Purpose: Musculoskeletal soft tissues possess highly aligned extracellular collagenous networks that provide structure and strength. Such an organization dictates tissue-specific mechanical properties but can be difficult to replicate by engineered biological substitutes. Nanofibrous electrospun scaffolds have demonstrated the ability to control cell-secreted collagen alignment, but concerns exist regarding their scalability for larger and anatomically relevant applications. Additive manufacturing processes, such as melt extrusion-based 3D-Bioplotting, allow fabrication of structurally relevant scaffolds featuring highly controllable porous microarchitectures.Materials and Methods: In this study, we investigate the effects of 3D-bioplotted scaffold design on the compressive elastic modulus of neotissue formed in vivo in a subcutaneous rat model and its correlation with the alignment of ECM collagen fibers. Polycaprolactone scaffolds featuring either 100 or 400 µm interstrand spacing were implanted for 4 or 12 weeks, harvested, cryosectioned, and characterized using atomic-force-microscopy-based force mapping.Results: The compressive elastic modulus of the neotissue formed within the 100 µm design was significantly higher at 4 weeks (p < 0.05), but no differences were observed at 12 weeks. In general, the tissue stiffness was within the same order of magnitude and range of values measured in native musculoskeletal soft tissues including the porcine meniscus and anterior cruciate ligament. Finally, a significant positive correlation was noted between tissue stiffness and the degree of ECM collagen fiber alignment (p < 0.05) resulting from contact guidance provided by scaffold strands.Conclusion: These findings demonstrate the significant effects of 3D-bioplotted scaffold microarchitectures in the organization and sub-tissue-level mechanical properties of ECM in vivo.

中文翻译：

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体内形成的组织的机械特性受 3D 生物绘图支架微结构的影响，并与 ECM 胶原纤维排列相关。

目的：肌肉骨骼软组织具有高度对齐的细胞外胶原网络，可提供结构和强度。这种组织决定了组织特定的机械性能，但工程生物替代品可能难以复制。纳米纤维静电纺丝支架已证明能够控制细胞分泌的胶原排列，但对其在更大和解剖学相关应用中的可扩展性存在担忧。增材制造工艺，例如基于熔体挤出的 3D-Bioplotting，允许制造具有高度可控多孔微结构的结构相关支架。材料和方法：在这项研究中，我们研究了 3D 生物绘图支架设计对皮下大鼠模型中体内形成的新组织的压缩弹性模量的影响及其与 ECM 胶原纤维排列的相关性。将具有 100 或 400 µm 股间间距的聚己内酯支架植入 4 或 12 周，收获、冷冻切片，并使用基于原子力显微镜的力图进行表征。结果：在 100 µm 设计中形成的新组织的压缩弹性模量4 周时显着升高（p < 0.05），但在 12 周时未观察到差异。一般而言，组织刚度与在天然肌肉骨骼软组织（包括猪半月板和前交叉韧带）中测量的值的数量级和范围相同。最后，