Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis
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ARTICLE
Cite as Nano-Micro Lett. (2021) 13:28 Received: 9 June 2020 Accepted: 28 September 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-00540-z
Dual‑Wavelength Photosensitive Nano‑in‑Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis Qin Zhao1, Miusi Shi1, Chengcheng Yin1, Zifan Zhao1, Jinglun Zhang1, Jinyang Wang1, Kailun Shen1, Lingling Zhang1,2, Hua Tang3, Yin Xiao4, Yufeng Zhang1,2 *
HIGHLIGHTS • The controlled release of IL-4 and dexamethasone by a dual-wavelength photosensitive nano-in-micro scaffold (biphasic calcium phosphate loaded with goad nanocage, BCP-GNC) enables the regulation of specific immune cells and immune responses. • BCP-GNC regulates innate and adaptive immune responses in two stages (directing the M2 polarization of macrophages and inhibiting the maturation of dendritic cells) to promote osteoinduction.
ABSTRACT The immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote
New bone formation
regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accu-
Early stage
rately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to
Late stage
target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific
M1 macrophage
M2 macrophage
Immature DC
Mature DC
regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis. KEYWORDS Gold nanocage; Drug release; Photocatalysis; Immunomodulation; Osteoinduction * Yufeng Zhang, [email protected] 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, People’s Republic of China 2 Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, People’s Republic of China 3 Institute of Immunology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, People’s Republic of China 4 Institute of Health and Biomedical Innovation & Australia‑China Centre for Tissue Engineering an
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