Machado-Paula Mirian M, Corat Marcus A F, de Vasconcellos Luana M R, Araújo Juliani C R, Mi Gujie, Ghannadian Paria, Toniato Tatiane V, Marciano Fernanda R, Webster Thomas J, Lobo Anderson O
Institute of Research and Development, University of Vale do Paraiba, São José dos Campos, SP 12244 - 000, Brazil.
Nanomedicine Laboratory, Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, United States.
ACS Appl Bio Mater. 2022 Mar 21;5(3):1013-1024. doi: 10.1021/acsabm.1c00365. Epub 2022 Feb 16.
Clinically, bone tissue replacements and/or bone repair are challenging. Strategies based on well-defined combinations of osteoconductive materials and osteogenic cells are promising to improve bone regeneration but still require improvement. Herein, we combined polycaprolactone (PCL) fibers, carbon nanotubes (CNT), and hydroxyapatite (nHap) nanoparticles to develop the next generation of bone regeneration material. Fibers formed by rotary jet spinning (RJS) instead of traditional electrospinning (ES) with embedded bone marrow mesenchymal stem cells (BMMSCs) showed the best outcomes to repair rat calvarial defects after 6 weeks. To understand this, it was observed that different morphologies were formed depending on the manufacturing method used. RJS fibers presented a particular topography with rough fibers, which allowed for better cellular growth and cell spreading in vitro around and into a three-dimensional (3D) mesh, while fibers made by ES were more smooth and cellular growth was only measured on the 3D mesh surface. The fibers with incorporated nHap/CNT nanoparticles enhanced in vitro cell performance as indicated by more cellular proliferation, alkaline phosphatase activity, proliferation, and deposition of calcium. Greater bone neoformation occurred by combining three characteristics: the presence of nHap and CNT nanoparticles, the topography of the RJS fibers, and the addition of BMMSCs. RJS fibers with nanoparticles and seeded with BMMSCs showed 10 136 mm of bone neoformation, meaning a 10-fold increase compared to using RJS only and BMMSCs (0.853 mm) and a 5-fold increase from using ES only (2054 mm) after 6 weeks of implantation. Conversely, none of these approaches used individually showed any significant difference for in vivo bone neoformation, suggesting that their combination is essential for optimizing bone formation. In summary, our work generated a potential material composed of well-defined combinations of suitable scaffolds seeded with BMMSCs for enhancing numerous orthopedic tissue engineering applications.
临床上，骨组织替代物和/或骨修复具有挑战性。基于具有良好定义的骨传导材料和成骨细胞组合的策略有望改善骨再生，但仍需改进。在此，我们将聚己内酯（PCL）纤维、碳纳米管（CNT）和羟基磷灰石（nHap）纳米颗粒结合起来，开发下一代骨再生材料。通过旋转喷射纺丝（RJS）而非传统静电纺丝（ES）形成的纤维，与嵌入的骨髓间充质干细胞（BMMSC）相结合，在6周后显示出修复大鼠颅骨缺损的最佳效果。为了解其中原因，研究发现根据所使用的制造方法会形成不同的形态。RJS纤维呈现出具有粗糙纤维的特殊形貌，这使得细胞在体外围绕并进入三维（3D）网格时能够更好地生长和铺展，而ES制成的纤维则更光滑，细胞生长仅在3D网格表面进行测量。掺入nHap/CNT纳米颗粒的纤维增强了体外细胞性能，表现为更多的细胞增殖、碱性磷酸酶活性、增殖以及钙的沉积。通过结合三个特征实现了更大程度的骨新形成：nHap和CNT纳米颗粒的存在、RJS纤维的形貌以及BMMSC的添加。植入6周后，含有纳米颗粒并接种BMMSC的RJS纤维显示出10136毫米的骨新形成，这意味着与仅使用RJS和BMMSC（0.853毫米）相比增加了10倍，与仅使用ES（2054毫米）相比增加了5倍。相反，这些方法单独使用时在体内骨新形成方面均未显示出任何显著差异,这表明它们的组合对于优化骨形成至关重要。总之，我们的工作产生了一种潜在的材料，该材料由接种BMMSC的合适支架的良好定义组合组成，可增强众多骨科组织工程应用。
Zotero 插件