Injectable, pore-forming, self-healing, and adhesive hyaluronan hydrogels for soft tissue engineering applications

Abstract Most existing injectable hydrogels are non-porous, thereby lacking a microporous structure to promote cell ingrowth. Also, most hydrogels do not effectively adhere to the host tissue. The present study describes an injectable double network hydrogel formed by combining two hyaluronic acid (HA) derivatives, namely dopamine grafted HA (DAHA) and methacrylated HA (HAMA). These constituents instantly form a physically crosslinked network through Fe 3+ -dopamine coordination, and confer fast gelation, pore formation, and self-healing properties to the hydrogel. Photocroslinked upon UV exposure, HAMA forms a chemically crosslinked network, thereby improving mechanical and degradation properties. The adhesive properties of this hydrogel are attributed to the presence of dopamine groups, inspired by mussel creatures. Proper modification of HA chains was confirmed by NMR spectroscopy. The physical, mechanical, rheological, and biological properties of the new hydrogels were quantified in wet laboratory conditions. The results revealed that the DAHA/HAMA hydrogel rapidly forms a self-healing microporous adhesive scaffold with a 26.9 µm pore size, 29.4 kPa compressive modulus, and 12.8 kPa adhesion strength in under 6 s. These findings suggest that the new hydrogel is a promising candidate for in situ repair of soft tissues, particularly mechanically dynamic ones such as the vocal folds, cartilage, and dermis.