Development of hydrogels based on oxidized cellulose sulfates and carboxymethyl chitosan

Development of hydrogels based on oxidized cellulose sulfates and carboxymethyl chitosan
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基于氧化纤维素硫酸盐和羧甲基壳聚糖的水凝胶的开发

DOI:
10.1007/s10570-019-02596-6
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发表时间:
2019
期刊:
影响因子:
5.7
通讯作者:
S. Fischer
S. Fischer
中科院分区:
材料科学2区
文献类型:
--
作者:
J. Strätz;A. Liedmann;M.-L. Trutschel;K. Mäder;T. Groth;S. Fischer

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纤维素或壳聚糖代表了组织工程中所需的具有优异生物相容性的高度丰富的生物聚合物。纤维素和壳聚糖都可以用来形成水凝胶,可以替代软骨等人体软组织。因此,我们在这里开发了一种方法来氧化硫酸化后的纤维素,然后与羧甲基壳聚糖(CMCh)交联。通过直接硫酸化或乙酰硫酸化进行硫酸化,达到DSSulf = 0.8-2.0的不同硫酸化度。随后用高碘酸钠进行纤维素硫酸盐(CS)的氧化,其产生DSAld = 0.1-0.3的醛含量。由于氧化需要CS的脱水葡萄糖单元(AGU)中存在邻位羟基,因此通过直接硫酸化(包括C2和C3位的羟基)获得的较高硫酸化程度产生较低的醛含量。相反,通过乙酰硫酸化在C6-位的区域选择性硫酸化更适合于实现更高的CS氧化度。因此,当氧化程度高而硫酸化程度低时,通过氧化纤维素硫酸酯(oCS)与CMh的化学交联获得的水凝胶形成在数秒内是快速的。硫酸化程度高时,凝胶形成时间约为24 h。还可以表明,当在磷酸盐缓冲盐水(PBS)或Dulbeccos改良的Eagle培养基(DMEM)中孵育时,aDSAId为0.28或更高的基于oCS的水凝胶稳定25天。使用pH依赖性荧光示踪剂分子的研究可以表明,当水凝胶在pH 7.4的PBS中孵育时,水凝胶中的固有pH值为微酸性(pH 6.4)。通过NMR研究了凝胶网络的传质和均匀性,发现水分子的扩散在水凝胶内部没有受到阻碍。
Cellulose or chitosan represent highly abundant biopolymers possessing excellent biocompatibility that is required in tissue engineering. Both, cellulose and chitosan can be used to form hydrogels that can replace soft human tissues like cartilage. Hence, we developed here an approach to oxidize cellulose after sulfation, which was then crosslinked with carboxymethyl chitosan (CMCh). Sulfation was performed either by direct or acetosulfation reaching different sulfation degrees ofDSSulf= 0.8–2.0. Subsequently oxidation of cellulose sulfate (CS) was performed with sodium periodate, which yielded aldehyde contents ofDSAld= 0.1–0.3. Since oxidation requires the presence of vicinal hydroxyl groups in the anhydroglucose unit (AGU) of CS, higher sulfation degree as obtained by direct sulfation including hydroxyl groups at C2 and C3-position yielded lower aldehyde contents. On the contrary, regioselective sulfation at C6-position by acetosulfation was more suitable to achieve higher oxidation degrees of CS. Consequently, hydrogel formation obtained by chemical crosslinking of oxidized cellulose sulfate (oCS) with CMCh was fast within seconds when oxidation degree was high, but sulfation degree low. Moreover gel formation lasted almost 24 h when sulfation degree was high. It could also be shown that hydrogels based on oCS with aDSAldof 0.28 or higher were stable for 25 days when incubated in phosphate-buffered saline (PBS) or Dulbeccos modified Eagle medium (DMEM). Studies with pH dependent fluorescent tracer molecules could show that the intrinsic pH value in hydrogels was slightly acidic (pH 6.4) when they were incubated in PBS at pH 7.4. Mass transfer and homogeneity of the gel network was studied by NMR finding that diffusion of water molecules was not hindered inside the hydrogels.
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