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ABSTRACT: Heterotopic ossification (HO) develops in the extremities of wounded service members and is common in the setting of high‐energy penetrating injuries and blast‐related amputations. No safe and effective prophylaxis modality has been identified for this patient population. Palovarotene has been shown to reduce bone formation in traumatic and genetic models of HO. The purpose of this study was to determine the effects of Palovarotene on inflammation, progenitor cell proliferation, and gene expression following a blast‐related amputation in a rodent model (n = 72 animals), as well as the ability of Raman spectroscopy to detect early HO before radiographic changes are present. Treatment with Palovarotene was found to dampen the systemic inflammatory response including the cytokines IL‐6 (p = 0.01), TNF‐α (p = 0.001), and IFN‐γ (p = 0.03) as well as the local inflammatory response via a 76% reduction in the cellular infiltration at post‐operative day (POD)‐7 (p = 0.03). Palovarotene decreased osteogenic connective tissue progenitor (CTP‐O) colonies by as much as 98% both in vitro (p = 0.04) and in vivo (p = 0.01). Palovarotene treated animals exhibited significantly decreased expression of osteo‐ and chondrogenic genes by POD‐7, including BMP4 (p = 0.02). Finally, Raman spectroscopy was able to detect differences between the two groups by POD‐1 (p < 0.001). These results indicate that Palovarotene inhibits traumatic HO formation through multiple inter‐related mechanisms including anti‐inflammatory, anti‐proliferative, and gene expression modulation. Further, that Raman spectroscopy is able to detect markers of early HO formation before it becomes radiographically evident, which could facilitate earlier diagnosis and treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1135–1144, 2018. [ABSTRACT FROM AUTHOR]

A bstract The pathologic development of heterotopic ossification (HO) is well described in patients with extensive trauma or with hyperactivating mutations of the bone morphogenetic protein (BMP) receptor ACVR1. However, identification of progenitor cells contributing to this process remains elusive. Here we show that connective tissue cells contribute to a substantial amount of HO anlagen caused by trauma using postnatal, tamoxifen-inducible, scleraxis-lineage restricted reporter mice ( Scx-creERT2/tdTomatofl/fl). When the scleraxis-lineage is restricted specifically to adults prior to injury marked cells contribute to each stage of the developing HO anlagen and coexpress markers of endochondral ossification (Osterix, SOX9). Furthermore, these adult preinjury restricted cells coexpressed mesenchymal stem cell markers including PDGFRα, Sca1, and S100A4 in HO. When constitutively active ACVR1 ( caACVR1) was expressed in scx-cre cells in the absence of injury ( Scx-cre/caACVR1fl/fl), tendons and joints formed HO. Postnatal lineage-restricted, tamoxifen-inducible caACVR1 expression ( Scx-creERT2/caACVR1fl/fl) was sufficient to form HO after directed cardiotoxin-induced muscle injury. These findings suggest that cells expressing scleraxis within muscle or tendon contribute to HO in the setting of both trauma or hyperactive BMP receptor (e.g., caACVR1) activity. S tem C ells 2017;35:705-710 [ABSTRACT FROM AUTHOR]

Herein we report a facile layer-by-layer method for creating an antimicrobial coating composed of silver nanoparticles on medical grade titanium test discs. Nanoscale silver nanoparticle layers are attached to the titanium orthopedic implant material via aminopropyltriethoxy silane crosslinker that reacts with neighboring silane moieties to create an interconnected network. A monolayer of silane, followed by a monolayer of silver nanoparticles would form one self-assembled layer and this process can be repeated serially, resulting in increased silver nanoparticles deposition. The release rate of silver ion increases predictably with increasing numbers of layers and at appropriate thicknesses these coatings demonstrate 3–4 log reduction of viable Escherichia coli and Staphylococcus aureus bacteria. Increasing the thickness of the coatings resulted in reduced bacterial colonization as determined by fluorescent staining and image analysis. Interestingly, the cytotoxicity of murine 3T3 cells as quantified by fluorescent staining and flow cytometry, was minimal and did not vary significantly with the coating thickness. Additionally, these coatings are mechanically stable and resist delamination by orthogonal stress test. This simple layer-by-layer coating technique may provide a cost-effective and biocompatible method for reducing microbial colonization of implantable orthopedic devices. [ABSTRACT FROM AUTHOR]

Annually, more than 200,000 elective liposuction procedures are performed in the United States and over a million worldwide. The ease of harvest and abundance make human adipose-derived stromal/stem cells (hASCs) isolated from lipoaspirates an attractive, readily available source of adult stem cells that have become increasingly popular for use in many studies. Here, we describe common methods for hASC culture, preservation, and osteogenic differentiation. We introduce methods of ceramic, polymer, and composite scaffold synthesis with a description of morphological, chemical, and mechanical characterization techniques. Techniques for scaffold loading are compared, and methods for determining cell loading efficiency and proliferation are described. Finally, we provide both qualitative and quantitative techniques for in vitro assessment of hASC osteogenic differentiation., (© 2014 Elsevier Inc. All rights reserved.)