Programmatic regulation of macrophage polarization by HAp@MXene nanocomposites to promote bone repair

Laisen Cui; Haina Huang; Yubo Zheng; Jiahao Zhang; Han Hai; Kai Bian; Zhichao Feng; Nik Ahmad Nizam Nik Malek; Wan Hairul Anuar Kamaruddin; Shan Lu; Bojun Xie; Ke Gao; Benjie Wei; Ya Liu; Chunhui Sun; Hong Liu; Chao Liu

doi:10.1002/bmm2.70034

BMEMat ›› 2026, Vol. 4 ›› Issue (1) :e70034 DOI: 10.1002/bmm2.70034

RESEARCH ARTICLE

Programmatic regulation of macrophage polarization by HAp@MXene nanocomposites to promote bone repair

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¹. Institute for Advanced Interdisciplinary Research (IAIR), University of Jinan, Jinan, China

². Department of Oral and Maxillofacial Surgery, Qilu Hospital, Institute of Stomatology, Shandong University, Jinan, China

³. Cheeloo College of Medicine, Shandong University, Jinan, China

⁴. Centre for Sustainable Nanomaterials (CSNano), Ibnu Sina Institute for Scientific and Industrial Research (ISI-ISIR), Universiti Teknologi Malaysia, Johor Bahru, Malaysia

⁵. Pusat Pengurusan Makmal Universiti, Universiti Teknologi Malaysia, Johor Bahru, Malaysia

⁶. State Key Laboratory of Crystal Materials, Shandong University, Jinan, China

⁷. College of Marine Life Science, Ocean University of China, Qingdao, China

⁸. Department of Stomatology, Qilu Hospital of Shandong University Dezhou Hospital & Dezhou Municipal Clinical Research Center for Oral Diseases, Dezhou, China

yaliu@ouc.edu.cn

ifc_sunch@ujn.edu.cn

hongliu@sdu.edu.cn

qiluliuchao@sdu.edu.cn

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Abstract

Patients with large-area bone defects are highly prone to infection, which significantly hinders healing. This study presents an innovative strategy that combines exogenous physical signals with implantable materials to achieve programmed immune modulation by dynamically regulating macrophage M1/M2 polarization, striking a balance between antibacterial activity and bone regeneration. Specifically, we synthesized HAp@MXene nanocomposites by integrating hydroxyapatite nanorods with MXene nanosheets, resulting in multifunctional materials with unique magnetoelectric properties and controlled Ca²⁺ release. These nanocomposites exert their effects through cellular internalization, where magnetoelectric induction generates intracellular currents to promote macrophage M1 polarization, initiating a pro-inflammatory response to mitigate infection risk. Subsequently, calcium ions are released within lysosomes, driving macrophage M2 polarization to facilitate anti-inflammatory response and promote tissue regeneration. This dual-modality mechanism achieves the precise programmatic regulation of macrophages, accelerates and optimizes the process of bone defect repair, and underscores the immense potential of HAp@MXene nanocomposites in synergistic antibacterial and bone regeneration therapies.

Keywords

bone regeneration / electrical stimulation / hydroxyapatite / macrophage polarization / MXene / programmatic regulation

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Laisen Cui, Haina Huang, Yubo Zheng, Jiahao Zhang, Han Hai, Kai Bian, Zhichao Feng, Nik Ahmad Nizam Nik Malek, Wan Hairul Anuar Kamaruddin, Shan Lu, Bojun Xie, Ke Gao, Benjie Wei, Ya Liu, Chunhui Sun, Hong Liu, Chao Liu. Programmatic regulation of macrophage polarization by HAp@MXene nanocomposites to promote bone repair. BMEMat, 2026, 4 (1) : e70034 DOI:10.1002/bmm2.70034

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