From crosslinking strategies to biomedical applications of hyaluronic acid-based hydrogels: A review

Hyaluronic acid (HA) is not only a natural anionic polysaccharide with excellent biocompatibility, biodegradability, and moisturizing effect, but also an essential factor that can affect angiogenesis, inflammation, cell behavior, which has a wide range of applications in the biomedical field. Among them, HA-based hydrogels formed by various physical or chemical crosslinking strategies are particularly striking. They not only retain the physiological function of HA, but also have the skeleton function of hydrogel, which further expands the application of HA. However, HA-based natural hydrogels generally have problems such as insufficient mechanical strength and susceptibility to degradation by hyaluronidase, which limits their application to a certain extent. To solve such problems, researchers have prepared a variety of HA-based multifunctional hydrogels with remarkable properties in recent years by adopting various structural modification methods or novel crosslinking strategies, as well as introducing functionally reactive molecules or moieties, which have extended the application scope. This manuscript systematically introduced common crosslinking strategies of HA-based hydrogels and highlighted the development of novel HA-based hydrogels in anticancer drug delivery, cartilage repair, three-dimensional cell culture, skin dressing and other fields. We hope to provide some references for the subsequent development of HA-based hydrogels in the biomedical field.