PMID- 33576368 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210514 IS - 2047-4849 (Electronic) IS - 2047-4830 (Linking) VI - 9 IP - 7 DP - 2021 Apr 7 TI - A "sandwich" cell culture platform with NIR-responsive dynamic stiffness to modulate macrophage phenotypes. PG - 2553-2561 LID - 10.1039/d0bm02194f [doi] AB - Considering the key roles of macrophages in tissue repair and immune therapy, designing smart biomaterials able to harness macrophage phenotypes on demand during the healing process has become a promising strategy. Here, a novel "sandwich" cell culture platform with near-infrared (NIR) responsive dynamic stiffness was fabricated to polarize bone marrow-derived macrophages (BMDMs) in situ for revealing the relationship between the macrophage phenotype and substrate stiffness dynamically. Under NIR irradiation, calcium ions (Ca(2+)) diffused through the middle layer of the IR780-mixed phase change material (PCM) due to the photothermal effect of IR780, resulting in an increase of hydrogel stiffness in situ by the crosslinking of the upper layer of the hyaluronic acid-sodium alginate hydrogel (MA-HA&SA). The up-regulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) was quantified by immunostaining and enzyme-linked immune sorbent assay (ELISA), respectively, indicating the transformation of macrophages from the anti-inflammatory to pro-inflammatory phenotype under dynamic stiffness. The nuclear Yes-associated-protein (YAP) ratio positively correlated with the shift of the macrophage phenotype. The modulation of macrophage phenotypes by stiffness-rise without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate immune reactions to achieve optimized healing or therapeutic outcomes. FAU - Yuan, Peiqi AU - Yuan P AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. liema@zju.edu.cn. FAU - Luo, Yilun AU - Luo Y FAU - Luo, Yu AU - Luo Y FAU - Ma, Lie AU - Ma L LA - eng PT - Journal Article DEP - 20210212 PL - England TA - Biomater Sci JT - Biomaterials science JID - 101593571 RN - 0 (Hydrogels) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Cell Culture Techniques MH - Hydrogels MH - *Macrophages MH - Phenotype MH - *Tumor Necrosis Factor-alpha EDAT- 2021/02/13 06:00 MHDA- 2021/05/15 06:00 CRDT- 2021/02/12 08:40 PHST- 2021/02/13 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2021/02/12 08:40 [entrez] AID - 10.1039/d0bm02194f [doi] PST - ppublish SO - Biomater Sci. 2021 Apr 7;9(7):2553-2561. doi: 10.1039/d0bm02194f. Epub 2021 Feb 12.