Fabrication of an exosome-loaded thermosensitive chitin-based hydrogel for dental pulp regeneration

Injective thermosensitive hydrogels are considered promising scaffolds to trigger dental pulp regeneration in devitalized human teeth. In this study, we developed a hydroxypropyl chitin (HPCH)/chitin whisker (CW) thermosensitive hydrogel with enhanced mechanical properties and biological activities. Exosomes can serve as biomimetic tools for tissue engineering, but the rapid clearance of unconjugated exosomes in vivo limits their therapeutic effects. To address this challenge, exosomes were isolated from human pulp stem cells (hDPSCs) and directly embedded into the HPCH/CW pre-gel to form an exosome-loaded hydrogel (HPCH/CW/Exo). The exosome-loaded thermosensitive hydrogel can be easily injected into an irregular endodontic space and gelated in situ. In vitro cell experiments proved that the delivery of exosomes significantly improved the ability of hydrogels to promote odontogenesis and angiogenesis. Meanwhile, in vivo animal experiments revealed the formation of new dental pulp-like tissues in an implanted tooth root model. Therefore, the proposed hydrogel provides a great potential alternative to traditional root canal therapy in dental clinics.