2017-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656676摘要：本計畫源於104-2314-B-002-199三年期計畫’但僅通過一年，本計畫將針對上一期評審之意見加以修訂，並以藍色標記，敬請審查（審查意見表請參閱附件一）。近年許多研究皆指出，當細胞聚集 形成3D micromass，細胞與細胞的接觸增加，於細胞的增生及軟硬組織的分化皆有較佳的效果（含細 胞團打散後的個別細胞，dissociated-cell micromass)，因此本研究擬與共同主持人陽明大學醫工系鍾次 文教授發展新一代具彈性及生物活性之Poly-( e-caprolactone, PCL)-SF為基礎之心肌綴補片及支架， 如：PCL-SF (PS)、PCL-SF/HA/GRGD (PSHG)..等，藉此材料可以誘導骨髓間質幹細胞（BMSC)於材 料上形成BMSC細胞團（BMSC micromass)，作為修復受損心肌區域的新材料。第一年初步研究結果， 發現PSHG心肌綴補片可誘導出BMSC細胞團，且此細胞團具有很高的心肌特異性蛋白表現量 (104-2314-B-002-199計晝執行中）。本兩年期研究計晝，將進行PSHG scaffold之材料特性分析，及 dissociated-BMSC micromass之細胞增生及分化之探討。第一部分，探討PS, PSHG…等scaffold的製 備及特性分析，如：支架孔隙度、機械強度；並探討dissociated-BMSC micromass培養於scaffold上 之增生及心肌分化特性，如：心肌特異性蛋白（Connexin 43, troponin T)染色、RT-PCR定量心肌特異 性基因（Gata4, Nkx2.5)。第二部分，探討心肌綴補片/BMSC植入MI鼠心肌8周後，MI鼠的心肌功 能恢復情形，並藉由心臟超音波、組織染色…等方式，觀察心室擴張、心室壁厚度及心肌功能改善情 形及增進受損心肌區域血管的新生。若獲得足夠經費及時間，將進一步進行支架/dissociated-BMSC micromass系統之動物實驗。藉由本研究採用新PCL-SF基礎材料，針對新一代的PSHG心肌綴補片 或支架於MI大鼠心肌修復功能及機制之探討，可作為臨床轉譯前的重要根據。<br> Abstract: Recently, many researches have reported the benefits of cell micromass. Due to increasing cell-cell interactions after micromass forming, the proliferation and differentiation potential of cells also increase. And so is the dissociated-cell micromass. In addition, our team would like to develop a new elastic and high bioactive PCL-SF based patch and scaffolds incorporated with cardiomyogenesis capacity of BMSC for cardiac repair of MI hearts. Aim of this study is to create a novel biomaterials which can induce BMSC micromass. The preliminary results showed that grafted dual bio-functional molecules onto PCL/SF to produce PCL-SF/HA/GRGD (PSHG) patch induced BMSC micromass with higher cardiac proteins expressions (e.g., Connexin 43) compared with others (104-2314-B-002-199 in execution). In the two-year project, we will develop PSHG scaffold and further investigate the biomaterial properties such as porosity, mechanical force and bioactivity analysis such as proliferation, differentiation properties of dissociated-BMSC micromass examined by confocal microscopy and RT-PCR analysis. For animal studies, the LV remodeling, angiogenesis, wall thickness analysis in the MI zones will be performed as early investigations by this team with ultrasonic imaging system. This study provides an important base for the research cardiac repairs of MI hearts of cardiac patch and scaffolds/BMSC to further perform pre-clinical studies.PCL/蠶絲HAGRGDBMSC細胞團心肌分化/修復PCL/SFHAGRGDBMSC micromasscardiomyogenesiscardiac repairs