Divergent immune responses to synthetic and biological scaffolds

Kaitlyn Sadtler; Matthew T Wolf; Sudipto Ganguly; Christopher A Moad; Liam Chung; Shoumyo Majumdar; Franck Housseau; Drew M Pardoll; Jennifer H Elisseeff

doi:10.1016/j.biomaterials.2018.11.002

Divergent immune responses to synthetic and biological scaffolds

Biomaterials. 2019 Feb:192:405-415. doi: 10.1016/j.biomaterials.2018.11.002. Epub 2018 Nov 9.

Authors

Kaitlyn Sadtler¹, Matthew T Wolf², Sudipto Ganguly³, Christopher A Moad², Liam Chung⁴, Shoumyo Majumdar⁵, Franck Housseau³, Drew M Pardoll³, Jennifer H Elisseeff⁶

Affiliations

¹ David H. Koch Institute for Integrative Cancer Research, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Anesthesia and Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston MA 02115, USA.
² Translational Tissue Engineering Center, Wilmer Eye Institute, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
³ Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
⁴ Translational Tissue Engineering Center, Wilmer Eye Institute, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
⁵ Translational Tissue Engineering Center, Wilmer Eye Institute, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
⁶ Translational Tissue Engineering Center, Wilmer Eye Institute, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: jhe@jhu.edu.

PMID: 30500722
DOI: 10.1016/j.biomaterials.2018.11.002

Abstract

The immune system plays a critical role in wound healing and the response to biomaterials. Biomaterials-directed regenerative immunology is an immunoengineering strategy that targets the immune system to promote tissue repair. Biomaterial scaffolds employed in regenerative medicine can be broadly classified as biological (such as those derived from the tissue extracellular matrix) or synthetic. Here, we show in depth the divergent myeloid response to biological versus synthetic biomaterial scaffolds. While neutrophil depletion and changes in physical properties such as shape and mechanics can modulate the pro-inflammatory myeloid immune response to synthetic materials to a degree, the overall general divergent myeloid responses persist. Biologic scaffolds elicit a type-2-like immune response with upregulation of genes such as Il4, Cd163, Mrc1 and Chil3, as well as genes associated with damage-associated molecular patterns providing another possible mechanism by which ECM scaffolds promote wound healing via amplification of endogenous wound-associated signaling pathways. Synthetic materials recruit a high proportion of neutrophils which is compounded by material stiffness and by the presence of an injury. Understanding the complex immune response to biomaterial classes will help in the efficient design of immunoengineering strategies and optimizing regenerative and reducing foreign body fibrotic responses to scaffolds.

Keywords: Immunology; Macrophages; Regenerative medicine; T cells; Tissue engineering.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biocompatible Materials / adverse effects*
Biocompatible Materials / chemistry
Female
Immunity
Inflammation / etiology*
Inflammation / immunology
Macrophages / immunology*
Mice, Inbred C57BL
Tissue Scaffolds / adverse effects*
Tissue Scaffolds / chemistry

Substances

Biocompatible Materials

Grants and funding

F32 EB025688/EB/NIBIB NIH HHS/United States