Prediction of Secretome Release from Hydrogels Based on Molecular Interactions and Binding Affinity to Promoting Bone Regeneration in Periodontitis

Periodontitis causes irreversible alveolar bone resorption. Therefore, bone regeneration therapy is needed. Cell-free based regenerative therapy using secretome stem cells from exfoliated human deciduous teeth (SHED) containing growth factors, including TGF-β, FGF-2, and VEGF, can potentially increase the bone regeneration processes through angiogenesis and osteogenesis. Hydrogels made from chitosan (CS)/Beta-glycerophosphate (β-GP)/Hydroxyapatite (HA) can function as adhesives and control the release of bioactive contained in the secretome. This study aims to predict the role of the release of the secretome in the bone regeneration process through the binding interaction and release rate of TGF-β, FGF-2, and VEGF proteins with the compounds that make up CS/β-GP/ HA hydrogel through molecular docking. Three-dimensional (3D) structures for compounds and proteins obtained from the PubChem database. Docking analysis was carried out using Pyrx v.0.8 software. The molecular docking methods are used to identify bond positions and bond energies between proteins and chemical compounds. The results of molecular docking predictions for the interaction of TGF-β, FGF-2, and VEGF binding to the CS/β-GP/HA hydrogel constituent compounds indicated that interaction could block binding with their receptors. The most ligand interactions are found in TGF-β with CS/BGP/HA on five amino acids, namely Trp32, His34, Try91, Arg25, and His40. FGF-2 and VEGF are each bound to one amino acid, namely Asn102 with CS and Glu64 with HA. From the results of the binding affinity analysis, it is known that TGF-β has the strongest total binding affinity, namely -17.0 kcal/mol, followed by VEGF and FGF-2, which have total binding affinities of -15.3 kcal/mol and -13.7 kcal. It concluded that the controlled release of the SHED secretome from the CS/β-GP/HA hydrogel base begins with the release of FGF-2 and VEGF for angiogenesis, followed by the release of TGF-β for osteogenesis that has the potential to increase the bone regeneration in periodontitis.