Furlani Franco, Sacco Pasquale, Cok Michela, de Marzo Gaia, Marsich Eleonora, Paoletti Sergio, Donati Ivan
Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, I-34127 Trieste, Italy.
Department of Medicine, Surgery, and Health Sciences, University of Trieste, Piazza dell'Ospitale 1, I-34129 Trieste, Italy.
ACS Biomater Sci Eng. 2019 Oct 14;5(10):5539-5547. doi: 10.1021/acsbiomaterials.9b01256. Epub 2019 Sep 13.
The present paper describes an original method to form under physiological conditions homogeneous lactose-modified chitosan (CTL) gels avoiding syneresis. Specifically, combination of boric acid-i.e., the cross-linker-and mannitol-i.e., a polyol competitor for boron binding-were exploited to reduce the very fast kinetics of CTL/boron self-assembly. Resulting gels were homogeneous as proved by scattering analyses. An in-depth rheological characterization was undertaken to identify the correct mannitol-to-boron ratio at which gels showed homogeneity without weakening. Stress sweep and frequency sweep tests were performed to investigate the viscoelastic properties of these dynamic networks, highlighting a marked strain-hardening behavior, which is pivotal in native tissues. Notably, herein we report for the first time that CTL-boric acid gels are multiresponsive systems, whose mechanics can be tailored by different stimuli such as the presence of small molecules like glucose. Moreover, we demonstrate that these networks spontaneously self-heal after breakage. The biocompatibility of such gels was studied under 2D and 3D conditions toward three different cell models, namely, pig primary chondrocytes, human Dental Pulp Stem Cells (hDPSCs), and mouse fibroblasts. Giving the peculiar mechanical performance of selected systems and considering the well-known bioactivity of the chitosan derivative, CTL-boric acid networks are promising candidates as multiresponsive gels to be used in the field of tissue engineering, especially for articular cartilage regeneration.
本文描述了一种在生理条件下形成均一的乳糖修饰壳聚糖（CTL）凝胶且避免脱水收缩的原始方法。具体而言，利用硼酸（即交联剂）和甘露醇（即硼结合的多元醇竞争者）的组合来降低CTL/硼自组装非常快的动力学。散射分析证明所得凝胶是均一的。进行了深入的流变学表征，以确定凝胶显示均一性且不减弱的正确甘露醇与硼的比例。进行了应力扫描和频率扫描测试以研究这些动态网络的粘弹性特性，突出了显著的应变硬化行为，这在天然组织中至关重要。值得注意的是，在此我们首次报道CTL-硼酸凝胶是多响应系统，其力学性能可通过不同刺激（如葡萄糖等小分子的存在）进行调节。此外，我们证明这些网络在断裂后能自发自我修复。在二维和三维条件下研究了此类凝胶对三种不同细胞模型，即猪原代软骨细胞、人牙髓干细胞（hDPSC）和小鼠成纤维细胞的生物相容性。鉴于所选系统独特的力学性能并考虑到壳聚糖衍生物众所周知的生物活性，CTL-硼酸网络有望成为用于组织工程领域的多响应凝胶，特别是用于关节软骨再生。
