Novel sustained releasing triamcinolone acetonide polyesteramide microparticle platfform to reduce pain in the knee of a synoviatis rat model

N. Woike, I Rudnik-Jansen, A. Tellegen, L. Creemers, M. Tryfonidou, G. Mihov, J.C. Thies, K. Schrijver, S.A. Versteeg, N. Eijkelkamp

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Abstract

used image J software. Each slide was divided into synovial and fat sectors based on the content. The software measured each marker in the synovial and fat sectors separately and combined. Further analysis followed regrouping patients into two groups based on fat cell diameter, measured as small (<68 mm) and large (>68 mm) fat cells. The IHC markers were reanalyzed based on the fat cell size. Additional manual counts, vessel diameter and distance to the synovial surface, were undertaken on vessels in the synovial and fat sectors. A synovitis score was determined using the H&E stained sections (Krenn et al., 2006). Results: Using the initial grouping, overall vascularity did not show any significant differences (p¼0.468); vimentin positivity was significantly reduced in the old lean group (p¼0.006), and inflammatory markers showed a trend of increasing with increase BMI. Regrouping patients based on fat cell size revealed multiple significant differences. Macrophages, T cells, B cells and fibroblasts positivity was significantly higher in the pres-ence of big fat cells (p¼ 0.035, 0.016, 0.046, 0.014 respectively). The vascular density was significantly higher in the fatty sections with big fat cells (p¼ 0.028). Inflammatory markers showed positive correlation with BMI and negative correlation with age. An increasing trend of vascular density, the distance to the synovial surface and vascular wall thickness was observed in the young obese group. There was no clear difference between the groups in relation to synovitis but majority of patients showed mild grade synovitis. Conclusions: The synovium of the obese patients showed more inflammatory response but the vascularity was not significantly dif-ferent. Increased fat cell size attracted significantly more inflammatory cells. Moreover, vascular hyperplasia, which was noticed mainly in the obese people, could be an indication of atherosclerosis in the synovial vessels. Low grade synovitis is common in primary knee OA. This image showed H&E stain of the synovium of an obese person. The vessels has increased wall thickness very close to the intimal surface. Purpose: Inflammation in an osteoarthritic joint predominantly causes pain and stimulates cartilage matrix breakdown. Triamcinolone aceto-nide (TAA) is intra-articularly injected to alleviate pain and temporarily reduce inflammation. Since multiple injections entail risks, local sus-tained TAA release can overcome such disadvantages. PLGA for-mulations of TAA has been shown to effectively prolong pain inhibition in OA, but limited to 4 weeks. A novel polyesteramide (PEA) micro-sphere platform based on natural a-amino acids previously showed
Original languageEnglish
Pages (from-to)S119
JournalOsteoarthritis and Cartilage
Volume26
DOIs
Publication statusPublished - Apr 2018

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