Department of Biomedical Engineering, University of Groningen, University Medical Center Groningen, FB40, Antonius Deusinglaan -1, 9713AV, Groningen, The Netherlands.
Department of Orthopedics, University Medical Center Groningen, Groningen, The Netherlands.
Tissue Eng Regen Med. 2023 Dec;20(7):1041-1052. doi: 10.1007/s13770-023-00573-6. Epub 2023 Oct 20.
Osteoarthritis (OA) is the most common degenerative joint disease without an ultimate treatment. In a search for novel approaches, tissue engineering (TE) has shown great potential to be an effective way for hyaline cartilage regeneration and repair in advanced stages of OA. Recently, induced pluripotent stem cells (iPSCs) have been appointed to be essential stem cells for degenerative disease treatment because they allow a personalized medicine approach. For clinical translation, bioreactors in combination with iPSCs-engineerd cartilage could match patients needs, serve as platform for large-scale patient specific cartilage production, and be a tool for patient OA modelling and drug screening. Furthermore, to minimize in vivo experiments and improve cell differentiation and cartilage extracellular matrix (ECM) deposition, TE combines existing approaches with bioreactors.
This review summarizes the current understanding of bioreactors and the necessary parameters when they are intended for cartilage TE, focusing on the potential use of iPSCs.
Bioreactors intended for cartilage TE must resemble the joint cavity niche. However, recreating human synovial joints is not trivial because the interactions between various stimuli are not entirely understood.
The use of mechanical and electrical stimulation to differentiate iPSCs, and maintain and test chondrocytes are key stimuli influencing hyaline cartilage homeostasis. Incorporating these stimuli to bioreactors can positively impact cartilage TE approaches and their possibility for posterior translation into the clinics.
骨关节炎（OA）是最常见的退行性关节疾病，目前尚无根治方法。在寻求新方法的过程中，组织工程（TE）显示出了巨大的潜力，可以有效地再生和修复 OA 的晚期透明软骨。最近，诱导多能干细胞（iPSCs）被认为是治疗退行性疾病的重要干细胞，因为它们可以实现个体化医疗。为了临床转化，生物反应器与 iPSCs 工程软骨相结合，可以满足患者的需求，成为大规模患者特异性软骨生产的平台，并可用于患者 OA 建模和药物筛选。此外，为了减少体内实验并提高细胞分化和软骨细胞外基质（ECM）沉积，TE 将现有的方法与生物反应器结合使用。
本文综述了生物反应器的当前研究进展，以及其在软骨 TE 中的应用所必需的参数，重点介绍了 iPSCs 的潜在用途。
用于软骨 TE 的生物反应器必须类似于关节腔微环境。然而，由于各种刺激因素之间的相互作用尚未完全了解，因此重建人类滑膜关节并非易事。
机械和电刺激用于 iPSCs 的分化，以及维持和测试软骨细胞，是影响透明软骨稳态的关键刺激因素。将这些刺激因素纳入生物反应器可以对软骨 TE 方法及其在临床上的后续转化产生积极影响。
