Journal article
Burn Injury Enhances Bone Formation in Heterotopic Ossification Model
Annals of surgery, Vol.259(5), pp.993-998
05/01/2014
DOI: 10.1097/SLA.0b013e318291da85
PMCID: PMC4498401
PMID: 23673767
Abstract
Objective: To demonstrate the pro-osteogenic effect of burn injury on heterotopic bone formation using a novel burn ossicle in vivo model.
Background: Heterotopic ossification (HO), or the abnormal formation of bone in soft tissue, is a troubling sequela of burn and trauma injuries. The exact mechanism by which burn injury influences bone formation is unknown. The aim of this study was to develop a mouse model to study the effect of burn injury on heterotopic bone formation. We hypothesized that burn injury would enhance early vascularization and subsequent bone formation of subcutaneously implanted mesenchymal stem cells.
Methods: Mouse adipose-derived stem cells were harvested from C57/BL6 mice, transfected with a BMP-2 adenovirus, seeded on collagen scaffolds (ossicles), and implanted subcutaneously in the flank region of 8 adult mice. Burn and sham groups were created with exposure of 30% surface area on the dorsum to 60 degrees C water or 30 degrees C water for 18 seconds, respectively (n = 4/group). Heterotopic bone volume was analyzed in vivo by micro-computed tomography for 3 months. Histological analysis of vasculogenesis was performed with platelet endothelial cell adhesion molecule staining. Osteogenic histological analysis was performed by Safranin O, Picrosirius red, and aniline blue staining. Qualitative analysis of heterotopic bone composition was completed with ex vivo Raman spectroscopy.
Results: Subcutaneously implanted ossicles formed heterotopic bone. Ossicles from mice with burn injuries developed significantly more bone than sham control mice, analyzed by micro-computed tomography at 1, 2, and 3 months (P < 0.05), and had enhanced early and late endochondral ossification as demonstrated by Safranin O, Picrosirius red, and aniline blue staining. In addition, burn injury enhanced vascularization of the ossicles (P < 0.05). All ossicles demonstrated chemical composition characteristic of bone as demonstrated by Raman spectroscopy.
Conclusions: Burn injury increases the predilection to osteogenic differentiation of ectopically implanted ossicles. Early differences in vascularity correlated with later bone development. Understanding the role of burn injury on heterotopic bone formation is an important first step toward the development of treatment strategies aimed to prevent unwanted and detrimental heterotopic bone formation.
Details
- Title: Subtitle
- Burn Injury Enhances Bone Formation in Heterotopic Ossification Model
- Creators
- Jonathan R. Peterson - University of MichiganSara De La Rosa - University of MichiganHongli Sun - University of MichiganOluwatobi Eboda - University of MichiganKatherine E. Cilwa - University of MichiganAlexis Donneys - University of MichiganMichael Morris - University of MichiganSteven R. Buchman - University of MichiganPaul S. Cederna - University of MichiganPaul H. Krebsbach - Biomedical Engineering - Medical SchoolStewart C. Wang - University of MichiganBenjamin Levi - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Annals of surgery, Vol.259(5), pp.993-998
- DOI
- 10.1097/SLA.0b013e318291da85
- PMID
- 23673767
- PMCID
- PMC4498401
- NLM abbreviation
- Ann Surg
- ISSN
- 0003-4932
- eISSN
- 1528-1140
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 6
- Grant note
- T32GM008616 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) K08 GM109105; T32 GM008616 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 05/01/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery
- Record Identifier
- 9984367732902771
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