Osteo-Immunomodulatory Role of Interleukin-4-Immobilized Plasma Immersion Ion Implantation Membranes for Bone Regeneration

Fei Wei; Yuqing Mu; Richard P Tan; Steven G Wise; Marcela M Bilek; Yinghong Zhou; Yin Xiao

doi:10.1021/acsami.2c17005

Osteo-Immunomodulatory Role of Interleukin-4-Immobilized Plasma Immersion Ion Implantation Membranes for Bone Regeneration

ACS Appl Mater Interfaces. 2023 Jan 18;15(2):2590-2601. doi: 10.1021/acsami.2c17005. Epub 2023 Jan 6.

Authors

Fei Wei^{1

2}, Yuqing Mu^{1

3

2}, Richard P Tan^{4

5}, Steven G Wise^{4

5

6}, Marcela M Bilek^{5

6

7

8}, Yinghong Zhou^{1

3

2}, Yin Xiao^{1

2

9}

Affiliations

¹ School of Mechanical, Medical and Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
² The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Brisbane, Queensland 4000, Australia.
³ School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, Queensland 4006, Australia.
⁴ School of Medical Sciences, Faculty of Health and Medicine, The University of Sydney, Camperdown, New South Wales 2006, Australia.
⁵ Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales 2006, Australia.
⁶ Sydney Nano Institute, The University of Sydney, Camperdown, New South Wales 2006, Australia.
⁷ School of Physics, The University of Sydney, Camperdown, New South Wales 2006, Australia.
⁸ School of Biomedical Engineering, The University of Sydney, Camperdown, New South Wales 2006, Australia.
⁹ School of Medicine and Dentistry, Griffith University, Southport, Queensland 4222, Australia.

PMID: 36607242
DOI: 10.1021/acsami.2c17005

Abstract

Barrier membranes for guided tissue regeneration are essential for bone repair and regeneration. The implanted membranes may trigger early inflammatory responses as a foreign material, which can affect the recruitment and differentiation of bone cells during tissue regeneration. The purpose of this study was to determine whether immobilizing interleukin 4 (IL4) on plasma immersion ion implantation (PIII)-activated surfaces may alter the osteo-immunoregulatory characteristics of the membranes and produce pro-osteogenic effects. In order to immobilize IL4, polycaprolactone surfaces were modified using the PIII technology. No discernible alterations were found between the morphology before and after PIII treatment or IL4 immobilization. IL4-immobilized PIII surfaces polarized macrophages to an M2 phenotype and mitigated inflammatory cytokine production under lipopolysaccharide stimulation. Interestingly, the co-culture of macrophages (on IL4-immobilized PIII surfaces) and bone marrow-derived mesenchymal stromal cells enhanced the production of angiogenic and osteogenic factors and triggered autophagy activation. Exosomes produced by PIII + IL4-stimulated macrophages were also found to play a role in osteoblast differentiation. In conclusion, the osteo-immunoregulatory properties of bone materials can be modified by PIII-assisted IL4 immobilization, creating a favorable osteoimmune milieu for bone regeneration.

Keywords: bone regeneration; macrophages; osteogenesis; plasma immersion ion implantation (PIII); surface modification.

MeSH terms

Bone Regeneration / physiology
Guided Tissue Regeneration* / methods
Immunologic Factors / chemistry
Immunologic Factors / pharmacology
Interleukin-4* / chemistry
Interleukin-4* / pharmacology
Membranes, Artificial
Osteogenesis / physiology

Substances

Interleukin-4
Immunologic Factors
Membranes, Artificial