Androulidakis Charalampos, Svitina Hanna, Ioannidis Konstantinos, Dunn Alexander R, Papantoniou Ioannis
Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat 49, PB 813, 3000, Leuven, Belgium; Skeletal Biology and Engineering Research, KU Leuven, ON1 Herestraat 49, PB 813, 3000, Leuven, Belgium; Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.
Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat 49, PB 813, 3000, Leuven, Belgium; Skeletal Biology and Engineering Research, KU Leuven, ON1 Herestraat 49, PB 813, 3000, Leuven, Belgium.
Biomaterials. 2025 Jun;317:123074. doi: 10.1016/j.biomaterials.2024.123074. Epub 2025 Jan 6.
Self-assembled cartilaginous microtissues provide a promising means of repairing challenging skeletal defects and connective tissues. However, despite their considerable promise in tissue engineering, the mechanical response of these engineered microtissues is not well understood. Here we examine the mechanical and viscoelastic response of progenitor cell aggregates formed from human primary periosteal cells and the resulting cartilaginous microtissues under large deformations as might be encountered in vivo. We find that the mechanical response of these tissues is strongly size dependent due to surface tension effects, with a scaling law for the Young's modulus of E ∝ D, where D is the diameter of the tissues, and m varies with the tissue type. Similar size effects are found to govern the interfacial surface tension and the viscosity. In addition, these microtissues are extremely resilient, as they sustain over 90 % of compressive strain without mechanical failure. Stress relaxation experiments reveal a fast stress dissipation at short time scale within a few seconds, followed by oscillations in measured stresses that depend on actomyosin contractility. In summary, these experiments reveal the remarkable and unanticipated resilience of cartilaginous microtissues under large mechanical strains, a property that may facilitate their use in a variety of tissue engineering applications. More broadly, our data highlight the importance of surface tensions in determining the mechanical properties of tissues on the micron and the mm length scales.
自组装软骨微组织为修复具有挑战性的骨骼缺损和结缔组织提供了一种很有前景的方法。然而，尽管它们在组织工程中有很大的前景，但这些工程化微组织的力学响应尚未得到很好的理解。在这里，我们研究了由人原代骨膜细胞形成的祖细胞聚集体以及由此产生的软骨微组织在体内可能遇到的大变形下的力学和粘弹性响应。我们发现，由于表面张力效应，这些组织的力学响应强烈依赖于尺寸，杨氏模量的标度律为E ∝ D，其中D是组织的直径，m随组织类型而变化。类似的尺寸效应也被发现控制着界面表面张力和粘度。此外，这些微组织具有极强的弹性，因为它们能承受超过90%的压缩应变而不发生机械失效。应力松弛实验表明，在几秒钟的短时间尺度内应力快速消散，随后测量到的应力出现振荡，这取决于肌动球蛋白的收缩性。总之，这些实验揭示了软骨微组织在大机械应变下具有显著且出人意料的弹性，这一特性可能有助于它们在各种组织工程应用中的使用。更广泛地说，我们的数据突出了表面张力在确定微米和毫米长度尺度上组织力学性能方面的重要性。
