2. Academic Validation
  3. Cichoric acid-loaded hydroxyapatite nanorods remodel the immune microenvironment to enhance bone regeneration

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

  • Phytomedicine. 2025 Dec 12:150:157701. doi: 10.1016/j.phymed.2025.157701.
Xiaolong Lin 1,  Chenlong Liu 2,  Yuqing Lei 3,  Tao Ma 2,  Yuting Sun 2,  Jiapei Yao 2,  Tao Fu 4,  Haihua Zhu 1,  Dong Li 5,  Jingjing Shang 6,  Xindie Zhou 7
Affiliations

Affiliations

  • 1 Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.
  • 2 Department of Orthopedics, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, 213000, China.
  • 3 Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital, School of Biomedical Engineering Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
  • 4 Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, School of Stomatology, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, Zhejiang, 310006, China.
  • 5 Trauma Center, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, 213000, China. Electronic address: [email protected].
  • 6 Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, 213000, China. Electronic address: [email protected].
  • 7 Department of Orthopedics, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou, 213000, China; Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture, Qinghai 811800, China. Electronic address: [email protected].
PMID: 41421279 DOI: 10.1016/j.phymed.2025.157701
Abstract

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

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

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

Methods: 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.

Results: 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.

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

Keywords

Bone defect regeneration; Cichoric acid-loaded hydroxyapatite nanocomposite; Immunometabolic regulation; Macrophage polarization; Osteogenesis; Vascularized bone regeneration.

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