NanoEngineering Group, Faculty of Mechanical Engineering, Technion─Israel Institute of Technology, Haifa 3200003, Israel.
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Biomacromolecules. 2022 Aug 8;23(8):3222-3234. doi: 10.1021/acs.biomac.2c00316. Epub 2022 Jun 30.
The present work dealt with the development of physically cross-linked injectable hydrogels with potential applications in tissue engineering. The hydrogels were composed of a ternary mixture of a polyanion and a polyampholyte, hyaluronic acid (HA) and gelatin, respectively, bridged by cationic cellulose nanocrystals (cCNCs). A 3D network is formed by employing attractive electrostatic interactions and hydrogen bonding between these components under physiological conditions. The hydrogels demonstrated low viscosity at high stresses, enabling easy injection, structural stability at low stresses (<15 Pa), and nearly complete structure recovery within several minutes. Increasing the cCNC content (>3%) reduced hydrogel swelling and decelerated the degradation in phosphate-buffered saline as compared to that in pure HA and HA-gelatin samples. Biological evaluation of the hydrogel elutions showed excellent cell viability. The proliferation of fibroblasts exposed to elutions of hydrogels with 5% cCNCs reached ∼200% compared to that in the positive control after 11 days. Considering these results, the prepared hydrogels hold great potential in biomedical applications, such as injectable dermal fillers, 3D bioprintable inks, or 3D scaffolds to support and promote soft tissue regeneration.
本工作开发了具有组织工程应用潜力的物理交联型可注射水凝胶。该水凝胶由聚阴离子和聚两性电解质、透明质酸（HA）和明胶的三元混合物组成，分别由阳离子纤维素纳米晶体（cCNC）桥接。在生理条件下，这些组分之间通过静电吸引力和氢键形成 3D 网络。该水凝胶在高应变速率下具有低粘度，便于注射，在低应变速率（<15 Pa）下具有结构稳定性，并且在几分钟内几乎完全恢复结构。与纯 HA 和 HA-明胶样品相比，增加 cCNC 含量（>3%）会降低水凝胶的溶胀度并减缓在磷酸盐缓冲盐水中的降解速度。水凝胶浸提液的生物学评价显示出良好的细胞活力。与阳性对照相比，暴露于含 5%cCNC 的水凝胶浸提液中的成纤维细胞增殖在 11 天后达到约 200%。考虑到这些结果，所制备的水凝胶在生物医学应用中具有巨大的潜力，例如可注射的皮肤填充物、3D 可生物打印墨水或 3D 支架，以支持和促进软组织再生。
