Householder Nicholas A, Raghuram Akshay, Agyare Kofi, Thipaphay Skyler, Zumwalt Mimi
School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Orthop J Sports Med. 2023 Apr 27;11(4):23259671231155950. doi: 10.1177/23259671231155950. eCollection 2023 Apr.
The pathology of primary osteoarthritis (OA) begins with structural cartilage damage, which initiates a self-propagating inflammatory pathway that further exacerbates cartilage deterioration. Current standard of care for knee primary OA involves treating the inflammatory symptoms to manage pain, which includes intra-articular (IA) injections of cortisone, an anti-inflammatory steroid, followed by a series of joint-cushioning hyaluronic acid gel injections. However, these injections do not delay the progression of primary OA. More focus on the underlying cellular pathology of OA has prompted researchers to develop treatments targeting the biochemical mechanisms of cartilage degradation.
Researchers have yet to develop a United States Food and Drug Administration (FDA)-approved injection that has been demonstrated to significantly regenerate damaged articular cartilage. This paper reviews the current research on experimental injections aimed at achieving cellular restoration of the hyaline cartilage tissue of the knee joint.
Narrative review.
The authors conducted a narrative literature review examining studies on primary OA pathogenesis and a systematic review of non-FDA-approved IA injections for the treatment of primary OA of the knee, described as "disease-modifying osteoarthritis drugs" in phase 1, 2, and 3 clinical trials.
New treatment approaches for primary OA investigate the potential of genetic therapies to restore native cartilage. It is clear that the most promising IA injections that could improve treatment of primary OA are bioengineered advanced-delivery steroid-hydrogel preparations, ex vivo expanded allogeneic stem cell injections, genetically engineered chondrocyte injections, recombinant fibroblast growth factor therapy, injections of selective proteinase inhibitors, senolytic therapy via injections, injectable antioxidant therapies, injections of Wnt pathway inhibitors, injections of nuclear factor-kappa β inhibitors, injections of modified human angiopoietin-like-3, various potential viral vector-based genetic therapy approaches, and RNA genetic technology administered via injections.
原发性骨关节炎（OA）的病理始于结构性软骨损伤，这会引发一种自我传播的炎症途径，进一步加剧软骨退化。目前膝关节原发性OA的标准治疗方法包括治疗炎症症状以控制疼痛，其中包括关节内（IA）注射皮质醇（一种抗炎类固醇），随后进行一系列关节缓冲透明质酸凝胶注射。然而，这些注射并不能延缓原发性OA的进展。对OA潜在细胞病理学的更多关注促使研究人员开发针对软骨降解生化机制的治疗方法。
研究人员尚未开发出一种经美国食品药品监督管理局（FDA）批准的、已被证明能显著再生受损关节软骨的注射剂。本文综述了目前关于旨在实现膝关节透明软骨组织细胞修复的实验性注射剂的研究。
叙述性综述。
作者进行了一项叙述性文献综述，研究原发性OA的发病机制，并对在1期、2期和3期临床试验中被描述为“疾病修饰性骨关节炎药物”的非FDA批准的IA注射剂治疗膝关节原发性OA进行了系统综述。
原发性OA的新治疗方法正在研究基因疗法恢复天然软骨的潜力。显然，最有前景的可改善原发性OA治疗的IA注射剂包括生物工程先进递送类固醇 - 水凝胶制剂、体外扩增的同种异体干细胞注射剂、基因工程软骨细胞注射剂、重组成纤维细胞生长因子疗法、选择性蛋白酶抑制剂注射剂、注射溶细胞疗法、可注射抗氧化剂疗法、Wnt途径抑制剂注射剂、核因子 - κβ抑制剂注射剂、修饰的人血管生成素样 - 3注射剂、各种潜在的基于病毒载体的基因治疗方法以及通过注射给药的RNA基因技术。
