# Synthesis and evaluation of resveratrol–cerium modified hydroxyapatite for enhanced bone repair scaffolds

## TL;DR

A new bone repair scaffold was developed using resveratrol and cerium to improve healing with anti-inflammatory, antibacterial, and bone-growing properties.

## Contribution

A novel resveratrol–cerium modified hydroxyapatite composite was synthesized for bone repair scaffolds with combined anti-inflammatory, antibacterial, and osteogenic effects.

## Key findings

- The PCL@10Res–Ce/HA scaffold showed improved antibacterial activity and enhanced cell adhesion and proliferation.
- The scaffold upregulated Runx2 and BMP2 expression, promoting osteogenic differentiation and bone regeneration in vivo.
- The composite demonstrated anti-inflammatory properties and was confirmed safe for clinical use.

## Abstract

Metal-phenolic networks (MPNs) are a category of amorphous coordination network materials formed by metal ions and phenolic ligands. They can be integrated into matrix composites to significantly enhance the overall functionality of the composites. In this study, to leverage the anti-inflammatory, antibacterial, and osteogenic properties of resveratrol (Res) and cerium (Ce), an innovative Res–Ce MPN was synthesized to modify hydroxyapatite (HA) nanoparticles. These Res–Ce/HA nanoparticles were then blended with polycaprolactone (PCL) to fabricate 3D-printed bone repair scaffolds. The results showed that the composite scaffold containing 10% Res–Ce/HA nanoparticles (PCL@10Res–Ce/HA) exhibited improved antibacterial activity. In vitro experiments revealed that Res–Ce MPNs in the PCL@10Res–Ce/HA scaffold notably enhanced the adhesion and proliferation of MC3T3-E1 cells on the scaffold surface. Simultaneously, they upregulated the expression of Runx2 and BMP2, and thus facilitated the osteogenic differentiation of cells. Furthermore, in vivo rat tibial defect repair experiments demonstrated that the 3D-printed PCL@10Res–Ce/HA scaffold remarkably promoted osteogenesis by upregulating BMP2 expression. Additionally, Res–Ce MPNs in the PCL@10Res–Ce/HA scaffold inhibited excessive inflammation, thereby supporting bone regeneration. Importantly, comprehensive biosafety evaluations confirmed the clinical feasibility of the PCL@10Res–Ce/HA scaffold. Collectively, these findings indicate that the PCL@Res–Ce/HA scaffold with optimized composition integrates anti-inflammatory, immunomodulatory, and bone defect repair capabilities, making it a promising candidate material for bone defect repair.

PCL scaffolds incorporated with Res–Ce MPN-modified HA nanoparticles were prepared. They show synergistic antibacterial, anti-inflammatory, and osteogenic activities, effectively promoting bone defect repair with excellent biosafety.