Cichoric acid-loaded hydroxyapatite nanorods remodel the immune microenvironment to enhance bone regeneration

Bone defect regeneration requires both osteogenic stimulation and immunomodulation of the local microenvironment.

This study aimed to develop a cichoric acid-loaded hydroxyapatite nanocomposite (CA@HAp) that integrates metabolic and immunological regulation to promote bone repair.

The efficacy of CA@HAp was evaluated in a rat femoral defect model.

Cichoric acid (CA) was electrostatically adsorbed onto nano-hydroxyapatite to form CA@HAp, which exhibited stable properties and pH-dependent release. Its effects on macrophage metabolism, polarization, cytokine secretion, and osteogenic signal expression were analyzed.

CA@HAp effectively reprogrammed macrophage metabolism, shifting polarization from pro-inflammatory M1 to pro-regenerative M2. This transition suppressed inflammatory cytokines (IL-12, IL-6, NLRP3) and upregulated anti-inflammatory and osteogenic factors (IκBα, BMP2, OPN, OCN, RUNX2). Furthermore, CA@HAp promoted angiogenesis and significantly enhanced osteogenesis, bone mineral density, and vascularized bone regeneration compared to control groups.

CA@HAp serves as a multifunctional immuno-osteogenic platform that couples metabolic reprogramming with macrophage polarization, presenting a promising strategy for bone defect regeneration.