Rational design of viscoelastic hydrogels for periodontal ligament remodeling and repair

The periodontal ligament (PDL) is a distinctive yet critical connective tissue vital for maintaining the integrity and functionality of tooth-supporting structures. However, PDL repair poses significant challenges due to the complexity of its mechanical microenvironment encompassing hard-soft-hard tissues, with the viscoelastic properties of the PDL being of particular interest. This review delves into the significant role of viscoelastic hydrogels in PDL regeneration, underscoring their utility in simulating biomimetic three-dimensional microenvironments. We review the intricate relationship between PDL and viscoelastic mechanical properties, emphasizing the role of tissue viscoelasticity in maintaining mechanical functionality. Moreover, we summarize the techniques for characterizing PDL's viscoelastic behavior. From a chemical bonding perspective, we explore various crosslinking methods and characteristics of viscoelastic hydrogels, along with engineering strategies to construct viscoelastic cell microenvironments. We present a detailed analysis of the influence of the viscoelastic microenvironment on cellular mechanobiological behavior and fate. Furthermore, we review the applications of diverse viscoelastic hydrogels in PDL repair and address current challenges in the field of viscoelastic tissue repair. Lastly, we propose future directions for the development of innovative hydrogels that will facilitate not only PDL but also systemic ligament tissue repair.