A viscoelastic alginate-based hydrogel network coordinated with spermidine for periodontal ligament regeneration

Periodontitis can cause irreversible defects in the periodontal ligament (PDL), the regeneration of which is the major obstacle to the clinical treatment of periodontitis. Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration. However, existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium, which may have been shown as an important role in tissue regeneration. Meanwhile, the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive. In this study, we developed a bi-crosslinking viscoelastic hydrogel (Alg-PBA/Spd) by integrating phenylboronic acid-modified alginate with anti-inflammatory agent (spermidine) through borate ester and B-N coordination bonds, where spermidine will be released with the degradation of the hydrogel. Alg-PBA/Spd hydrogel is biocompatible, injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking. We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage. Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.