关键词: 智能材料, 明胶, 单宁, 四硼酸钠, 双醛纳米纤维素, 多重氢键, 自愈合水凝胶, 生物相容性

Abstract:

Objective Hydrogel materials have a wide range of promising applications in various fields such as drug delivery, tissue healing, and wearable electronic devices because of their soft texture and 3-D porous structure. However, the low durability and poor biocompatibility of traditional hydrogels have limited their practical applications. Therefore, a self-healing hydrogel with good biocompatibility and injectable capacity should be designed to provide novel perspectives to break the current technological bottleneck.
Method The self-healing property of hydrogels depends mainly on dynamic chemical bonding, which restores damaged chemical bonds and resumes the hydrogel to its original properties. Biocompatible nanocellulose self-healing hydrogels (Gel/DNCC/Borax/Ta) with triple crosslinking networks were prepared by reversible crosslinking the amino group in gelatin (Gel) and the aldehyde group in dual formaldehyde nanocellulose (DNCC) to form imine bonds as the first crosslinking network. Then tannin (Ta) and borax(Borax) were introduced into the hydrogels to form multiple hydrogen bonding network and dynamic borate ester bonding network.
Results The thermal stability of Gel/DNCC/Borax/Ta hydrogels was enhanced compared to gelatin, with the thermal decomposition temperature increasing from 277.3 ℃ to 301.0 ℃, and the maximum mass loss rate temperature increasing from 312.9 ℃ to 320.9 ℃. Compared with Gel/DNCC hydrogel, the mechanical properties and colloidal viscoelasticity of Gel/DNCC/Borax/Ta hydrogel were significantly enhanced, with the fracture strength increasing from 0.138 MPa to 0.353 MPa, representing an increase of 155.7%, and the compressive strength increasing from 0.686 MPa to 1.422 MPa, and the energy storage modulus increasing from 960 Pa to 1 550 Pa with an increase of 61.4%. The beneficial thermal and mechanical properties of Gel/DNCC/Borax/Ta hydrogels was due to the synergistic effect of multiple hydrogen bonds and dynamic covalent bonds in the hydrogels, forming a compact triple cross-linked network, thus enhancing their structural stability and improving their thermal stability. The human prosthetic hand model fitting experiments showed that Gel/DNCC/Borax/Ta hydrogel could follow body movement with good flexibility. Syringe injection experiments showed that Gel/DNCC/Borax/Ta hydrogels had good flowability and gelation ability. The cut hydrogel could heal itself and keep its original shape within 1 h at room temperature. The compressive strain of Gel/DNCC/Borax/Ta hydrogel before after healing was 0.519 and 0.509 mm/mm with a self-healing efficiency of 98%, respectively. This indicats the outstanding healing ability of Gel/DNCC/Borax/Ta hydrogel. The self-healing property of the hydrogel is derived from the dynamic borate ester and imine bonds that are re-formed and healed rapidly by their dynamic reversibility after being disrupted during the self-healing process. Detection of the proliferation of fibroblasts treated with various concentrations of gelatin cellulose complex extracts by the CCK8 method. The results showed that 0.5% of gelatin cellulose complex extracts had a well promotion effect on cell proliferation. Flow cytometry was used to measure fibroblast survival, and fibroblasts treated with an infusion containing 0.5% gelatin cellulose complex still had less than 5% apoptosis after 72 h. Cell staining assay showed that fibroblasts were able to survive normally in 0.5% of gelatin cellulose complex extracts.
Conclusion A self-healing hydrogel with good biocompatibility and injectability is developed to solve the problems of low durability and poor biocompatibility that existed in hydrogel materials, which obstructed their applications in wearable electronic devices, tissue healing, and drug delivery. The three-dimensional interpenetrating network structure endows the Gel/DNCC/Borax/Ta hydrogel with strong mechanical properties, thermal stability and good elasticity. The dynamic borate ester bonds and imine bonds give Gel/DNCC/Borax/Ta hydrogels a strong self-healing ability, enabling them to self-heal within 1 h after damage, with a self-healing efficiency of 98%. Since gelatin, a high molecular mass water-soluble protein mixture, can act as a cell culture substrate to promote cell proliferation, DNCC also possesses excellent biocompatibility, giving the Gel/DNCC/Borax/Ta hydrogel a high degree of biocompatibility. Favorable thermal stability, mechanical properties including injectability and flexibility, and biocompatibility give the hydrogel promising potential for use in biomedical and tissue engineering.

Key words: smart material, gelatin, tannin, borax, dual formaldehyde nanocellulose, multiple hydrogen bond, self-healing hydrogel, biocompatibility