Samorezov Julia E, Headley Emma B, Everett Christopher R, Alsberg Eben
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.
Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.
J Biomed Mater Res A. 2016 Jun;104(6):1387-97. doi: 10.1002/jbm.a.35668. Epub 2016 Feb 18.
Human adipose-derived stem cells (hASCs) show great potential for healing bone defects. Bone morphogenetic protein-2 (BMP-2) has been reported to stimulate their osteogenic differentiation both in vitro and in vivo. Here, methacrylated gelatin (GelMA) hydrogels were evaluated as a system to deliver BMP-2 to encapsulated hASCs from two different donors, and BMP-2 delivered from the hydrogels was compared to BMP-2 presented exogenously in culture media. GelMA hydrogels were shown to provide sustained, localized presentation of BMP-2 due to electrostatic interactions between the growth factor and biomaterial after an initial burst release. Both donors exhibited similar responses to the loaded and exogenous growth factor; BMP-2 from the hydrogels had a statistically significant effect on hASC osteogenic differentiation compared to exogenous BMP-2. Expression of alkaline phosphatase was accelerated, and cells in hydrogels with loaded BMP-2 deposited more calcium at one, two, and four weeks than cells without BMP-2 or with the growth factor presented in the media. There were no statistically significant differences in calcium content between groups with 25, 50, or 100 µg/mL loaded BMP-2, suggesting that using a lower growth factor dose may be as effective as a higher loading amount in this system. Taken together, these findings suggest that controlled delivery of BMP-2 from the GelMA enhances its osteogenic bioactivity compared to free growth factor presented in the media. Thus, the GelMA system is a promising biomaterial for BMP-2-mediated hASC osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1387-1397, 2016.
人脂肪来源干细胞(hASC)在治疗骨缺损方面显示出巨大潜力。据报道,骨形态发生蛋白2(BMP-2)在体外和体内均能刺激其成骨分化。在此,甲基丙烯酸化明胶(GelMA)水凝胶被评估为一种将BMP-2递送至封装的来自两个不同供体的hASC的系统,并将水凝胶递送的BMP-2与培养基中外源呈现的BMP-2进行比较。结果表明,GelMA水凝胶在初始爆发释放后,由于生长因子与生物材料之间的静电相互作用,能够持续、局部地呈现BMP-2。两个供体对负载的和外源生长因子均表现出相似的反应;与外源BMP-2相比,水凝胶中的BMP-2对hASC成骨分化具有统计学上的显著影响。碱性磷酸酶的表达加快,与未添加BMP-2或培养基中添加生长因子的细胞相比,负载BMP-2的水凝胶中的细胞在1周、2周和4周时沉积了更多的钙。负载25、50或100μg/mL BMP-2的组之间钙含量无统计学显著差异,这表明在该系统中使用较低的生长因子剂量可能与较高的负载量一样有效。综上所述,这些发现表明,与培养基中游离生长因子相比,从GelMA中可控递送BMP-2可增强其成骨生物活性。因此,GelMA系统是一种用于BMP-2介导的hASC成骨的有前景的生物材料。©2016威利期刊公司。《生物医学材料研究杂志》A部分:第104A卷:1387 - 1397页,2016年。