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可注射丝-聚乙二醇水凝胶。

Injectable silk-polyethylene glycol hydrogels.

机构信息

National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, China; Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.

National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, China; Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.

出版信息

Acta Biomater. 2015 Jan;12:51-61. doi: 10.1016/j.actbio.2014.10.027. Epub 2014 Oct 25.


DOI:10.1016/j.actbio.2014.10.027
PMID:25449912
Abstract

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 400g 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 30min, as revealed by measurements of optical density and rheological studies, with kinetics of PEG400 faster than PEG300. Gelation was accompanied by structural changes in silk, leading to the conversion from random coil in solution to crystalline β-sheets in the gels, based on circular dichroism, attenuated total reflection Fourier transform infrared spectroscopy and X-ray diffraction. The modulus (127.5kPa) and yield strength (11.5kPa) 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 27G needles showed a gradual increase of compression forces from ∼10 to 50N within 60min. 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.

摘要

用于组织修复的丝素水凝胶通常通过化学或物理处理从丝素溶液中预先形成。对于许多医学应用,期望利用可注射的丝素水凝胶以高浓度(>8%)来避免手术植入,并实现凝胶在体内的缓慢降解。在本研究中,通过混合丝素与低分子量聚乙二醇(PEG),特别是 PEG300 和 400(分子量 300 和 400g mol(-1)),生成了可原位形成水凝胶的可注射丝素溶液。凝胶时间取决于 PEG 的浓度和分子量。当凝胶中 PEG 的浓度达到 40-45%时,凝胶时间小于 30min,这是通过测量光密度和流变学研究揭示的,PEG400 的动力学比 PEG300 快。凝胶化伴随着丝素结构的变化,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,导致溶液中无规卷曲向凝胶中结晶β-折叠的转变。确定的模量(127.5kPa)和屈服强度(11.5kPa)与相同浓度丝素的超声诱导水凝胶相当。通过 27G 针头的 15%PEG-丝素水凝胶的时变可注射性显示出在 60min 内从约 10 到 50N 的压缩力的逐渐增加。人骨髓间充质干细胞在 PEG-丝素水凝胶上的生长受到阻碍,这可能是由于 PEG 的存在,PEG 在延迟 5 天后生长,可能是因为 PEG 从凝胶中溶解出来。当 5%PEG-丝素水凝胶在大鼠皮下注射时,20 天后通过超声成像和组织学分析观察到明显的降解和组织内生长。在凝胶周围没有观察到明显的炎症。可注射性、缓慢降解和初始细胞附着低的特点表明,这些 PEG-丝素水凝胶在许多生物医学应用中很有意义,例如抗污染和抗粘连。

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