The role of thrombospondins in wound healing, ischemia, and the foreign body reaction.
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ABSTRACT:
SUBMITTER: Kyriakides TR
PROVIDER: S-EPMC2778594 | biostudies-other | 2009 Dec
REPOSITORIES: biostudies-other
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Project description:Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of macrophages in the development of FBR. This study profiles gene expression of in vitro fibrinogen activated macrophages as well as that of freshly isolated macrophages from 3-days implants, against a background of unactivated macrophages/monocytes. Total RNA was isolated from fibrinogen activated macrophages, FBR macrophages and macrophages from blood (control). Samples were processed in triplicate on Rat Genome 230 2.0 Array GeneChips, adding up to 9 arrays in total. Microarray processing was performed at DNAVision (Charleroi, Belgium). The RMA comparisons between macrophases are linked below.
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Project description:Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of macrophages in the development of FBR. This study profiles gene expression of in vitro fibrinogen activated macrophages as well as that of freshly isolated macrophages from 3-days implants, against a background of unactivated macrophages/monocytes.
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Project description:IntroductionEpoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice.MethodsIschemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-?, TGF-?, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1? were evaluated immunohistochemically in wounds on day 3, 6, and 9.ResultsIschemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-?, TGF-?, SDF-1?, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-?, and SDF-1? expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone.ConclusionIn summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia.
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Project description:Electrospun materials have been widely explored for biomedical applications because of their advantageous characteristics, i.e., tridimensional nanofibrous structure with high surface-to-volume ratio, high porosity, and pore interconnectivity. Furthermore, considering the similarities between the nanofiber networks and the extracellular matrix (ECM), as well as the accepted role of changes in ECM for hernia repair, electrospun polymer fiber assemblies have emerged as potential materials for incisional hernia repair. In this work, we describe the application of electrospun non-absorbable mats based on poly(ethylene terephthalate) (PET) in the repair of abdominal defects, comparing the performance of these meshes with that of a commercial polypropylene mesh and a multifilament PET mesh. PET and PET/chitosan electrospun meshes revealed good performance during incisional hernia surgery, post-operative period, and no evidence of intestinal adhesion was found. The electrospun meshes were flexible with high suture retention, showing tensile strengths of 3 MPa and breaking strains of 8-33%. Nevertheless, a significant foreign body reaction (FBR) was observed in animals treated with the nanofibrous materials. Animals implanted with PET and PET/chitosan electrospun meshes (fiber diameter of 0.71 ± 0.28 µm and 3.01 ± 0.72 µm, respectively) showed, respectively, foreign body granuloma formation, averaging 4.2-fold and 7.4-fold greater than the control commercial mesh group (Marlex). Many foreign body giant cells (FBGC) involving nanofiber pieces were also found in the PET and PET/chitosan groups (11.9 and 19.3 times more FBGC than control, respectively). In contrast, no important FBR was observed for PET microfibers (fiber diameter = 18.9 ± 0.21 µm). Therefore, we suggest that the reduced dimension and the high surface-to-volume ratio of the electrospun fibers caused the FBR reaction, pointing out the need for further studies to elucidate the mechanisms underlying interactions between cells/tissues and nanofibrous materials in order to gain a better understanding of the implantation risks associated with nanostructured biomaterials.
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