Zhao Xia, Hu Daniel A, Wu Di, He Fang, Wang Hao, Huang Linjuan, Shi Deyao, Liu Qing, Ni Na, Pakvasa Mikhail, Zhang Yongtao, Fu Kai, Qin Kevin H, Li Alexander J, Hagag Ofir, Wang Eric J, Sabharwal Maya, Wagstaff William, Reid Russell R, Lee Michael J, Wolf Jennifer Moriatis, El Dafrawy Mostafa, Hynes Kelly, Strelzow Jason, Ho Sherwin H, He Tong-Chuan, Athiviraham Aravind
Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States.
Front Bioeng Biotechnol. 2021 Mar 25;9:603444. doi: 10.3389/fbioe.2021.603444. eCollection 2021.
Cartilage, especially articular cartilage, is a unique connective tissue consisting of chondrocytes and cartilage matrix that covers the surface of joints. It plays a critical role in maintaining joint durability and mobility by providing nearly frictionless articulation for mechanical load transmission between joints. Damage to the articular cartilage frequently results from sport-related injuries, systemic diseases, degeneration, trauma, or tumors. Failure to treat impaired cartilage may lead to osteoarthritis, affecting more than 25% of the adult population globally. Articular cartilage has a very low intrinsic self-repair capacity due to the limited proliferative ability of adult chondrocytes, lack of vascularization and innervation, slow matrix turnover, and low supply of progenitor cells. Furthermore, articular chondrocytes are encapsulated in low-nutrient, low-oxygen environment. While cartilage restoration techniques such as osteochondral transplantation, autologous chondrocyte implantation (ACI), and microfracture have been used to repair certain cartilage defects, the clinical outcomes are often mixed and undesirable. Cartilage tissue engineering (CTE) may hold promise to facilitate cartilage repair. Ideally, the prerequisites for successful CTE should include the use of effective chondrogenic factors, an ample supply of chondrogenic progenitors, and the employment of cell-friendly, biocompatible scaffold materials. Significant progress has been made on the above three fronts in past decade, which has been further facilitated by the advent of 3D bio-printing. In this review, we briefly discuss potential sources of chondrogenic progenitors. We then primarily focus on currently available chondrocyte-friendly scaffold materials, along with 3D bioprinting techniques, for their potential roles in effective CTE. It is hoped that this review will serve as a primer to bring cartilage biologists, synthetic chemists, biomechanical engineers, and 3D-bioprinting technologists together to expedite CTE process for eventual clinical applications.
软骨,尤其是关节软骨,是一种独特的结缔组织,由软骨细胞和覆盖关节表面的软骨基质组成。它通过为关节之间的机械负荷传递提供几乎无摩擦的关节连接,在维持关节的耐久性和灵活性方面发挥着关键作用。关节软骨损伤常由运动相关损伤、全身性疾病、退变、创伤或肿瘤引起。未能治疗受损的软骨可能导致骨关节炎,影响全球超过25%的成年人口。由于成年软骨细胞增殖能力有限、缺乏血管化和神经支配、基质更新缓慢以及祖细胞供应不足,关节软骨的内在自我修复能力非常低。此外,关节软骨细胞被包裹在低营养、低氧的环境中。虽然软骨修复技术,如骨软骨移植、自体软骨细胞植入(ACI)和微骨折,已被用于修复某些软骨缺损,但临床结果往往参差不齐且不尽人意。软骨组织工程(CTE)可能有望促进软骨修复。理想情况下,成功的CTE的先决条件应包括使用有效的软骨生成因子、充足的软骨生成祖细胞供应以及使用对细胞友好、生物相容的支架材料。在过去十年中,在上述三个方面都取得了重大进展,3D生物打印的出现进一步推动了这些进展。在这篇综述中,我们简要讨论软骨生成祖细胞的潜在来源。然后,我们主要关注目前可用的对软骨细胞友好的支架材料以及3D生物打印技术,探讨它们在有效的CTE中的潜在作用。希望这篇综述能作为一个入门指南,将软骨生物学家、合成化学家、生物力学工程师和3D生物打印技术专家聚集在一起,加快CTE进程,最终实现临床应用。