Jiang Qian, Bai Guo, Liu Xin, Chen Yuxiao, Xu Guangzhou, Yang Chi, Zhang Zhiyuan
Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 639, Zhizaoju Rd, Shanghai 200011, China.
Department of Dental Materials, Shanghai Biomaterials Research & Testing Center, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 427, Jumen Rd, Shanghai 200011, China.
Pharmaceutics. 2021 Nov 16;13(11):1934. doi: 10.3390/pharmaceutics13111934.
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.
尽管已发现骨髓间充质干细胞（BMSCs）与巨噬细胞之间的相互作用在修复骨缺损中起关键作用，但开发一种理想的组织工程支架以同步调节成骨分化和巨噬细胞极化仍然是一项挑战。在此，本研究提出了一种基于三维甲基丙烯酰化明胶反相胶体晶体（3D GelMA ICC）支架和活性15-羟基前列腺素脱氢酶（15-PGDH）抑制剂SW033291治疗骨缺损的新策略。具体而言，首先通过胶体模板法制备3D GelMA ICC支架，由于其均匀的孔隙互连性，该支架表现出良好的细胞附着性，并促进巨噬细胞与BMSCs之间的细胞间相互作用。通过联合使用SW033291，GelMA ICC支架上BMSCs中前列腺素E2（PGE2）的释放显著上调，巨噬细胞M2极化明显增加。反过来，M2巨噬细胞的旁分泌调节进一步增强了BMSCs的增殖和成骨分化，从而最终通过在GelMA ICC支架周围形成促再生局部免疫微环境，导致更多的体内新骨形成。我们的研究结果证明了3D GelMA ICC支架与SW033291结合成为一种有效的骨再生组织工程策略的潜力。
