Silk Fibroin Scaffold Architecture Regulates Inflammatory Responses and Engraftment of Bone Marrow-Mononuclear Cells

Nianji Yang; Matthew J Moore; Praveesuda L Michael; Miguel Santos; Yuen Ting Lam; Shisan Bao; Martin K C Ng; Jelena Rnjak-Kovacina; Richard P Tan; Steven G Wise

doi:10.1002/adhm.202100615

Silk Fibroin Scaffold Architecture Regulates Inflammatory Responses and Engraftment of Bone Marrow-Mononuclear Cells

Adv Healthc Mater. 2021 Aug;10(16):e2100615. doi: 10.1002/adhm.202100615. Epub 2021 May 7.

Authors

Nianji Yang^{1

2}, Matthew J Moore^{1

2}, Praveesuda L Michael^{1

2}, Miguel Santos^{1

2}, Yuen Ting Lam^{1

2}, Shisan Bao^{1

2}, Martin K C Ng^{3

4}, Jelena Rnjak-Kovacina⁵, Richard P Tan^{1

2}, Steven G Wise^{1

2

6}

Affiliations

¹ School of Medical Sciences, Faculty of Health and Medicine, The University of Sydney, Sydney, NSW, 2006, Australia.
² Charles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
³ Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
⁴ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, 2042, Australia.
⁵ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
⁶ The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Sydney, NSW, 2006, Australia.

PMID: 33963682
DOI: 10.1002/adhm.202100615

Abstract

Despite being one of the most clinically trialed cell therapies, bone marrow-mononuclear cell (BM-MNC) infusion has largely failed to fulfill its clinical promise. Implanting biomimetic scaffolds at sites of injury prior to BM-MNC infusion is a promising approach to enhance BM-MNC engraftment and therapeutic function. Here, it is demonstrated that scaffold architecture can be leveraged to regulate the immune responses that drive BM-MNC engraftment. Silk scaffolds with thin fibers and low porosity (LP) impairs immune activation in vitro compared with thicker fiber, high porosity (HP) scaffolds. Using the authors' established in vivo bioluminescent BM-MNC tracking model, they showed that BM-MNCs home to and engraft in greater numbers in HP scaffolds over 14 days. Histological analysis reveals thicker fibrous capsule formation, with enhanced collagen deposition in HP compared to LP scaffolds consistent with substantially more native CD68⁺ macrophages and CD4⁺ T cells, driven by their elevated pro-inflammatory M1 and Th1 phenotypes, respectively. These results suggest that implant architecture impacts local inflammation that drives differential engraftment and remodeling behavior of infused BM-MNC. These findings inform the future design of biomimetic scaffolds that may better enhance the clinical effectiveness of BM-MNC infusion therapy.

Keywords: biophysical cues; bone marrow mononuclear cells; electrospinning; inflammation; silk fibroin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Marrow
Bone Marrow Cells
Cell- and Tissue-Based Therapy
Fibroins*
Humans
Silk

Substances

Silk
Fibroins