State Key Laboratory in Quality Research of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China.
State Key Laboratory in Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.
Adv Mater. 2024 Feb;36(6):e2304655. doi: 10.1002/adma.202304655. Epub 2023 Dec 4.
Hair loss affects over 50 million people worldwide with limited therapeutic options. Despite evidence highlighting the vital role of local immune cells in regulating the life cycle of hair follicles (HFs), accurate regulation of immunocytes to directly promote hair growth remains unachieved. Here, inspired by the physiological feedback in the skin immunity to suppress microbe-triggered inflammation, an oligosaccharide biomaterial with "unmasked" specific activity is developed to recruit regulatory T (T ) cells around HFs, leading to accelerated hair growth in mice. By processing the glucomannan polysaccharide via controllable enzymatic cleavage, a series of oligosaccharide fractions with more specific chemokine-inducing functions is obtained. Notably, a hexasaccharide-based fraction (OG6) stimulates macrophages to selectively express T -chemoattractant C-C Motif Chemokine Ligand 5 (CCL5) through a mannose receptor-mediated endocytosis and NOD1/2-dependent signaling, as evidenced by molecular docking, inhibition assays, and a Foxp3-reporter mouse model. Intradermal delivery of OG6 to the depilated mouse skin promotes T mobilization around HFs and stimulates de novo regeneration of robust hairs. This study demonstrates that unmasking precise immunomodulatory functions in oligosaccharides from their parental polysaccharide can potentially solve the long-lasting dilemma with polysaccharide biomaterials that are widely renowned for versatile activities yet high heterogeneity, opening new avenues to designing glycan-based therapeutic tools with improved specificity and safety.
脱发影响着全球超过 5000 万人，而治疗选择却十分有限。尽管有证据表明局部免疫细胞在调节毛囊（HFs）生命周期方面起着至关重要的作用，但免疫细胞的精确调节以直接促进头发生长仍未实现。在这里，受皮肤免疫对微生物触发炎症的生理反馈的启发，开发了一种具有“去掩蔽”特定活性的寡糖生物材料，用于招募 HF 周围的调节性 T（T）细胞，从而加速小鼠的毛发生长。通过对葡甘露聚糖多糖进行可控酶切处理，获得了一系列具有更特异趋化因子诱导功能的寡糖片段。值得注意的是，一种基于六糖的片段（OG6）通过甘露糖受体介导的内吞作用和 NOD1/2 依赖性信号转导，选择性地刺激巨噬细胞表达 T 细胞趋化因子 C-C 基序趋化因子配体 5（CCL5），这一点得到了分子对接、抑制实验和 Foxp3 报告基因小鼠模型的证实。将 OG6 皮内递送至脱毛小鼠皮肤可促进 HF 周围 T 细胞的动员，并刺激新的强壮毛发再生。本研究表明，从多糖母体中揭示寡糖的精确免疫调节功能，可能有助于解决多糖生物材料长期存在的困境，这些材料以多功能性而闻名，但具有高度异质性，为设计基于聚糖的治疗工具开辟了新途径，提高了特异性和安全性。
