Injectable Liposome-Loaded Hydrogel Formulations with Controlled Release of Curcumin and ?-Tocopherol for Dental Tissue Engineering

An injectable hydrogel formulation is developed utilizing low- and high-molecular-weight chitosan (LCH and HCH) incorporated with curcumin and alpha-tocopherol-loaded liposomes (Lip/Cur+Toc). Cur and Toc releases are delayed within the hydrogels. The injectability of hydrogels is proved via rheological analyses. In vitro studies are conducted using human dental pulp stem cells (hDPSCs) and human gingival fibroblasts (hGFs) to examine the biological performance of the hydrogels toward endodontics and periodontics, respectively. The viability of hDPSCs treated with the hydrogels with Lip/Cur+Toc is the highest till day 14, compared to the neat hydrogels. During odontogenic differentiation tests, alkaline phosphatase (ALP) enzyme activity of hDPSCs is induced in the Cur-containing groups. Biomineralization is enhanced mostly with Lip/Cur+Toc incorporation. The viability of hGFs is the highest in HCH combined with Lip/Cur+Toc while wound healing occurs almost 100% in both (Lip/Cur+Toc@LCH and Lip/Cur+Toc@HCH) after 2 days. Antioxidant activity of Lip/Cur+Toc@LCH on hGFs is significantly the highest among the groups. Antimicrobial tests demonstrate that Lip/Cur+Toc@LCH is more effective against Escherichia coli whereas so is Lip/Cur+Toc@HCH against Staphylococcus aureus. The antimicrobial mechanism of the hydrogels is investigated for the first time through various computational models. LCH and HCH loaded with Lip/Cur+Toc are promising candidates with multi-functional features for endodontics and periodontics.