Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
Int J Mol Sci. 2022 Jul 28;23(15):8347. doi: 10.3390/ijms23158347.
Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, swelling of soft tissue in the neck, etc. Therefore, safely and effectively applying growth factors in bone repair biomaterials comes to be an urgent problem that needs to be addressed. In this study, an appropriate concentration (50 ng/mL) of Wnt3a was used to pretreat the 3D-bioprinting gelatin methacryloyl(GelMA)/polycaprolactone(PCL) scaffold loaded with bone marrow stromal cell line ST2 for 24 h. This pretreatment promoted the cell proliferation, osteogenic differentiation, and mineralization of ST2 in the scaffold in vitro, and enhanced angiogenesis and osteogenesis after being implanted in critical-sized mouse calvarial defects. On the contrary, the inhibition of Wnt/β-catenin signaling in ST2 cells reduced the bone repair effect of this scaffold. These results suggested that ST2/GelMA/PCL scaffolds pretreated with an appropriate concentration of Wnt3a in culture medium could effectively enhance the osteogenic and angiogenic activity of bone repair biomaterials both in vitro and in vivo. Moreover, it would avoid the side effects caused by the supraphysiological concentrations of growth factors. This functionalized scaffold with osteogenic and angiogenic activity might be used as an outstanding bone substitute for bone regeneration and repair.
生长因子通常用于提高生物材料的生物活性，以制造用于骨缺损修复的生物功能化骨移植物。然而，为了提高生物活性而使用超生理浓度的生长因子可能会导致严重的副作用，如异位骨形成、神经根炎、颈部软组织肿胀等。因此，安全有效地将生长因子应用于骨修复生物材料成为一个亟待解决的问题。在本研究中，采用适宜浓度（50ng/ml）的 Wnt3a 预处理负载骨髓基质细胞系 ST2 的 3D 生物打印明胶甲基丙烯酰（GelMA）/聚己内酯（PCL）支架 24 小时。这种预处理促进了 ST2 在支架中的细胞增殖、成骨分化和矿化，并且在植入临界大小的小鼠颅骨缺损后增强了血管生成和骨生成。相反，Wnt/β-catenin 信号通路在 ST2 细胞中的抑制作用降低了该支架的骨修复效果。这些结果表明，在培养物中用适宜浓度的 Wnt3a 预处理的 ST2/GelMA/PCL 支架可以有效地增强骨修复生物材料的成骨和成血管活性，无论是在体外还是体内。此外，它可以避免生长因子超生理浓度引起的副作用。这种具有成骨和成血管活性的功能化支架可能可用作骨再生和修复的优秀骨替代物。
