Bettahalli N M S, Groen N, Steg H, Unadkat H, de Boer J, van Blitterswijk C A, Wessling M, Stamatialis D
Membrane Technology Group, Faculty of Science and Technology, PO Box 217, 7500 AE, Enschede, The Netherlands.
J Tissue Eng Regen Med. 2014 Feb;8(2):106-19. doi: 10.1002/term.1504. Epub 2012 Apr 12.
The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of the disease, injury or impairment. Despite the great progress in the field, development of clinically relevantly sized tissues with complex architecture remains a great challenge. This is mostly due to limitations of nutrient and oxygen delivery to the cells and limited availability of scaffolds that can mimic the complex tissue architecture. This study presents the development of a multilayer tissue construct by rolling pre-seeded electrospun sheets [(prepared from poly (l-lactic acid) (PLLA) seeded with C2C12 pre-myoblast cells)] around a porous multibore hollow fibre (HF) membrane and its testing using a bioreactor. Important elements of this study are: 1) the medium permeating through the porous walls of multibore HF acts as an additional source of nutrients and oxygen to the cells, which exerts low shear stress (controllable by trans membrane pressure); 2) application of dynamic perfusion through the HF lumen and around the 3D construct to achieve high cell proliferation and homogenous cell distribution across the layers, and 3) cell migration occurs within the multilayer construct (shown using pre-labeled C2C12 cells), illustrating the potential of using this concept for developing thick and more complex tissues.
组织工程这一快速发展的领域生产出能够恢复、维持或改善组织或器官功能的活体替代物。与标准疗法不同，这些工程化产品能够与患者自身组织整合，为疾病、损伤或机能障碍提供潜在的永久性和特异性治疗。尽管该领域取得了巨大进展，但开发具有复杂结构且尺寸与临床相关的组织仍然是一项巨大挑战。这主要是由于细胞营养和氧气供应受限，以及能够模拟复杂组织结构的支架材料有限。本研究展示了一种多层组织构建体的开发过程，该构建体是通过将预先接种了C2C12成肌前体细胞的电纺丝片材（由聚左旋乳酸（PLLA）制备）围绕多孔多腔中空纤维（HF）膜卷绕而成，并使用生物反应器对其进行测试。本研究的重要要点包括：1）透过多孔多腔HF壁渗透的培养基可作为细胞额外的营养和氧气来源，且施加的剪切应力较低（可通过跨膜压力控制）；2）通过HF管腔和3D构建体周围进行动态灌注，以实现细胞的高增殖和各层间细胞的均匀分布；3）细胞在多层构建体内发生迁移（使用预先标记的C2C12细胞进行展示），这表明利用这一概念开发更厚且更复杂组织的潜力。
