Biodegradable self-healing hydrogels are highly desirable materials for therapeutic systems, reusable devices, and intelligent cell/drug carriers. Many research efforts focus on additional functionalities of self-healing hydrogels through physical or chemical strategies/designs. Herein, N-[3-(4-hydroxyphenyl)propanamido] chitosan and a difunctional Pluronic-F127 crosslinker (DF-PF) were synthesized and reacted to form the phenolic-chitosan self-healing hydrogel (CPF) with a high water content (96.5 wt%). Coherent small-angle X-ray scattering (SAXS) analyses of the hydrogel revealed a fast-forming primary fractal network followed by the gradual formation of a secondary micellar structure (∼12 nm). Such core–shell micellar architectures reinforced the hierarchical structure and endowed the hydrogel with thermoresponsiveness, verified by rheology and SAXS. Owing to the bioinspired phenolic chemistry, the CPF hydrogel was adhesive (binding strength 4–7 kPa) to artificial skin. Together with the rapid (<30 s) gelation kinetics, the hydrogel can be delivered by a dual-syringe as a fast adhesive. Moreover, the fast-gelled nature of the CPF hydrogel allowed spatially homogeneous embedding of mesenchymal stem cells that further developed into multicellular spheroids in 14 days. This new self-healing hydrogel shows multifunctionalities, benefiting from micellar architectures and phenolic modification. The corresponding hierarchical structure investigation provides an insight into the multiscale designs of a next-generation self-healing hydrogel for biomedical applications.

中文翻译：

---

具有分层胶束结构和快速粘合性的可注射酚醛-壳聚糖自愈水凝胶

可生物降解的自修复水凝胶是治疗系统、可重复使用的设备和智能细胞/药物载体非常理想的材料。许多研究工作都集中在通过物理或化学策略/设计的自修复水凝胶的附加功能上。其中，N合成-[3-(4-羟基苯基)丙酰胺基]壳聚糖和双功能Pluronic-F127交联剂(DF-PF)并反应形成高含水量(96.5 wt%)的酚醛-壳聚糖自修复水凝胶(CPF) ）。水凝胶的相干小角 X 射线散射（SAXS）分析揭示了快速形成的初级分形网络，随后逐渐形成二级胶束结构（~12 nm）。通过流变学和 SAXS 验证，这种核-壳胶束结构增强了层次结构并使水凝胶具有热响应性。由于受生物启发的酚类化学，CPF 水凝胶与人造皮肤具有粘性（结合强度 4-7 kPa）。连同快速 (<30 s) 凝胶化动力学，水凝胶可以通过双注射器作为快速粘合剂输送。而且，CPF 水凝胶的快速凝胶性质允许间充质干细胞在空间上均匀嵌入，这些干细胞在 14 天内进一步发展成多细胞球体。这种新型自修复水凝胶显示出多功能性，受益于胶束结构和酚类改性。相应的层次结构研究提供了对用于生物医学应用的下一代自修复水凝胶的多尺度设计的深入了解。