Enhanced bone tissue regeneration using a 3D printed microstructure incorporated with a hybrid nano hydrogel.
Enhanced bone tissue regeneration using a 3D printed microstructure incorporated with a hybrid nano hydrogel.
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DOI：
10.1039/c6nr09652b
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发表时间：
2017-04-20
期刊：
影响因子：
6.7
通讯作者：
Zhang LG
中科院分区：
文献类型：
--
作者：
Heo DN;Castro NJ;Lee SJ;Noh H;Zhu W;Zhang LG
具有仿生机械和化学特性的三维（3D）功能结构是各种再生医学应用的理想选择。在3D制造结构中，这些特性是材料和制造方法的固有特性。在这方面，由于缺乏合适的机械性能以及成功的高仿生要求，目前使用水凝胶进行肌肉骨骼组织修复并不完美。为了克服这一限制，我们开发了一种新型的功能化水凝胶，其具有生物活性金纳米颗粒（GNP），并通过熔融沉积成型（FDM）增强3D打印的微结构，用于骨组织再生。我们使用可生物降解的热塑性聚乳酸（PLA）作为3D打印的微结构，结合光固化明胶水凝胶作为包封基质，用于掺入环状RGD缀合的GNP（RGNP），并研究其机械性能。此外，人脂肪来源的干细胞（ADSC）封装在明胶水凝胶内，并在体外检查活力，形态和成骨分化。结果表明，具有增强3D打印微结构的复合水凝胶的刚度可以容易地调节以模拟人类下颌骨髁突的刚度。包封在复合结构中的ADSC在水凝胶中保持活力，并在3D打印的PLA微结构上表现出优异的铺展性。更重要的是，成骨分化与纳入RGNP促进显着更高的基因表达的成骨特异性因子。因此，增强复合水凝胶适用于干细胞分化控制和骨组织再生。
Three-dimensional (3D) functional constructs with biomimetic mechanical and chemical properties are ideal for various regenerative medicine applications. Within a 3D fabricated construct these properties are intrinsic characteristics of the materials and fabrication method. In this respect, the current use of hydrogels for musculoskeletal tissue repair are not perfect due to the lack of suitable mechanical properties, as well as the high biomimetic requirement for success. To overcome this limitation, we developed a novel functionalized hydrogel with bioactive gold nanoparticles (GNPs) and reinforcing 3D printed microstructure via fused deposition modeling (FDM) for bone tissue regeneration. We used the biodegradable thermoplastic polylactic acid (PLA) as the 3D printed microstructure in combination with photo-curable gelatin hydrogels as the encapsulation matrix for the incorporation of cyclicRGD conjugated GNPs (RGNP), and investigated their mechanical properties. In addition, human adipose-derived stem cells (ADSCs) were encapsulated within the gelatin hydrogel and examined for viability, morphology, and osteogenic differentiation in vitro. The results showed that the stiffness of the composite hydrogel with reinforcing 3D printed microstructure can be readily modulated to simulate the stiffness of the human mandibular condyle. ADSCs encapsulated in the composite structures remained viable within the hydrogel and showed excellent spreading on the 3D printed PLA microstructure. More importantly, osteogenic differentiation with incorporated RGNP promoted significantly higher gene expression of osteogenic specific factors. Therefore, reinforced composite hydrogels are suitable for stem cell differentiation control and bone tissue regeneration.