UR - http://www.scopus.com/inward/record.url?scp=85112654455&partnerID=8YFLogxK
U2 - 10.1007/s13770-021-00355-y
DO - 10.1007/s13770-021-00355-y
M3 - Article
C2 - 34363599
AN - SCOPUS:85112654455
SN - 1738-2696
VL - 18
SP - 963
EP - 973
JO - Tissue Engineering and Regenerative Medicine
JF - Tissue Engineering and Regenerative Medicine
IS - 6
ER -