3D GelMA ICC Scaffolds Combined with SW033291 for Bone Regeneration by Modulating Macrophage Polarization.
3D GelMA ICC Scaffolds Combined with SW033291 for Bone Regeneration by Modulating Macrophage Polarization.
复制标题
3D GelMA ICC 支架与 SW033291 相结合，通过调节巨噬细胞极化实现骨再生
DOI：
10.3390/pharmaceutics13111934
复制
发表时间：
2021-11-16
期刊：
影响因子：
5.4
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Jiang Q;Bai G;Liu X;Chen Y;Xu G;Yang C;Zhang Z
尽管已发现骨髓间充质干细胞(BMSCs)和巨噬细胞之间的相互作用在修复骨缺损中起着关键作用，但开发一种能够同时调节成骨分化和巨噬细胞极化的理想组织工程支架仍然是一个挑战。因此，本研究提出了一种基于三维明胶甲基丙烯酰基倒置胶体晶体(3D GelMA ICC)支架和活性15-羟基前列腺素脱氢酶(15-PGDH)抑制剂SW033291的骨缺损治疗新策略。首次采用胶体模板法制备了三维GelMA ICC支架，该支架具有良好的细胞黏附性，并且由于其均匀的孔道连通性，促进了巨噬细胞与BMSCs之间的细胞间相互作用。联合应用SW033291后，骨髓间充质干细胞在GelMA ICC支架上的前列腺素E2(PGE2)释放明显上调，巨噬细胞M2极化明显增强。反过来，通过对M2巨噬细胞的旁分泌调节，进一步促进BMSCs的增殖和成骨分化，最终通过形成GelMA ICC支架周围促再生的局部免疫微环境，最终导致体内更多的新骨形成。我们的研究结果表明，3D GelMA ICC支架与SW033291相结合，有可能成为一种有效的骨再生组织工程策略。
Despite the interaction between bone marrow mesenchymal stem cells (BMSCs) and macrophages has been found to play a critical role in repairing bone defects, it remains a challenge to develop a desirable tissue engineering scaffold for synchronous regulation of osteogenic differentiation and macrophage polarization. Herein, this study proposed a novel strategy to treat bone defects based on three-dimensional Gelatin Methacryloyl Inverted Colloidal Crystal (3D GelMA ICC) scaffold and an active 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor SW033291. Specifically, the 3D GelMA ICC scaffolds were firstly prepared by colloidal templating method, which displayed good cell attachment and promoted intercellular interaction among macrophage and BMSCs due to its uniform pore interconnectivity. By combined use of SW033291, the release of Prostaglandin E2 (PGE2) from BMSCs on the GelMA ICC scaffold was significantly upregulated and macrophages M2 polarization was markedly increased. In turn, BMSCs proliferation and osteogenic differentiation was further enhanced by paracrine regulation of M2 macrophage, and thus finally caused more in vivo new bone formation by shaping up a pro-regenerative local immune microenvironment surrounding GelMA ICC scaffold. Our findings demonstrate the potential of 3D GelMA ICC scaffolds combined with SW033291 to become an effective tissue engineering strategy for bone regeneration.
登录
查看更多内容
影响因子：
6.2
作者：
Amin, Shreyasee;Achenbach, Sara J.;Atkinson, Elizabeth J.;Khosla, Sundeep;Melton, L. Joseph, III
通讯作者：
Melton, L. Joseph, III
影响因子：
12.7
作者：
Huang R;Wang X;Zhou Y;Xiao Y
通讯作者：
Xiao Y
影响因子：
3.3
作者：
Ding, Dah-Ching;Shyu, Woei-Cherng;Lin, Shinn-Zong
通讯作者：
Lin, Shinn-Zong
影响因子：
9.7
作者：
Seebach, Elisabeth;Freischmidt, Holger;Richter, Wiltrud
通讯作者：
Richter, Wiltrud
影响因子：
14
作者：
Ruecker, Martin;Laschke, Matthias W.;Menger, Michael D.
通讯作者：
Menger, Michael D.