In bone tissue engineering (BTE), most of the currently developed scaffolds still lack the ability to demonstrate high porosity and high mechanical strength simultaneously or the ability to maintain bioactivity and sustained release of loaded biofactors. In this work, we constructed an anisotropic triple-pass tubular framework within a lyophilized porous GEL scaffold using FP, which was prepared by coating DEX-covered Whatman paper (WP) using the silk fibroin (SF) membrane with β-sheet conformation. This novel structural design endowed the functionalized paper frame (FPF)/scaffold implant high porosity, high mechanical strength, and sustained DEX delivery capability. Specifically, its porosity was as high as 88.2%, approximating that of human cancellous bone. The pore diameters of the implant ranged from 50 to 350 μm with an average pore diameter of 127.7 μm, indicating proper pore sizes for successful diffusion of essential nutrients/oxygen and bone tissue-ingrowth. Owing to the construction of double-network-like structure, the FPF/scaffold implant demonstrated excellent mechanical properties both in dry (174.7 MPa in elastic modulus and 14.9 MPa in compressive modulus) and wet states (59.0 MPa in elastic modulus and 3.3 MPa in compressive modulus), indicating its feasibility for in vivo implantation. Besides, the FPF/scaffold implant exhibited long-term DEX releasing behavior (over 50 days) with constant release rate in phosphate buffered saline (PBS). Murine osteoblasts MC3T3-E1 cultured in the porous FPF/scaffold implant had excellent viability. Furthermore, the cells cocultured with the FPF/scaffold implant showed positive proliferation, osteogenic differentiation, and calcium deposition. Twenty-eight days after implantation, extensive osteogenesis was observed in the rats treated with the FPF/scaffold implants. The anisotropic triple-pass tubular framework of the FPF/scaffold implant demonstrates structural similarities to the long bone. Therefore, this novel FPF/scaffold implant could be a better alternative for long bone defect repair.

中文翻译：

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使用负载地塞米松的功能化Whatman纸在冻干的多孔明胶支架中构建各向异性三遍管状结构，以增强其机械强度并促进成骨作用

在骨组织工程学（BTE）中，大多数当前开发的支架仍然缺乏同时显示出高孔隙率和高机械强度的能力，或者缺乏维持生物活性和负载生物因子持续释放的能力。在这项工作中，我们使用FP在冻干的多孔GEL支架内构建了各向异性的三次通过管状骨架，该骨架是通过使用具有β-sheet构象的丝素蛋白（SF）膜涂覆DEX覆盖的Whatman纸（WP）制备的。这种新颖的结构设计赋予了功能化纸架（FPF）/支架植入物高孔隙率，高机械强度和持续的DEX传递能力。具体而言，其孔隙率高达88.2％，接近人类松质骨的孔隙率。植入物的孔径范围为50至350μm，平均孔径为127.7μm，表明适当的孔径可成功地扩散必需的营养素/氧气和骨骼组织向内生长。由于采用了双网状结构，FPF /支架植入物在干态（弹性模量为174.7 MPa，压缩模量为14.9 MPa）和湿态（弹性模量为59.0 MPa，在弹性模量为3.3 MPa）下均表现出优异的机械性能。压缩模量），表明其可行性体内植入。此外，FPF /支架植入物在磷酸盐缓冲盐水（PBS）中表现出长期的DEX释放行为（超过50天），并且释放速率恒定。在多孔FPF /支架植入物中培养的鼠成骨细胞MC3T3-E1具有出色的生存能力。此外，与FPF /支架植入物共培养的细胞显示出正增殖，成骨分化和钙沉积。植入后28天，在用FPF /支架植入物治疗的大鼠中观察到广泛的成骨作用。FPF /支架植入物的各向异性三遍管状框架显示出与长骨的结构相似性。因此，这种新颖的FPF /支架植入物可能是长骨缺损修复的更好选择。