Dual effect of curcumin/BMP-2 loaded in HA/PLL hydrogels on osteogenesis in vitro and in vivo

In the present study, we evaluated the potential of poly-L-lysine/hyaluronic acid (HA/PLL) hydrogels containing curcumin (CUR) and bone morphogenetic protein-2 (BMP-2) as bone tissue regeneration scaffolds. Hydrogels HP-1-2 were formed by amide bonds via the condensation reactions between 0.02 μmol HA and 0.06-0.12 μmol poly-L-lysine·hydrobromide (PLL·HBr). Physical, chemical, and thermal analyses revealed that the amount of PLL·HBr significantly influenced hydrogel properties. Based on an in vitro MG-63 cell proliferation test, HP-1-2 were cytocompatible, and all hydrogels containing different amounts of CUR and BMP-2, except for HA_0.02/PLL_0.06/CUR₂₀/BMP-2₁₀₀ (HPCB-4), resulted in cell proliferation above 80%. An in vitro release test showed that CUR and BMP-2 were consistently released from HA_0.02/PLL_0.06/CUR₁₅ (HPC), HA_0.02/PLL_0.06/BMP-2₁₀₀ (HPB), HA_0.02/PLL_0.06/CUR₁₅/BMP-2_{10.50, or 100} (HPCB-1-3), and HA_0.02/PLL_0.06/ CUR_{10 or 20}/BMP-2₁₀₀ (HPCB-4-5) for 7 and 28 days, respectively. In vitro ALP activity and calcium deposition and in vivo micro-computed tomography (micro-CT) tests demonstrated the potential application of HPCB-3 as bone tissue regeneration scaffolds, suggesting that bone tissue regeneration can be optimized by controlling the amounts of CUR and BMP-2.