Electroconductive gelatin/hyaluronic acid/hydroxyapatite scaffolds for enhanced cell proliferation and osteogenic differentiation in bone tissue engineering

Addressing the challenge of bone tissue regeneration requires creating an optimal microenvironment that promotes both osteogenesis and angiogenesis. Electroconductive scaffolds have emerged as promising solutions for bone regeneration; however, existing conductive polymers often lack biofunctionality and biocompatibility. In this study, we synthesized poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) using chemical oxidation polymerization and incorporated them into gelatin/hyaluronic acid/hydroxyapatite (Gel:HA:HAp) scaffolds to develop Gel:HA:HAp:PEDOT-NP scaffolds. Morphological analysis by scanning electron microscopy (SEM) showed a honeycomb-like structure with pores of 228-250 μm in diameter. The addition of the synthesized PEDOT NPs increased the conductive capabilities of the scaffolds to 1 × 10^-6 ± 1.3 × 10^-7 S/cm. Biological assessment of PEDOT NP scaffolds using human foetal osteoblastic 1.19 cells (hFOB), and human bone marrow-derived mesenchymal stem cells (hBMSCs) revealed enhanced cell proliferation and viability compared to control scaffold without NPs, along with increased osteogenic differentiation, evidenced by higher levels of alkaline phosphatase activity, osteopontin (OPN), alkaline phosphatase (ALP), and osteocalcin (OCN) expression, as observed through immunofluorescence, and enhanced expression of osteogenic-related genes. The conductive scaffold shows interesting mineralization capacity, as shown by Alizarin red and Osteoimage staining. Furthermore, PEDOT-NP scaffolds promoted angiogenesis, as indicated by improved tube formation abilities of human umbilical vein endothelial cells (HUVECs), especially at the higher concentrations of NPs. Overall, our findings demonstrate that the integration of PEDOT NPs scaffold enhances their conductive properties and promotes cell proliferation, osteogenic differentiation, and angiogenesis. Gel:HA:HAp:PEDOT-NP scaffolds exhibit promising potential as efficient biomaterials for bone tissue regeneration, offering a potential engineered platform for clinical applications.