Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong.
Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Colloids Surf B Biointerfaces. 2023 Mar;223:113189. doi: 10.1016/j.colsurfb.2023.113189. Epub 2023 Feb 1.
Biomanufacturing of functional tissue analogues is of great importance in regenerative medicine. However, this is still highly challenging due to extreme difficulties in recreating/recapitulating complicated anatomies of body tissues that have both well-defined three-dimensional (3D) multicellular organizations and bioactive nanofibrous extracellular matrix (ECM). In the current investigation, a biomanufacturing approach via concurrent emulsion electrospinning and coaxial cell electrospraying was developed, which could fabricate 3D nanofibrous multicellular constructs that resemble both the multicellular organizations and bioactive nanofibrous microenvironments of body tissues. In the proof-of-concept study, endothelial cells (ECs) and smooth muscle cells (SMCs) were placed in respective layers of multilayer-structured constructs. The two different construct layers consisted of nanofibers providing different topographies (randomly oriented nanofibers or aligned nanofibers) and contained different growth factors (vascular endothelial growth factor or platelet-derived growth factor). The ECs and SMCs in the different construct layers showed high cell densities (> 4 ×10 cells/cm after 4-day incubation) and high cell viabilities (> 95%). Owing to the contact guidance/stimulation by different fibrous topographies and sequential release of different growth factors, ECs and SMCs exhibited distinct morphologies (uniformly stretched plaque-shaped or directionally elongated) and displayed enhanced proliferative activities. Our biomanufacturing approach is shown to be effective and efficient in reconstituting/replicating cell-ECM organizations as well as their interactions similar to those in body tissues such as blood vessels, indicating the great promise to produce a range of tissue analogues with biomimetic structures and functions for modeling or regenerating body tissues.
生物制造功能组织类似物在再生医学中具有重要意义。然而，由于在重建/复制具有明确三维（3D）多细胞组织和生物活性纳米纤维细胞外基质（ECM）的身体组织的复杂解剖结构方面存在极端困难，这仍然具有很大的挑战性。在当前的研究中，开发了一种通过共乳液静电纺丝和同轴细胞静电喷射的生物制造方法，该方法可以制造类似于身体组织的多细胞组织和生物活性纳米纤维微环境的 3D 纳米纤维多细胞构建体。在概念验证研究中，内皮细胞（ECs）和平滑肌细胞（SMCs）被放置在多层结构构建体的各自层中。这两个不同的构造层由提供不同形貌（随机取向的纳米纤维或取向的纳米纤维）的纳米纤维组成，并包含不同的生长因子（血管内皮生长因子或血小板衍生生长因子）。不同构造层中的 ECs 和 SMCs 表现出高细胞密度（孵育 4 天后>4×10 个细胞/cm）和高细胞活力（>95%）。由于不同纤维形貌的接触指导/刺激和不同生长因子的顺序释放，ECs 和 SMCs 表现出不同的形态（均匀拉伸的斑块状或定向伸长），并显示出增强的增殖活性。我们的生物制造方法被证明在重建/复制细胞-ECM 组织及其相互作用方面是有效和高效的，类似于血管等身体组织，这表明有望生产一系列具有仿生结构和功能的组织类似物，用于模拟或再生身体组织。
