Biomimetic bone regeneration using angle-ply collagen membrane-supported cell sheets subjected to mechanical conditioning.
Biomimetic bone regeneration using angle-ply collagen membrane-supported cell sheets subjected to mechanical conditioning.
复制标题
DOI：
10.1016/j.actbio.2020.05.041
复制
发表时间：
2020-06
影响因子：
9.7
通讯作者：
Li Yu;Yan Cai;Huan Wang;Liangbin Pan;Jiaying Li;Song Chen;Zhao-hui Liu;F. Han;Bin Li
中科院分区：
文献类型：
--
作者：
Li Yu;Yan Cai;Huan Wang;Liangbin Pan;Jiaying Li;Song Chen;Zhao-hui Liu;F. Han;Bin Li
骨损伤是常见的，骨缺损修复需要新的策略来实现理想的骨再生。具有骨模拟特性的支架可以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细胞增殖、分化等多种细胞行为。本研究通过组装微图胶原膜制备了具有角层结构特征的仿生多层细胞-胶原结构，并在其上培养排列的MC3T3-E1细胞。各向异性微沟胶原膜有效引导细胞排列，促进细胞成骨分化。为了进一步促进细胞分化和细胞外基质的产生，在机械条件下通过循环拉伸培养多层细胞-胶原结构。结果表明，结合细胞排列和机械调节的结构体比仅结合细胞排列和机械调节的结构体具有更好的成骨潜力。植入小鼠临界尺寸颅骨缺损后，同时具有细胞定向和机械调节的构建体的新骨形成效果最好。总之，本研究的发现表明，微观结构和机械线索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修复骨缺损的有效策略。尽管有大量研究利用各种支架在微观结构上模拟天然骨，但对骨的力学环境的关注却很少。在本研究中，制备了角层胶原膜支持的细胞片，并在骨缺损植入前使用机械负荷进行预处理。与细胞排列和机械调节相比，细胞排列和机械调节对体外细胞成骨分化和体内新骨形成有更好的影响。因此，再现原生骨的微观结构和力学特征可能会产生协同效应，并为骨再生提供有效途径。
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 SignificanceBiomimicking 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 cellsin vitroand new bone formationin vivothan 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.