Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks

TLDR

Hyaluronic acid, a versatile, biocompatible, biodegradable, non‑immunogenic component of the extracellular matrix, is widely employed to fabricate hydrogels with tunable morphology, stiffness, and bioactivity, ranging from macroscopic networks to micro‑ and nanogels with complex architectures, anisotropy, and hierarchical structures that support cellular functions. The review aims to highlight recent efforts to convert hyaluronic acid into drug‑releasing hydrogel particles and assemble them into complex, instructive macroscopic networks. These efforts involve transforming the polysaccharide into drug‑releasing hydrogel particles and integrating them into hybrid networks that provide spatial and temporal presentation of biological cues. HA‑based hydrogels show promise for tissue repair and regeneration.

Abstract

Hyaluronic acid (HA) is one of nature's most versatile and fascinating macromolecules. Being an essential component of the natural extracellular matrix (ECM), HA plays an important role in a variety of biological processes. Inherently biocompatible, biodegradable and non-immunogenic, HA is an attractive starting material for the construction of hydrogels with desired morphology, stiffness and bioactivity. While the interconnected network extends to the macroscopic level in HA bulk gels, HA hydrogel particles (HGPs, microgels or nanogels) confine the network to microscopic dimensions. Taking advantage of various scaffold fabrication techniques, HA hydrogels with complex architecture, unique anisotropy, tunable viscoelasticity and desired biologic outcomes have been synthesized and characterized. Physical entrapment and covalent integration of hydrogel particles in a secondary HA network give rise to hybrid networks that are hierarchically structured and mechanically robust, and capable of mediating cellular activities through the spatial and temporal presentation of biological cues. This review highlights recent efforts in converting a naturally occurring polysaccharide to drug releasing hydrogel particles, and finally, complex and instructive macroscopic networks. HA-based hydrogels are promising materials for tissue repair and regeneration.