Sponge‐Like Microneedles Spatially Sequester Chemokines and Deplete Monocytes to Alleviate Inflammatory Skin Disorders

Author:

Le Zhicheng12ORCID,Shou Yufeng1,Li Renee R.34,Liu Ling12,Tan Runcheng5,Charles Christopher John346,Liu Zhijia5,Chen Yongming5,Tay Andy127ORCID

Affiliation:

1. Department of Biomedical Engineering National University of Singapore Singapore 117583 Singapore

2. Institute of Health Innovation & Technology National University of Singapore Singapore 117599 Singapore

3. Department of Surgery Yong Loo Lin School of Medicine National University of Singapore Singapore 119077 Singapore

4. Cardiovascular Research Institute National University Heart Centre Singapore Singapore 119228 Singapore

5. School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education Sun Yat‐sen University Guangzhou 510006 China

6. Christchurch Heart Institute Department of Medicine University of Otago Christchurch 8001 New Zealand

7. NUS Tissue Engineering Program National University of Singapore Singapore 117510 Singapore

Abstract

AbstractPersistent inflammation, characterized by the intense interplay of inflammatory chemokine secretion and immune cell infiltration, is a hallmark of many skin disorders including diabetic wounds and psoriasis with inadequate therapeutic interventions. Monocyte chemotactic protein‐1 (MCP‐1) is an inflammatory chemokine that plays a key role in recruiting and polarizing monocytes into pro‐inflammatory macrophages to establish a vicious cycle that worsens the inflamed tissue microenvironment. Here, the sponge‐like microneedles (HPMN) technology is described to alleviate inflammatory skin disorders. Heparin/4‐arm PEG‐NH2 network crosslinked onto microneedle surface spatially attracted and sequestered multiple inflammatory chemokines including MCP‐1. Enrichment of MCP‐1 on microneedles recruits and traps inflammatory monocytes within the porous structure of microneedles. Subsequent removal of microneedles not only depletes inflammatory chemokine, MCP‐1, but also its cellular source. As a result, HPMN treatment facilitates 47.1% smaller open wound area in mice and 27.2% shorter wound length in pigs. To demonstrate the versatility of the HPMN technology, it is also shown that combining the method with standard‐of‐care immunosuppressants reduces 45.1% epidermis thickening and attenuated immune cell influx in a mouse psoriasis model. Overall, the HPMN technology is a novel demonstration of employing inflammatory chemokine and cell extraction to treat a broad range of inflammatory skin disorders.

Publisher

Wiley

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