Chitosan (CS) hydrogels have been widely used throughout basic tissue engineering and regenerative medicine research and it is very desirable to develop advanced CS materials with superior mechanical and topographical properties for more extensive applications. Herein, we present the design of a double crosslinking pure CS hydrogel material via the synergic effect of the chemical covalent network, hydrophobic interactions, enhanced intermolecular hydrogen bonding and the formation of the CS crystallite. The resultant pure CS hydrogel possesses increases in strength and toughness by two orders of magnitude (fracture energy ∼7.733 J m⁻²; maximal compression stress ∼10.81 MPa, elastic modulus ∼1.33 MPa). We utilize ¹H NMR and FT-IR to prove the success of chemical modification. The results of Raman spectra and WXRD have proved the existence of physical interaction between CS hydrogels and microcrystals, thus explaining the enhancement mechanism of mechanical strength of CS hydrogel. The live and death results also show that MSCs can grow well on CS hydrogels, and the results of CCK-8 indicate low cytotoxicity of CS hydrogels. This CS hydrogel shows great potential applications in tissue engineering and regenerative medicine.

壳聚糖 (CS) 水凝胶已广泛用于基础组织工程和再生医学研究，因此非常需要开发具有优异机械和形貌特性的先进 CS 材料以用于更广泛的应用。在这里，我们通过化学共价网络、疏水相互作用、增强的分子间氢键和 CS 微晶的形成的协同作用，提出了一种双交联纯 CS 水凝胶材料的设计。所得纯 CS 水凝胶的强度和韧性提高了两个数量级（断裂能 ~7.733 J m ^-2；最大压缩应力 ~10.81 MPa，弹性模量 ~1.33 MPa）。我们利用¹H NMR和FT-IR证明化学修饰成功。拉曼光谱和WXRD结果证明了CS水凝胶与微晶之间存在物理相互作用，从而解释了CS水凝胶机械强度的增强机制。生死结果也表明MSCs可以在CS水凝胶上生长良好，CCK-8的结果表明CS水凝胶的细胞毒性较低。这种 CS 水凝胶在组织工程和再生医学中显示出巨大的潜在应用。