Department of Oral Implantology, School of Stomatology, Jilin University, Changchun 130021, China.
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, China.
Molecules. 2019 Apr 28;24(9):1669. doi: 10.3390/molecules24091669.
Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide's biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.
成骨肽已被报道在体外有效指导间充质干细胞成骨分化和体内骨形成。因此，开发新型生物材料用于控制支架中成骨肽的递送而不降低肽的生物活性是非常需要的。为了有效实现个性化骨再生修复大的骨缺损，通过原始的低温 3D 打印方法，制备了一种新型的生物活性聚（乳酸-共-乙醇酸）（PLGA）/β-磷酸三钙（β-TCP）复合支架，其中原位负载了氧化石墨烯（GO）和骨形态发生蛋白（BMP）-2 样肽（PTG/P）。支架的机械性能可与人体松质骨相媲美，且具有分级多孔结构。GO 的加入进一步提高了支架的润湿性和机械强度。原位负载的肽保留了高水平的生物活性，并且 GO 的负载进一步调节了肽的释放，使其更加持续。我们的体外研究表明，PTG/P 支架促进了大鼠骨髓间充质干细胞向支架内的生长，并增强了成骨分化。此外，体内研究表明，具有持续肽释放的新型 PTG/P 支架能够显著促进骨缺损中的骨再生。因此，具有定制形状、改善的机械强度、持续肽释放和优异成骨能力的新型生物活性 PTG/P 支架在骨组织再生中有很大的潜力。
