Abstract

The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma. We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously. We assessed the clinical outcomes through osteoarthritis outcome score (KOOS) and the inflammatory response by quantifying mesenchymal stem cells in synovial fluid. There was a significant pain reduction in the KOOS from baseline (61.55 ± 14.11) to week 24 (74.60 ± 19.19), after treatment (p = 0.008), in the secondary outcomes (symptoms, p = 0.004; ADL, p = 0.022; sport/rec., p = 0.017; QOL, p = 0.012), as well as VAS score (p < 0.001) and Lequesne Index (p = 0.008). The presence of mesenchymal stem cells in synovial fluid and colony-forming cells one week after treatment decreased substantially from 7.98 ± 8.21 MSC/μL to 4.04 ± 5.36 MSC/μL (p = 0.019) and from 601.75 ± 312.30 to 139.19 ± 123.61 (p = 0.012), respectively. Intra-articular injections combined with intraosseous infiltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial fluid, besides significantly improving knee joint function in patients with severe knee osteoarthritis. This trial is registered on EudraCT with the number 2013-003982-32.

Highlights

  • Knee osteoarthritis (KOA) is a mechanically induced, cytokine and enzyme-mediated disorder comprising different phases and phenotypes, with pain as the clinical hallmark of the disease [1]

  • The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma

  • We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously

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Summary

Introduction

Knee osteoarthritis (KOA) is a mechanically induced, cytokine and enzyme-mediated disorder comprising different phases and phenotypes, with pain as the clinical hallmark of the disease [1]. This diarthrodial joint is a complex biological system where articular cartilage (AC), an aneural and avascular tissue, lies functionally sandwiched between two highly vascularized and innervated tissues, namely, synovial membrane (SM), which produces synovial fluid (SF), and subchondral bone (SB), both endowed with heat receptors, chemoreceptors, and mechanoreceptors. In patients with severe OA, the subchondral bone undergoes changes which include microcracks and structural defects, vascularization of channels, nerve growth, and a progressive replacement of the subchondral marrow with fibroneurovascular mesenchymal tissue changes which underpin the increasingly recognized crosstalk and pathway for direct transport of growth factors such as transforming growth factor B (TGFβ) and nerve growth factor (NGF) and even for cells such as macrophages and MSCs between the subchondral bone and articular cartilage [7,8,9,10].

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