Zinc‐Modified Sulfonated Polyetheretherketone Surface with Immunomodulatory Function for Guiding Cell Fate and Bone Regeneration

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Abstract

The cytokines released by immune cells are considered important factors to induce bone tissue regeneration. However, the pathway of those bone‐targeting macrophage cytokines induced by biomaterial surface under tissue microenvironment is rarely reported. In this study, the immunomodulatory capability of zinc ions on macrophage polarization and its effects on osteogenic differentiation are investigated. Hence, a layer of zinc ions are incorporated on sulfonated polyetheretherketone (SPEEK) biomaterials by using a customized magnetron sputtering technique. The results reveal that the microenvironment on Zn‐coated SPEEK can modulate nonactivated macrophage polarization to an anti‐inflammatory phenotype and induce the secretion of anti‐inflammatory and osteogenic cytokines. The osteogenic differentiation capability of bone marrow stromal cells (BMSCs) is therefore enhanced, leading to improved osteointegration between the zinc‐coated SPEEK and bone tissue. This study verifies that zinc ion is a promising additive in the osteoimmunomodulation process and provides knowledge that may pave the way to develop the next generation of immunomodulatory biomaterials.

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Most cited references 4

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Recent research has brought about a clear understanding that successful fracture healing is based on carefully coordinated cross-talk between inflammatory and bone forming cells. In particular, the key role that macrophages play in the recruitment and regulation of the differentiation of mesenchymal stem cells (MSCs) during bone regeneration has been brought to focus. Indeed, animal studies have comprehensively demonstrated that fractures do not heal without the direct involvement of macrophages. Yet the exact mechanisms by which macrophages contribute to bone regeneration remain to be elucidated. Macrophage-derived paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles; however the relative importance of inflammatory (M1) and tissue regenerative (M2) macrophages in guiding MSC differentiation along the osteogenic pathway remains poorly understood. In this review, we summarize the current understanding of the interaction of macrophages and MSCs during bone regeneration, with the emphasis on the role of macrophages in regulating bone formation. The potential implications of aging to this cellular cross-talk are reviewed. Emerging treatment options to improve facture healing by utilizing or targeting MSC-macrophage crosstalk are also discussed.

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Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a "nanoengineered surface" for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties.

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Author and article information

Contributors

Kelvin W. K. Yeung: wkkyeung@hku.hk

Paul K. Chu: paul.chu@cityu.edu.hk

Xianlong Zhang: dr_zhangxianlong@163.com

Journal

Journal ID (nlm-ta): Adv Sci (Weinh)

Journal ID (iso-abbrev): Adv Sci (Weinh)

Journal ID (doi): 10.1002/(ISSN)2198-3844

Journal ID (publisher-id): ADVS

Title: Advanced Science

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2198-3844

Publication date (Electronic): 07 August 2018

Publication date Collection: October 2018

Volume: 5

Issue: 10 ( doiID: 10.1002/advs.v5.10 )

Electronic Location Identifier: 1800749

Affiliations

[ ¹ ] Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai Jiao Tong University Shanghai 200233 China

[ ² ] Department of Orthopaedics and Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong 999077 China

[ ³ ] Department of Physics and Department of Materials Science and Engineering City University of Hong Kong Tat Chee Avenue Kowloon Hong Kong 999077 China

Author notes

[*] [* ]E‐mail: wkkyeung@ 123456hku.hk , paul.chu@ 123456cityu.edu.hk , dr_zhangxianlong@ 123456163.com

Article

Publisher ID: ADVS761

DOI: 10.1002/advs.201800749

PMC ID: 6193167

PubMed ID: 30356934

SO-VID: 258a7c5d-10f9-4fd1-92bd-017b4e6787e4

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date received : 15 May 2018

Date revision received : 19 June 2018

Page count

Figures: 9, Tables: 0, Pages: 13, Words: 7743

Funding

Funded by: National Natural Science Foundation of China

Award ID: 81472109

Award ID: 81772309

Award ID: 81702126

Award ID: 31370957

Funded by: Research Grant Council General Research Funds

Award ID: CityU 11205617

Award ID: CityU 11301215

Award ID: HKU 718913

Award ID: N_HKU726‐16

Funded by: City University of Hong Kong Applied Research Grant

Award ID: 9667144

Funded by: Shanghai Jiao Tong University Medical‐Engineering Foundation, China

Award ID: YG2016MS14

Custom metadata

source-schema-version-number 2.0

component-id advs761

cover-date October 2018

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0.1 mode:remove_FC converted:18.10.2018

Zinc‐Modified Sulfonated Polyetheretherketone Surface with Immunomodulatory Function for Guiding Cell Fate and Bone Regeneration

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