Raman spectroscopic analysis of combat-related heterotopic ossification development

Crane, Nicole J.; Polfer, Elizabeth M.; Elster, Eric A.; Potter, Benjamin K.; Forsberg, Jonathan A.

doi:10.1016/j.bone.2013.08.026

Cited by 29 publications

(23 citation statements)

References 49 publications

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“…[32,38] Interestingly, the mineral detected at this time point was the complex bone hydroxyapatite (957-962 cm −1 ), suggesting a maturation process from the intermediate phases, and was in all cases associated with collagen.…”

Section: New Matrix Characteristicsmentioning

confidence: 80%

An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network

et al. 2017

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Bone is a dynamic tissue that remodels continuously in response to local mechanical and chemical stimuli. This process can also result in maladaptive ectopic bone in response to injury, yet pathological differences at the molecular and structural levels are poorly understood. A number of in vivo models exist but can often be too complex to allow isolation of factors which may stimulate disease progression. A self‐structuring model of bone formation is presented using a fibrin gel cast between two calcium phosphate ceramic anchors. Femoral periosteal cells, seeded into these structures, deposit an ordered matrix that closely resembles mature bone in terms of chemistry (collagen:mineral ratio) and structure, which is adapted over a period of one year in culture. Raman spectroscopy and X‐ray diffraction confirm that the mineral is hydroxyapatite associated with collagen. Second‐harmonic imaging demonstrates that collagen is organized similarly to mature mouse femora. Remarkably, cells differentiated to the osteocyte phase are linked by canaliculi (as demonstrated with nano‐computed tomography) and remained viable over the full year of culture. It is demonstrated that novel drugs can prevent ossification in constructs. This model can be employed to study bone formation in an effort to encourage or prevent ossification in a range of pathologies.

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Section: New Matrix Characteristicsmentioning

confidence: 80%

An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network

et al. 2017

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“…First, clinically relevant animal models have only recently been developed [21,30]. Second, clinical diagnostic methods are unable to accurately predict the site of HO development [5,20]. Third, analysis of human tissues obtained early in the débridement process has not been performed.…”

Section: Introductionmentioning

confidence: 99%

Early Characterization of Blast-related Heterotopic Ossification in a Rat Model

Qureshi

Crump

Pavey

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) affects the majority of combat-related lower extremity wounds involving severe fracture and amputation. Defining the timing of early osteogenic-related genes may help identify candidate prophylactic agents and guide the timing of prophylactic therapy after blast and other combat-related extremity injuries. Questions/purposes Using a recently developed animal model of combat-related HO, we sought to determine (1) the timing of early chondrogenesis, cartilage formation, and radiographic ectopic bone development; and (2) the early cartilage and bone-related gene and protein patterns in traumatized soft tissue. Methods We used an established rat HO model consisting of blast exposure, controlled femur fracture, crush injury, and transfemoral amputation through the zone of injury. Postoperatively, rats were euthanized on Days 3 to 28. We assessed evidence of early ectopic bone formation by micro-CT and histology and performed proteomic and gene expression analysis. Results All rats showed radiographic evidence of HO within 28 days. Key chondrogenic (collagen type I alpha 1 [COL1a1], p = 0.016) and osteogenic-related genes (RuntThis work was supported by CDMRP (W81XWH-14-2-0010; PI-JAF) and BUMED (602115HP.3720.001.A1014; PI-JAF). Some of the authors are employees of the US Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ''Copyright protection under this title is not available for any work of the United States Government.'' Title 17 U.S.C. §101 defined a US Government work as a work prepared by a military service member or employees of the US Government as part of that person's official duties. The opinions or assertions contained in this paper are the private views of the authors and are not to be construed as reflecting the views, policy or positions of the Department of the Navy, Department of Defense nor the US Government. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research 1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. This work performed at the Naval Medical Research Center, Silver Spring, MD, USA. Conclusions We found that genes that regulate early chondrogenic and osteogenic signaling and bone development (COL1a1, RUNX-2, OCN, PHEX, and POU5F1) are induced early during the tissue reparative/healing phase in a rat model simulating a combat-related extremity injury. Clinical Relevance The ability to correlate molecular events with histologic and morphologic changes will assist re...

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“…The present study supports the use of gene expression at the mRNA level for this purpose. However, one of the most exciting prospects involves the use of Raman spectroscopy, which is a noninvasive tool that could even be used intraoperatively [1]. Still, the variability of the human inflammatory system is difficult to quantify.…”

Section: Dr Leopoldmentioning

confidence: 99%

Editor’s Spotlight/Take 5: Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Leopold

2013

Clin Orthop Relat Res

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Raman spectroscopic analysis of combat-related heterotopic ossification development

Abstract: spectroscopic analysis of combatrelated heterotopic ossification development" (2013).

Cited by 29 publications

References 49 publications

An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network

An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network

Early Characterization of Blast-related Heterotopic Ossification in a Rat Model

Editor’s Spotlight/Take 5: Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

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