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Review
. 2023 Apr 27;11(4):23259671231155950.
doi: 10.1177/23259671231155950. eCollection 2023 Apr.

A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections

Nicholas A Householder  1 , Akshay Raghuram  1 , Kofi Agyare  1 , Skyler Thipaphay  1 , Mimi Zumwalt  1
Affiliations
Review

A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections

Nicholas A Householder et al. Orthop J Sports Med. .

Abstract

Background: 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.

Purpose: 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.

Study design: Narrative review.

Methods: 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.

Conclusion: 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.

Keywords: articular cartilage; injections; osteoarthritis; regeneration.

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Conflict of interest statement

The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Figures

Figure 1.
Figure 1.
Flowchart of factors involved in primary osteoarthritis.
See this image and copyright information in PMC

References

    1. Aini H, Itaka K, Fujisawa A, et al.Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. Sci Rep. 2016;6:18743. - PMC - PubMed
    1. Bąkowski P, Kaszyński J, Wałecka J, et al.Autologous adipose tissue injection versus platelet-rich plasma (PRP) injection in the treatment of knee osteoarthritis: a randomized, controlled study—study protocol. BMC Musculoskelet Disord. 2020;21(1):314. - PMC - PubMed
    1. Barnes PJ.How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006;148(3):245–254. - PMC - PubMed
    1. Basic bone biology. Medtronic Sofamor Danek; 2002. https://www.healio.com/news/orthopedics/20120331/etiology-and-pathophysi...
    1. Bastos R, Mathias M, Andrade R, et al.Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018;26(11):3342–3350. - PubMed

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