Department of Materials Science and Chemical Engineering, Stony Brook University, NY 11794, USA.
Department of Mechanical Engineering, Technion Israel Institute of Technology, Haifa 3200003, Israel.
Acta Biomater. 2019 Sep 15;96:295-302. doi: 10.1016/j.actbio.2019.07.021. Epub 2019 Jul 15.
Poloxamers, or pluronics, have been proposed as biomimetic substitutes for physiological gels. Concern regarding their ability to resist swelling under fluid flows has impeded their implementation. Using a combination of techniques including cryo-TEM and rapid X-ray imaging, we found that rapid flow rates stabilized the gels against dissolution. Energy balance calculations confirmed that disentanglement of individual micelles was not possible at time scales faster than the reptation time when the system response was that of a solid which dissipated the hydrodynamic force field via cooperative deformation. In-vivo tests were performed where the hydrogel was injected as a substitute for the nucleus pulposus following discectomy in dogs. The results indicated that the gel was still present after 3 months, and radiographs indicated that compression of the disc space was prevented despite the gel being exposed to constant perfusion. STATEMENT OF SIGNIFICANCE: This paper demonstrates a highly unexpected result and counter intuitive result, namely the inverse dependence of the dissociation rate of a physical hydrogel on the flow velocity of the liquid medium. Using cryo-electron microscopy we demonstrate that the gel responds like deformable solid in high flow rates, with minimal dissociation. Since these gels are thermoreversible, they were injected into dogs, where we show that they were a viable alternative to the nucleus pulposus, without dissolution in physiological fluid flows for at least three months.
泊洛沙姆,或聚氧丙烯-聚氧乙烯嵌段共聚物,已被提议作为仿生替代生理凝胶。人们担心它们在流体流动下抵抗溶胀的能力会阻碍它们的应用。我们使用包括低温透射电子显微镜和快速 X 射线成像在内的组合技术发现,快速流速可以稳定凝胶防止溶解。能量平衡计算证实,在比缠结时间更快的时间尺度上,单个胶束的解缠是不可能的,当系统响应为固体时,它通过协同变形耗散流体动力场。在体内测试中,将水凝胶作为椎间盘切除术切除后椎间盘的替代物注入狗体内。结果表明,即使凝胶暴露于持续灌注下,3 个月后仍存在凝胶,并且射线照片表明尽管凝胶受到持续灌注,但椎间盘间隙的压缩得到了防止。意义声明:本文展示了一个非常意外和反直觉的结果,即物理水凝胶的解离速率与液体介质的流速呈反比。使用低温电子显微镜,我们证明在高流速下,凝胶的响应类似于可变形的固体,解离最小。由于这些凝胶是热可逆的,我们将它们注入狗体内,在那里我们表明它们是髓核的可行替代品,在生理流体流动中至少 3 个月不会溶解。