Polymerized-Type I Collagen Downregulates Inflammation and Improves Clinical Outcomes in Patients with Symptomatic Knee Osteoarthritis Following Arthroscopic Lavage: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

Abstract

Objectives. Polymerized-type I collagen (polymerized collagen) is a downmodulator of inflammation and cartilage regenerator biodrug. Aim. To evaluate the effect of intraarticular injections of polymerized collagen after arthroscopic lavage on inflammation and clinical improvement in patients with knee osteoarthritis (OA). Methods. Patients (n = 19) were treated with 6 intraarticular injections of 2 mL of polymerized collagen (n = 10) or 2 mL of placebo (n = 9) during 3 months. Followup was 3 months. The primary endpoints included Lequesne index, pain on a visual analogue scale (VAS), WOMAC, analgesic usage, the number of Tregs and proinflammatory/anti-inflammatory cytokine-expressing peripheral cells. Secondary outcomes were Likert score and drug evaluation. Clinical and immunological improvement was determined if the decrease in pain exceeds 20 mm on a VAS, 20% of clinical outcomes, and inflammatory parameters from baseline. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTXII) and erythrocyte sedimentation rate (ESR) were determined. Results. Polymerized collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0.05) from baseline versus polymerized collagen and versus placebo at 6 months on Lequesne index, VAS, ESR, Tregs IL-1β, and IL-10 peripheral-expressing cells. Urinary levels of CTXII were decreased 44% in polymerized collagen versus placebo. No differences were found on incidence of adverse events between groups. Conclusion. Polymerized collagen is safe and effective on downregulation of inflammation in patients with knee OA.

Long-Term Effectiveness of Polymerized-Type I Collagen Intra-Articular Injections in Patients with Symptomatic Knee Osteoarthritis: Clinical and Radiographic Evaluation in a Cohort Study

“…In comparison, a study that evaluated the IAI effect of a high-molecular-weight hyaluronic preparation in knee OA reported a 67% knee survival rate (absence of TKR) at 60 months [36]. Our results suggest that polymerized-type I collagen is able to control the relief of symptoms and may act as disease-modifying OA drug that could slow or halt the radiographic evolution of the disease and prevent tissue damage [18][19][20][21]. Further RCTs with specific clinical or radiological endpoints are necessary to confirm these data.…”

“…For some years, our research group has focused on the effect of modified extracellular matrix proteins on the regulation of inflammation [13][14][15][16][17][18][19][20][21][22][23]. Particularly, polymerized-type I collagen is a c-irradiated mixture of pepsinized porcine type I collagen and polyvinylpyrrolidone.…”

“…The addition of 1% polymerized-type I collagen to cocultures of OA cartilage and synovial tissue induces cartilage regeneration due to a 3- to 6-fold increase in chondrocyte proliferation (Ki-67), proteoglycans, cartilage oligomeric matrix protein (COMP), and type II collagen [ 18 ]. Polymerized-type I collagen induces the downregulation of inflammation-inhibiting proinflammatory cytokine expression (IL-1 β and TNF- α ) through the modulation of NF- k B activation [ 15 , 20 ]. In addition, polymerized-type I collagen downregulates the circulating number of Th22, Th17, and Th1 cells and upregulates IL-10 expression and the circulating number of regulatory T, B, and plasmacytoid dendritic cells [ 15 , 18 , 20 ], unpublished observations .…”

“…Polymerized-type I collagen induces the downregulation of inflammation-inhibiting proinflammatory cytokine expression (IL-1 β and TNF- α ) through the modulation of NF- k B activation [ 15 , 20 ]. In addition, polymerized-type I collagen downregulates the circulating number of Th22, Th17, and Th1 cells and upregulates IL-10 expression and the circulating number of regulatory T, B, and plasmacytoid dendritic cells [ 15 , 18 , 20 ], unpublished observations .…”

Hyaluronic acid in the management of osteoarthritis: injection therapies innovations

“…Intra-articular (IA) injections represent a therapy that is often used in the management of OA to deliver the therapeutic agent directly into the joint space. IA injection therapies seems to have a good safety profile and several products can be used (6), including steroids (7)(8)(9)(10), hyaluronic acid (HA) (11,12), platelet-rich plasma (PRP) (13) and polymerized collagen (14). Viscosupplementation (VS) with IA-HA represents a well-established treatment option especially in knee OA and it is included in the medical guidelines for treatment of the disease in this joint, but it could be applied, theoretically, to all synovial joints in order to reduce pain, improve joint function and delay joint damage.…”