What question did this study set out to answer?

The aim is to develop a composite scaffold that combines structural support and bioactivity to improve bone regeneration in critical-sized defects.

January 22, 2026

Immunomodulation and Oxidative Stress Mitigation Mediate Enhanced Bone Regeneration by a Platelet‐Rich Plasma‐Loaded Composite Scaffold

Key Points

The aim is to develop a composite scaffold that combines structural support and bioactivity to improve bone regeneration in critical-sized defects.
Developed a PRP-loaded PDA/CS hydrogel integrated into a 3D printed n-HA/PA66 scaffold.
Assessed cytoprotective and immunomodulatory effects in vitro using human osteoblasts and other cell types under stress conditions.
Validated the scaffold's efficacy in a rabbit femoral condyle model through various imaging and histological techniques.
Demonstrated antioxidant activity of the hydrogel, protecting cells from oxidative stress.
Enhanced BMSC proliferation and mineralization while promoting M2 macrophage polarization.
Significantly improved bone microarchitecture and mineral density as well as upregulated osteogenic markers in vivo.

Abstract

ABSTRACT Repairing critical‐sized bone defects remains a clinical challenge. Nano‐hydroxyapatite/polyamide 66 (n‐HA/PA66) offers excellent biocompatibility and mechanics but limited bioactivity. This study aims to develop a multifunctional composite scaffold to overcome this limitation. A platelet‐rich plasma (PRP)‐loaded polydopamine/chitosan (PDA/CS) hydrogel was integrated with a 3D‐printed porous n‐HA/PA66 scaffold (PRP‐PDA/CS‐n‐HA/PA66). Hydrogel's cytoprotective, immunomodulatory, and osteogenic effects were assessed in vitro using human osteoblasts, macrophages, and bone marrow mesenchymal stem cells (BMSCs) under hydrogen peroxide (H 2 O 2 )‐induced oxidative stress or lipopolysaccharide (LPS)‐induced inflammatory conditions. The osteogenic efficacy of the PRP‐PDA/CS‐n‐HA/PA66 composite scaffold was further validated in a rabbit femoral condyle critical‐sized defect model, assessed by micro‐computed tomography, histological staining, and immunohistochemistry. The PRP‐PDA/CS hydrogel demonstrated potent antioxidant activity, protected osteoblasts and BMSCs from H 2 O 2 ‐induced apoptosis and functional impairment, and promoted macrophage polarization toward the pro‐healing M2 phenotype. It significantly enhanced BMSCs' proliferation, osteogenic differentiation, and mineralization. These effects were associated with the upregulation of the nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 antioxidant pathway and suppression of the nuclear factor kappa‐B inflammatory pathway. In vivo, the PRP‐PDA/CS‐n‐HA/PA66 composite scaffold markedly accelerated new bone formation, improved bone microarchitecture, including bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density (BMD), upregulated osteogenic marker expression, and concurrently reduced local M1 macrophages, oxidative DNA damage, and pro‐inflammatory cytokines. In conclusion, the PRP‐PDA/CS‐n‐HA/PA66 composite scaffold synergizes structural support with multifaceted bioactivity, effectively promoting bone regeneration by mitigating oxidative stress, modulating immune responses, and enhancing osteogenesis, demonstrating significant translational potential.

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