骨整合
骨愈合
细胞生物学
再生(生物学)
巨噬细胞极化
细胞因子
生物医学工程
成骨细胞
材料科学
骨免疫学
化学
植入
巨噬细胞
免疫学
医学
解剖
生物
体外
外科
生物化学
兰克尔
基因
激活剂(遗传学)
作者
Yaping Wang,Zujian Feng,Xiang Liu,Chunfang Yang,Rui Gao,Wenshuai Liu,Wenbin Ouyang,Anjie Dong,Chuangnian Zhang,Pingsheng Huang,Weiwei Wang
摘要
Titanium alloy has been widely used in orthopedic surgeries as bone defect filling. However, the regeneration of high-quality new bones is limited due to the pro-inflammatory microenvironment around implants, resulting in a high occurrence rate of implant loosening or failure in osteological therapy. In this study, extracellular matrix-mimetic polysaccharide hydrogel co-delivering BMP-2 and interleukin (IL)-4 was composited with 3D printed titanium alloy to promote the osseointegration and regulate macrophage response to create a pro-healing microenvironment in bone defect. Notably, it is discovered from the bioinformatics data that IL-4 and BMP-2 could affect each other through multiple signal pathways to achieve a synergistic effect toward osteogenesis. The composite scaffold significantly promoted the osteoblast differentiation and proliferation of human bone marrow mesenchyme stem cells (hBMSCs). The repair of large-scale femur defect in rat indicated that the dual-cytokine-delivered composite scaffold could manipulate a lower inflammatory level in situ by polarizing macrophages to M2 phenotype, resulting in superior efficacy of mature new bone regeneration over the treatment of native titanium alloy or that with an individual cytokine. Collectively, this work highlights the importance of M2-type macrophages-enriched immune-environment in bone healing. The biomimetic hydrogel-metal implant composite is a versatile and advanced scaffold for accelerating in vivo bone regeneration, holding great promise in treating orthopedic diseases.
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