Univ. Lyon, VetAgro Sup, UPSP ICE 2021, A104, 1 Av. Bourgelat, 69280 Marcy l'Etoile, France.
Univ. Lyon, VetAgro Sup, UPSP ICE 2021, A104, 1 Av. Bourgelat, 69280 Marcy l'Etoile, France; Univ. Lyon, École Centrale de Lyon, 36 Av. Guy de Collongue, 69134 Ecully, France.
Biomater Adv. 2023 Jun;149:213401. doi: 10.1016/j.bioadv.2023.213401. Epub 2023 Mar 25.
Tissue engineering (TE) is the study and development of biological substitutes to restore, maintain or improve tissue function. Tissue engineered constructs (TECs) still present differences in mechanical and biological properties compared to native tissue. Mechanotransduction is the process through which mechanical stimulation triggers proliferation, apoptosis, and extracellular matrix synthesis, among other cell activities. Regarding that aspect, the effect of in vitro stimulations such as compression, stretching, bending or fluid shear stress loading modalities have been extensively studied. A fluid flow used to produce contactless mechanical stimulation induced by an air pulse could be easily achieved in vivo without altering the tissue integrity.
A new air-pulse device for contactless and controlled mechanical simulation of a TECs was developed and validated in this study conducted in the following three phases: 1) conception of the controlled air-pulse device combined with a 3D printed bioreactor; 2) experimental and numerical mechanical characterization of the air-pulse impact by digital image correlation; and 3) achieving sterility and noncytotoxicity of the air-pulse and of the 3D printed bioreactor using a novel dedicated sterilization process.
We demonstrated that the treated PLA (polylactic acid) was noncytotoxic and did not influence cell proliferation. An ethanol/autoclaved sterilization protocol for 3D printed objects in PLA has been developed in this study, enabling the use of 3D printing in cell culture. A numerical twin of the device was developed and experimentally characterized by digital image correlation. It showed a coefficient of determination R = 0.98 between the numerical and averaged experimental surface displacement profiles of the TEC substitute.
The results of the study assessed the noncytotoxicity of PLA for prototyping by 3D printing the homemade bioreactor. A novel sterilization process for PLA was developed in this study based on a thermochemical process. A numerical twin using fluid-structure interaction method has been developed to investigate the micromechanical effects of air pulses inside the TEC, which cannot all be measured experimentally, for instance, wave propagation generated during the air-pulse impact. The device could be used to study the cell response to contactless cyclic mechanical stimulation, particularly in TEC with fibroblasts, stromal cells and mesenchymal stem cells, which have been shown to be sensitive to the frequency and strain level at the air-liquid interface.
组织工程（TE）是研究和开发生物替代品，以恢复、维持或改善组织功能。与天然组织相比，组织工程构建物（TEC）在机械和生物学特性方面仍然存在差异。机械转导是指机械刺激触发增殖、凋亡和细胞外基质合成等细胞活动的过程。关于这一方面，已经广泛研究了体外刺激（如压缩、拉伸、弯曲或流体切应力加载方式）的效果。在体内，可以很容易地实现用于产生无接触机械刺激的空气脉冲流，而不会改变组织的完整性。
本研究中开发并验证了一种新的空气脉冲装置，用于 TEC 的无接触和受控机械模拟，该研究分为三个阶段：1）结合 3D 打印生物反应器设计受控空气脉冲装置；2）通过数字图像相关对空气脉冲冲击进行实验和数值机械特性分析；3）使用新型专用灭菌工艺实现空气脉冲和 3D 打印生物反应器的无菌性和非细胞毒性。
我们证明了处理后的 PLA（聚乳酸）无细胞毒性，并且不会影响细胞增殖。本研究开发了一种用于 PLA 3D 打印物体的乙醇/高压灭菌消毒协议，从而使 3D 打印能够用于细胞培养。使用流体结构相互作用方法开发了装置的数值双胞胎，并通过数字图像相关进行了实验特性分析。结果表明，数值和平均实验表面位移轮廓之间的决定系数 R=0.98。
该研究评估了 PLA 通过 3D 打印自制生物反应器进行原型制作的非细胞毒性。本研究基于热化学过程开发了一种新的 PLA 灭菌工艺。使用流体结构相互作用方法开发了数值双胞胎，以研究空气脉冲在 TEC 内部产生的微观机械效应，这些效应无法全部通过实验测量，例如，在空气脉冲冲击过程中产生的波传播。该装置可用于研究细胞对无接触循环机械刺激的反应，特别是在成纤维细胞、基质细胞和间充质干细胞等对空气-液界面处的频率和应变水平敏感的 TEC 中。
