Chemical tailoring of gelatin to adjust its chemical and physical properties for functional bioprinting
Chemical tailoring of gelatin to adjust its chemical and physical properties for functional bioprinting
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DOI：
10.1039/c3tb20745e
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发表时间：
2013-01-01
影响因子：
7
通讯作者：
Borchers, Kirsten
中科院分区：
文献类型：
--
作者：
Hoch, Eva;Hirth, Thomas;Borchers, Kirsten
通过甲基丙烯酸酯化和乙酰化游离氨基的明胶的双重化学官能化使得能够控制其溶液的粘性行为和光化学交联后所得水凝胶的机械性能。甲基丙烯酸酯化的程度由所施加的甲基丙烯酸酐的摩尔过量来控制。十倍摩尔过量导致高度甲基丙烯酸酯化明胶（GM（10）），导致具有在喷墨可印刷范围内的低粘度的溶液（10重量%：3.3 +/-0.5mPa·s，37 ℃）和具有高储能模量G'的交联水凝胶（10重量%：15.2 +/-6.4kPa）。两倍过量的甲基丙烯酸酐导致较少的适合于制备软水凝胶的甲基丙烯酸化明胶（GM（2））（10重量%：G' = 9.8 +/-4.6mPa·s），但其溶液是高粘度的（10重量%：14.2 +/-1.1mPa·s，37 ℃），因此易于堵塞印刷喷嘴。在这里，我们表明，额外的乙酰基官能团引入GM 2导致溶液粘度（10重量%：2.9 +/- 0.2 mPa·s，37 ℃）的显着降低，并防止物理凝胶的形成。以这种方式，双重官能化明胶可以被喷墨印刷，同时化学交联度保持低并且所得凝胶是软的。因此，通过明胶的可调节的双重改性，即插入光化学反应性和惰性基团，产生了用于喷墨生物打印的通用生物墨水，其允许处理具有广泛物理性质的基于ECM的水凝胶基质。此外，生物墨水被证明是细胞相容的，并且适合于活哺乳动物细胞的喷墨打印。
Double chemical functionalization of gelatin by methacrylation and acetylation of free amino groups enables control over both the viscous behavior of its solutions and the mechanical properties of the resulting hydrogels after photochemical crosslinking. The degree of methacrylation is controlled by the molar excess of methacrylic anhydride applied. Tenfold molar excess leads to highly methacrylated gelatin (GM(10)), resulting in solutions with low viscosities within the inkjet-printable range (10 wt%: 3.3 +/- 0.5 mPa s, 37 degrees C) and crosslinked hydrogels with high storage moduli G' (10 wt%: 15.2 +/- 6.4 kPa). Twofold excess of methacrylic anhydride leads to less methacrylated gelatin (GM(2)) proper for preparation of soft hydrogels (10 wt%: G' = 9.8 +/- 4.6 mPa s) but its solutions are highly viscous (10 wt%: 14.2 +/- 1.1 mPa s, 37 degrees C) and thus prone to clogging printing nozzles. Here we show that additional introduction of acetyl functionalities into GM2 results in a significant decrease in solution viscosity (10 wt%: 2.9 +/- 0.2 mPa s, 37 degrees C) and prevention of physical gel formation. In such a manner twofold functionalized gelatin can be inkjet-printed while the degree of chemical crosslinking remains low and the resulting gels are soft. Thus, by adjustable twofold modification of gelatin, i.e. inserting photochemically reactive and inert groups, a versatile bioink for inkjet bioprinting is created, which allows for addressing ECM based hydrogel matrices with a broad range of physical properties. Moreover, bioinks are proven to be cytocompatible and proper for inkjet printing of viable mammalian cells.