A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model
A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model
复制标题
3D 打印的 PRP-GelMA 水凝胶通过兔子模型中的 M2 巨噬细胞极化促进骨软骨再生。
DOI：
10.1016/j.actbio.2021.04.010
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发表时间：
2021-06-18
影响因子：
9.7
通讯作者：
Yan, Ruijian
中科院分区：
文献类型：
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作者：
Jiang, Guangyao;Li, Sihao;Yan, Ruijian
骨软骨再生是组织工程中炎症免疫、宿主细胞反应和植入物降解的协调过程。在此，在兔模型中研究了使用数字微镜装置（DMD）技术制造的富血小板血浆（PRP）-明胶甲基丙烯酰基（GelMA）水凝胶支架用于骨软骨修复的效果。制备不同PRP浓度的GelMA水凝胶，并研究其对骨髓间充质干细胞（BMSCs）和巨噬细胞体外极化的作用。将20%的PRP掺入到水凝胶中显示出对BMSCs的增殖、迁移、成骨和软骨分化的最佳效果。20% PRP-GelMA（v/v）水凝胶也促进了M2极化，Arg 1和CD 206表达较高。与20%PRP组相比，50%PRP组在BMSCs中表现出相似的生物学作用，但成骨程度较低。在体内研究中，20% PRP-GelMA复合材料用于骨软骨重建，并显示出比使用纯GelMA水凝胶观察到的更多的软骨和软骨下骨再生。与未处理组相比，PRP-GelMA组在三个时间点表现出更多的M2巨噬细胞浸润和更少的M1巨噬细胞呈递。PRP-GelMA组Arg 1的表达在6周时显著增加，但在12周时降至较低水平，而CD 163显示持续高表达直至18周。我们的研究结果表明，3D打印的PRP-GelMA复合材料可以通过M2极化的免疫调节促进骨软骨修复，并可能成为骨软骨组织工程的潜在候选者。显著性声明PRP-GelMA水凝胶促进BMSCs的迁移以及成骨和软骨分化。PRP-GelMA水凝胶参与了巨噬细胞的免疫调节和M1向M2的转化。PRPGelMA水凝胶协调并促进了几种重叠的骨软骨修复事件，包括动态免疫调节、MSC的趋化性和骨软骨分化。PRP-GelMA水凝胶显示出上级的软骨和软骨下骨修复特性。(c)2021 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Osteochondral regeneration is an orchestrated process of inflammatory immunity, host cell response, and implant degradation in tissue engineering. Here, the effects of a platelet-rich plasma (PRP)-gelatin methacryloyl (GelMA) hydrogel scaffold fabricated using the digital micro-mirror device (DMD) technique for osteochondral repair were investigated in a rabbit model. GelMA hydrogels with different PRP concentrations were fabricated, and their roles in bone marrow mesenchymal stem cells (BMSCs) and macrophage polarization in vitro were investigated. The incorporation of 20% PRP into the hydrogel showed optimal effects on the proliferation, migration, and osteogenic and chondrogenic differentiation of BMSCs. The 20% PRP-GelMA (v/v) hydrogel also promoted M2 polarization with high expression of Arg1 and CD206. Compared to the 20% PRP group, the 50% PRP group showed similar biological roles in BMSCs but less extent of osteogenesis. In the vivo study, the 20% PRP-GelMA composite was used for osteochondral reconstruction and showed more cartilage and subchondral bone regeneration than that observed using the pure GelMA hydrogel. The PRP-GelMA group exhibited more M2 macrophage infiltration and less M1 macrophage presentation at three time points as compared to the nontreatment group. The expression of Arg1 in the PRP-GelMA group increased significantly at 6 weeks but decreased to a lower level at 12 weeks, while CD163 showed sustained high expression until 18 weeks. Our findings demonstrated that the 3D-printed PRP-GelMA composite could promote osteochondral repair through immune regulation by M2 polarization and could be a potential candidate for osteochondral tissue engineering. Statement of significance PRP-GelMA hydrogels promoted the migration and osteogenic and chondrogenic differentiation of BMSCs. PRP-GelMA hydrogels participated in immune regulation and M1-to-M2 transition of macrophages. PRPGelMA hydrogels coordinated and promoted several overlapping osteochondral repair events, including dynamic immune regulation, chemotaxis of MSCs, and osteochondral differentiation. PRP-GelMA hydro gels showed superior cartilage and subchondral bone repair properties. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.