Injectable silk-polyethylene glycol hydrogels
Injectable silk-polyethylene glycol hydrogels
复制标题
可注射丝聚乙二醇水凝胶。
DOI：
10.1016/j.actbio.2014.10.027
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发表时间：
2015-01-15
影响因子：
9.7
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Wang, Xiaoqin;Partlow, Benjamin;Kaplan, David L.
用于组织修复的丝水凝胶通常通过化学或物理处理从丝溶液预形成。对于许多医学应用，期望利用高浓度（>8%）的可注射丝水凝胶以避免手术植入并实现凝胶的缓慢体内降解。在本研究中，通过将丝与低分子量聚乙二醇（PEG），特别是PEG 300和400（分子量300和400 g mol（-1））混合来产生原位形成水凝胶的可注射丝溶液。甘氨酰化时间依赖于PEG的浓度和分子量。当凝胶中PEG的浓度达到40- 45%时，凝胶化时间小于30分钟，如通过光密度测量和流变学研究所揭示的，PEG 400的动力学比PEG 300快。Geladon伴随着丝的结构变化，导致从溶液中的无规卷曲到凝胶中的结晶β-片层的转化，基于圆二色性、衰减全反射傅里叶变换红外光谱和X-射线衍射。测定的模量（127.5kPa）和屈服强度（11.5kPa）与相同浓度的丝的超声诱导的水凝胶的模量和屈服强度相当。15%PEG-丝水凝胶通过27 G针的时间依赖性注射显示出在60 min内从类似于10 N到50 N的压缩力逐渐增加。PEG-丝水凝胶上的人间充质干细胞的生长受到阻碍，可能是由于PEG的存在，其在5天延迟后生长，推测是当PEG从凝胶中溶解时。当5%PEG-丝素水凝胶皮下注射到大鼠体内时，超声成像和组织学分析显示，20天后发生显著降解和组织向内生长。在凝胶周围未观察到显著炎症。可注射性、缓慢降解和低初始细胞附着的特征表明这些PEG-丝水凝胶对于许多生物医学应用（例如防污和抗粘附）是感兴趣的。(C)2014 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Silk hydrogels for tissue repair are usually pre-formed via chemical or physical treatments from silk solutions. For many medical applications, it is desirable to utilize injectable silk hydrogels at high concentrations (>8%) to avoid surgical implantation and to achieve slow in vivo degradation of the gel. In the present study, injectable silk solutions that formed hydrogels in situ were generated by mixing silk with low-molecular-weight polyethylene glycol (PEG), especially PEG300 and 400 (molecular weight 300 and 400 g mol(-1)). Gelation time was dependent on the concentration and molecular weight of PEG. When the concentration of PEG in the gel reached 40-45%, gelation time was less than 30 min, as revealed by measurements of optical density and rheological studies, with kinetics of PEG400 faster than PEG300. Geladon was accompanied by structural changes in silk, leading to the conversion from random coil in solution to crystalline beta-sheets in the gels, based on circular dichroism, attenuated total reflection Fourier transform infrared spectroscopy and X-ray diffraction. The modulus (127.5 kPa) and yield strength (11.5 kPa) determined were comparable to those of sonication-induced hydrogels at the same concentrations of silk. The time-dependent injectability of 15% PEG-silk hydrogel through 27 G needles showed a gradual increase of compression forces from similar to 10 to 50 N within 60 min. The growth of human mesenchymal stem cells on the PEG-silk hydrogels was hindered, likely due to the presence of PEG, which grew after a 5 day delay, presumably while the PEG solubilized away from the gel. When 5% PEG-silk hydrogel was subcutaneously injected in rats, significant degradation and tissue in-growth took place after 20 days, as revealed by ultrasound imaging and histological analysis. No significant inflammation around the gel was observed. The features of injectability, slow degradation and low initial cell attachment suggests that these PEG-silk hydrogels are of interest for many biomedical applications, such as anti-fouling and anti-adhesion. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.