<br>活跃的成骨细胞还是静止的骨衬细胞？前成骨细胞的命运由体外 2.5D 仿生培养系统的曲率和硬度精心安排,Advanced Healthcare Materials

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活跃的成骨细胞还是静止的骨衬细胞？前成骨细胞的命运由体外 2.5D 仿生培养系统的曲率和硬度精心安排
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-11-06 , DOI: 10.1002/adhm.202302222
Hélène Ozanne ₁ , Loïc Moubri ₁ , Léa Abou-Nassif ₁ , Olivier Thoumire ₁ , Aline Echalard ₁ , Sandrine Morin-Grognet ₁ , Hassan Atmani ₁ , Guy Ladam ₁ , Béatrice Labat ₁

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仿生细胞培养系统需要为骨细胞提供更多生理相关的微环境。这里，提出了一个简单的 2.5D 培养平台，通过使用砂纸砂粒作为主模具和两种聚二甲基硅氧烷 (PDMS) 的刚度配方，将可调节的刚度和模拟骨形貌的表面特征结合起来。随后的复制品完美地符合磨粒并再现相应的负浮雕，其中空腔由凸边缘分隔开。仿生学还通过使用逐层 (LbL) 方法的细胞外基质 (ECM) 类薄膜涂层来提供。地形特征、交替的凹凸结构驱动前成骨细胞的组织和形态。引人注目的是，曲率协调了前成骨细胞的参与，i）成熟为活性成骨细胞，能够产生致密的胶原基质，最终在空腔中矿化，ii）边缘容纳静止细胞，合成非常薄的未成熟胶原层，没有矿化。总之，目前的体外培养系统模型提供了一个控制前成骨细胞命运的细胞指导性2.5D微环境，导致两个共存的亚群：成熟的成骨细胞和骨衬细胞（BLC）。这种有前景的培养系统为先进的组织工程建模开辟了新途径，并可应用于预细胞化骨生物材料。

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Active Osteoblasts or Quiescent Bone Lining Cells? Preosteoblasts Fate Orchestrated by Curvature and Stiffness of an In Vitro 2.5D Biomimetic Culture System

Biomimetic cell culture systems are required to provide more physiologically relevant microenvironments for bone cells. Here, a simple 2.5D culture platform is proposed, combining adjustable stiffness and surface features that mimic bone topography by using sandpaper grits as master molds with two stiffness formulations of polydimethylsiloxane (PDMS). The subsequent replicas perfectly conform the grits and reproduce the corresponding negative relief with cavities separated by convex edges. Biomimicry is also provided by an extracellular matrix (ECM)-like thin film coating, using the layer-by-layer (LbL) method. The topographical features, alternating concave, and convex structures drive preosteoblasts organization and morphology. Strikingly, curvature orchestrates the commitment of preosteoblasts, with i) maturation to active osteoblasts able to produce a dense collagenous matrix that ultimately mineralizes in the cavities, and ii) edges hosting quiescent cells that synthetize a very thin immature collagen layer with no mineralization. In summary, the present in vitro culture system model offers a cell-instructive 2.5D microenvironment that controls preosteoblasts fate, leading to two coexisting subpopulations: mature osteoblasts and bone lining cells (BLC). This promising culture system opens new avenues to advanced tissue-engineered modeling and can be applied to precellularized bone biomaterials.

更新日期：2023-11-06

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