Propolis and Hydroxyapatite Combination for Dentin Repair: Bioactivity, Target Prediction, and SAR Analysis

Preserving dental pulp vitality remains a critical challenge in restorative dentistry, particularly when managing deep carious lesions with potential pulpal exposure. In this study, a biofunctional approach is introduced by combining propolis, a natural resinous compound rich in bioactive flavonoids, with hydroxyapatite (HA), a bioceramic material known for its mineralization and osteoinductive properties. The aim is to develop a dual-function pulp capping system capable of both suppressing inflammation and promoting dentin regeneration. Using a structureâ activity relationship (SAR)-based prediction model, key compounds in propolis were identified to exhibit strong affinity for pro-inflammatory mediators such as TNF-α and IL-1β, while also modulating angiogenic factors like VEGFA. Hydroxyapatite enhances these effects by facilitating ionic and hydrogen bonding with functional groups of propolis, thereby improving the stability and delivery of these compounds at the pulpâ��dentin interface. Network pharmacology analysis further reveals the composite's multi-target potential, with regulatory effects across immune and regenerative pathways, including the NF-κB and TGF-β1 signaling cascades. This study demonstrates that the molecular synergy between HA and propolis supports a bioactive microenvironment conducive to pulp healing, with significant implications for the rational design of next-generation biomaterials for vital pulp therapy. © 2026 Kurniawati et al and 2026 the authors.