Yu Li, Cai Yan, Wang Huan, Pan Liangbin, Li Jiaying, Chen Song, Liu Zhao, Han Fengxuan, Li Bin
College of Chemistry, Chemical Engineering and Materials Science, Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Acta Biomater. 2020 Aug;112:75-86. doi: 10.1016/j.actbio.2020.05.041. Epub 2020 Jun 4.
Bone injuries are common and new strategies are desired for achieving ideal bone regeneration for bone defect repair. Scaffolds with bone-mimicking characteristics may provide an appropriate microenvironment to promote bone regeneration. Meanwhile, mechanical stimulation effectively regulates a wide range of cellular behaviors such as cell proliferation and differentiation. In this study, biomimetic multi-layer cell-collagen constructs with angle-ply structural feature were prepared by assembling micropatterned collagen membranes on which aligned MC3T3-E1 cells were cultured. The anisotropic microgrooved collagen membranes effectively guided the alignment of cells and promoted the osteogenic differentiation of them. To further promote cell differentiation and extracellular matrix production, the multi-layer cell-collagen constructs were cultured under mechanical conditioning through cyclic stretching. It was found that the constructs with both cell alignment and mechanical conditioning resulted in better osteogenic potential than those with cell alignment or mechanical conditioning alone. Upon implantation into the critical-sized calvarial defects of mice, the constructs with both cell alignment and mechanical conditioning achieved best new bone formation efficacy. Together, findings from this study reveal that synergized use of microstructural and mechanical cues may provide an effective new approach toward bone regeneration. STATEMENT OF SIGNIFICANCE: Biomimicking is an effective strategy to promote bone regeneration for repairing bone defects. Although numerous studies which micro-structurally mimicked native bone using various scaffolds, far less studies have paid attention to the mechanical environment of bone. In this study, angle-ply collagen membrane-supported cell sheets were prepared and pre-conditioned using mechanical loading prior to implantation at bone defects. The constructs with cell alignment and subjected to mechanical conditioning resulted in better osteogenic differentiation of cells in vitro and new bone formation in vivo than those with cell alignment or mechanical conditioning alone. Therefore, recapitulation of both microstructural and mechanical features of native bone may result in a synergistic effect and provides an effective approach toward bone regeneration.
骨损伤很常见，人们期望有新的策略来实现理想的骨再生以修复骨缺损。具有仿骨特性的支架可为促进骨再生提供合适的微环境。同时，机械刺激能有效调节多种细胞行为，如细胞增殖和分化。在本研究中，通过组装微图案化胶原膜（其上培养有排列整齐的MC3T3-E1细胞）制备了具有角铺层结构特征的仿生多层细胞-胶原构建体。各向异性的微槽胶原膜有效地引导了细胞的排列并促进了它们的成骨分化。为进一步促进细胞分化和细胞外基质生成，通过循环拉伸对多层细胞-胶原构建体进行机械条件培养。结果发现，兼具细胞排列和机械条件培养的构建体比单独具有细胞排列或机械条件培养的构建体具有更好的成骨潜力。将这些构建体植入小鼠的临界尺寸颅骨缺损处后，兼具细胞排列和机械条件培养的构建体实现了最佳的新骨形成效果。总之，本研究结果表明，微观结构和机械信号的协同使用可能为骨再生提供一种有效的新方法。意义声明：仿生是促进骨再生以修复骨缺损的有效策略。尽管有许多研究使用各种支架在微观结构上模仿天然骨，但关注骨的力学环境的研究要少得多。在本研究中，制备了角铺层胶原膜支撑的细胞片，并在植入骨缺损之前使用机械加载进行预处理。兼具细胞排列并经过机械条件培养的构建体在体外比单独具有细胞排列或机械条件培养的构建体具有更好的细胞成骨分化能力，在体内也能形成更多新骨。因此，重现天然骨的微观结构和力学特征可能会产生协同效应，并为骨再生提供一种有效的方法。
