Cell-adhesive thermogelling PNIPAAm/hyaluronic acid cell delivery hydrogels for potential application as minimally invasive retinal therapeutics

Cell-adhesive thermogelling PNIPAAm/hyaluronic acid cell delivery hydrogels for potential application as minimally invasive retinal therapeutics
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DOI:
10.1002/jbm.a.34021
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发表时间:
2012-07-01
影响因子:
4.9
通讯作者:
Sheardown, Heather
Sheardown, Heather
中科院分区:
工程技术3区
文献类型:
--
作者:
Mazumder, M. A. Jafar;Fitzpatrick, Scott D.;Sheardown, Heather

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通过自由基聚合法合成了N-异丙基丙烯酰胺(NIPAAm)和丙烯酸-N-羟基琥珀酰亚胺(NAS)的共聚物,并将其与胺基官能化透明质酸(HA)和细胞黏附性RGDS多肽偶联。这些新型共聚物旨在促进液体悬浮细胞进入微妙的视网膜下空间的非侵入性输送,用于治疗视网膜退行性疾病,如老年性黄斑变性(AMD)和糖尿病视网膜病变。各种合成的共聚物都表现出亚生理相变温度,从而允许温度诱导支架的形成和移植细胞随后被困在粘附性支撑基质中。用傅里叶变换红外光谱(FTIR)和核磁共振氢谱(1H核磁共振)对接枝成功的HA和RGDS多肽进行了表征。所有共聚物在培养中与视网膜色素上皮(RPE)细胞表现出良好的相容性,并且在皮下接种无毛SKH1-E小鼠(品系代码447)后观察到最小的宿主反应。(C)2012年威利期刊,Inc.生物材料研究公司2012年A部分。
Copolymers of N-isopropylacrylamide (NIPAAm) and acrylic acid N-hydroxysuccinimide (NAS) were synthesized via free radical polymerization and conjugated with amine-functionalized hyaluronic acid (HA) and cell adhesive RGDS peptides. These novel copolymers were designed to facilitate noninvasive delivery of a liquid suspension of cells into the delicate subretinal space for treatment of retinal degenerative diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. The various synthesized copolymers all displayed subphysiological phase transition temperatures, thereby allowing temperature-induced scaffold formation and subsequent entrapment of transplanted cells within an adhesive support matrix. Successful grafting of HA and RGDS peptides were confirmed with Fourier Transform Infrared (FTIR) spectroscopy and quantified with 1H Nuclear Magnetic Resonance (NMR) spectroscopy. All copolymers demonstrated excellent compatibility with retinal pigment epithelial (RPE) cells in culture and minimal host response was observed following subcutaneous implantation into hairless SKH1-E mice (strain code 447). (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 2012.