Construction and bone regeneration study of chitosan/F127 composite hydrogels encapsulating mesoporous polydopamine nanoparticles loaded with EGCG

Background　Bone defect repair is a common challenge in clinical orthopedics, and traditional repair materials are limited by drawbacks such as low biological activity and poor drug controlled-release performance. Objective　To construct a composite hydrogel capable of promoting bone defect repair by combining the properties of epigallocatechin gallate (EGCG) and mesoporous polydopamine (MPDA), while leveraging the excellent biocompatibility and mechanical properties of chitosan/F127 hydrogel. Methods　Cells treated with regular culture medium were used as the control (control group, Ctrl group). EGCG-loaded MPDA (MPDA@EGCG) nanoparticles were prepared, and their particle size, Zeta potential, and morphology were characterized using scanning electron microscopy (SEM) and a nanoparticle size and Zeta potential analyzer. Subsequently, the aforementioned nanoparticles were incorporated into chitosan/F127 hydrogel to fabricate the composite hydrogel (MPDA@EGCG-CF). The morphology, rheological properties, in vitro release behavior, biosafety, and in vitro osteogenic capacity of the composite hydrogel were evaluated via SEM, a rheometer, the CCK-8 assay, live/dead cell staining, hemolysis test, alkaline phosphatase staining with quantitative analysis, alizarin red staining with quantitative analysis, and Western blot analysis. Results　The MPDA@EGCG-CF hydrogel was successfully constructed. In vitro release studies demonstrated that the composite hydrogel could achieve sustained local release of EGCG for more than one week. Morphological observations via SEM revealed that the hydrogel exhibited favorable morphological characteristics with a porous structure. Cell experiments and hemolysis test confirmed the good biosafety of the composite material. Results from ALP staining, alizarin red staining, and Western blot analysis indicated that, compared with the control (Ctrl) group and the hydrogel group encapsulating non-drug-loaded MPDA, the MPDA@EGCG-CF hydrogel displayed significantly enhanced in vitro osteogenic differentiation capacity (P＜0.05). Conclusion　The constructed osteoconductive chitosan/F127 composite hydrogel encapsulating EGCG-loaded MPDA can realize long-term local release of EGCG and remarkably promote osteogenic differentiation in vitro, exhibiting promising application potential for bone regeneration.