2025-03-26 シンガポール国立大学(NUS)
The microneedles were fabricated from poly lactic-co-glycolic acid (PLGA), an FDA-approved class of biodegradable polymers that are biocompatible and can be used in the sustained delivery of drugs and other molecules. The sponge-like PLGA microneedles, made using the moulds shown above, can help to alleviate inflammatory skin disorders.
<関連情報>
- https://news.nus.edu.sg/microneedle-technology-accelerate-diabetic-wound-healing/
- https://advanced.onlinelibrary.wiley.com/doi/10.1002/adfm.202402539
- https://www.sciencedirect.com/science/article/abs/pii/S0142961224002345
スポンジ状のマイクロニードルがケモカインを空間的に封じ込め、単球を減少させ、炎症性皮膚障害を緩和する Sponge-Like Microneedles Spatially Sequester Chemokines and Deplete Monocytes to Alleviate Inflammatory Skin Disorders
Zhicheng Le, Yufeng Shou, Renee R. Li, Ling Liu, Runcheng Tan, Christopher John Charles, Zhijia Liu, Yongming Chen, Andy Tay
Advanced Functional Materials Published: 24 July 2024
DOI:https://doi.org/10.1002/adfm.202402539
Abstract
Persistent 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.
生物活性スクラルファートをベースとしたマイクロニードルは、マクロファージの再プログラミングと内因性成長因子の保護を通じて創傷治癒を促進する Bioactive sucralfate-based microneedles promote wound healing through reprogramming macrophages and protecting endogenous growth factors
Zhicheng Le, Mayk Caldas Ramos, Yufeng Shou, Renee R. Li, Hong Sheng Cheng, Clarisse JM. Jang, Ling Liu, Chencheng Xue, Xianlei Li, Hong Liu, Chwee Teck Lim, Nguan Soon Tan, Andrew D. White, Christopher John Charlesj, Yongming Chen, Zhijia Liu, Andy Tay
Biomaterials Available online 4 July 2024
DOI:https://doi.org/10.1016/j.biomaterials.2024.122700
Abstract
Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound environments. Here, we present a two-stage strategy using bioactive sucralfate-based microneedle (SUC-MN) for delivering interleukin-4 (IL-4) to accelerate wound healing. In the first stage, SUC-MN synergistically enhanced the effect of IL-4 through more potent reprogramming of pro-regenerative M2-like macrophages via the JAK-STAT pathway to increase endogenous GF production. In the second stage, sucralfate binds to GFs and sterically disfavors protease degradation to increase bioavailability of GFs. The IL-4/SUC-MN technology accelerated wound healing by 56.6 % and 46.5 % in diabetic mice wounds and porcine wounds compared to their respective untreated controls. Overall, our findings highlight the innovative use of molecular simulations to identify bioactive ingredients and their incorporation into microneedles for promoting wound healing through multiple synergistic mechanisms.
