Department of Biomedical Engineering, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA.
Ann Biomed Eng. 2019 Aug;47(8):1701-1710. doi: 10.1007/s10439-019-02282-5. Epub 2019 May 1.
Alginate hydrogels have been extensively used and successfully validated as delivery vehicles of bioactive factors in many tissue engineering applications. This work describes and characterizes a singular alternative method to create alginate hydrogels designated as thaw-induced gelation (TIG). The TIG method involves gelation through the time-dependent release of the polymer or crosslinker by melting into solution. Alginate TIG hydrogels were validated for spatial-temporal control delivery of different cargos including albumin, dextran, and doxorubicin. Chitosan was incorporated into TIG hydrogels to investigate the electrostatic interactions between alginate and the tested cargos. Interestingly, while 90% of doxorubicin was released after 8 h from hydrogels formed with frozen calcium, hydrogels formulated from frozen alginate took 72 h. In addition, the storage modulus of TIG hydrogels prepared from frozen alginate was double that of a hydrogel formed without freezing alginate. Therefore, the utility of TIG strategies are particularly promising for the delivery of therapeutic cargos smaller than the mesh size of the alginate hydrogel, as it enables controlled release of these cargos without any further chemical modifications of the hydrogels. These TIG alginate hydrogels with tunable mechanical properties and control over the delivery of smaller cargos could be useful in many tissue engineering applications.
海藻酸盐水凝胶已被广泛应用，并在许多组织工程应用中成功验证为生物活性因子的输送载体。本工作描述并表征了一种独特的替代方法来创建海藻酸盐水凝胶，称为解冻诱导凝胶化（TIG）。TIG 方法通过将聚合物或交联剂融化到溶液中，通过时间依赖性释放来实现凝胶化。海藻酸盐 TIG 水凝胶被验证用于包括白蛋白、葡聚糖和阿霉素在内的不同载药的时空控制释放。壳聚糖被掺入 TIG 水凝胶中，以研究海藻酸盐与所测试载药之间的静电相互作用。有趣的是，虽然 90%的阿霉素在冷冻钙离子形成的水凝胶中 8 小时后释放，但在冷冻海藻酸盐形成的水凝胶中则需要 72 小时。此外，由冷冻海藻酸盐制备的 TIG 水凝胶的储能模量是未冷冻海藻酸盐形成的水凝胶的两倍。因此，TIG 策略对于输送小于海藻酸盐水凝胶网孔尺寸的治疗性载药特别有前景，因为它可以在不对水凝胶进行任何进一步化学修饰的情况下控制这些载药的释放。这些具有可调机械性能和对较小载药输送控制的 TIG 海藻酸盐水凝胶可能在许多组织工程应用中非常有用。
