Topically-applied collagen-binding serum albumin-fused interleukin-4 modulates wound microenvironment in non-healing wounds

Non-healing wounds have a negative impact on quality of life and account for many cases of amputation and even early death among patients. Diabetic patients are the predominate population affected by these non-healing wounds. Despite the significant clinical demand, treatment with biologics has not...

Full description

Saved in:
Bibliographic Details
Published in:npj Regenerative medicine 2023-09, Vol.8 (1), p.49-13, Article 49
Main Authors: Lauterbach, Abigail L., Wallace, Rachel P., Alpar, Aaron T., Refvik, Kirsten C., Reda, Joseph W., Ishihara, Ako, Beckman, Taryn N., Slezak, Anna J., Mizukami, Yukari, Mansurov, Aslan, Gomes, Suzana, Ishihara, Jun, Hubbell, Jeffrey A.
Format: Article
Language:English
Subjects:
631/61/2035
631/61/51/2314
Angiogenesis
Biomaterials
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cytokines
Diabetes
Immunology
Regenerative Medicine/Tissue Engineering
Stem Cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Non-healing wounds have a negative impact on quality of life and account for many cases of amputation and even early death among patients. Diabetic patients are the predominate population affected by these non-healing wounds. Despite the significant clinical demand, treatment with biologics has not broadly impacted clinical care. Interleukin-4 (IL-4) is a potent modulator of the immune system, capable of skewing macrophages towards a pro-regeneration phenotype (M2) and promoting angiogenesis, but can be toxic after frequent administration and is limited by its short half-life and low bioavailability. Here, we demonstrate the design and characterization of an engineered recombinant interleukin-4 construct. We utilize this collagen-binding, serum albumin-fused IL-4 variant (CBD-SA-IL-4) delivered in a hyaluronic acid (HA)-based gel for localized application of IL-4 to dermal wounds in a type 2 diabetic mouse model known for poor healing as proof-of-concept for improved tissue repair. Our studies indicate that CBD-SA-IL-4 is retained within the wound and can modulate the wound microenvironment through induction of M2 macrophages and angiogenesis. CBD-SA-IL-4 treatment significantly accelerated wound healing compared to native IL-4 and HA vehicle treatment without inducing systemic side effects. This CBD-SA-IL-4 construct can address the underlying immune dysfunction present in the non-healing wound, leading to more effective tissue healing in the clinic.
ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-023-00326-y