A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis

Abstract

Background The objective of this study was to assess the efficacy of intra-articular injections of hyaluronic acid (HA) and a novel, on-site conjugate of HA with autologous fibrinogen in platelet-rich plasma (HA-PRP) in a canine model of osteoarthritis (OA) Methods Twelve beagle dogs underwent a unilateral resection of the cranial cruciate ligament (CrCL) of the stifle joint. Clinical and radiographic signs of OA were confirmed in all dogs 8 weeks following CrCL resection and prior to treatment. The dogs were randomized into three groups: saline (n = 4), HA (n = 4), and HA-PRP (n = 4). Each dog received intra-articular injections of the respective substance into the affected joint at pre-determined time points. The dogs were assessed for adverse effects for 3 days after each injection and for lameness, pain, range of motion, kinetics, and radiographic OA severity prior to treatment and 3 months after injection. OA severity as determined by radiographic examination was not significantly different among the groups at any time point. The dogs were then humanely euthanatized and the stifle joint assessed by gross and histological examinations. Results Dogs treated with four weekly injections of HA or two biweekly injections of HA-PRP were significantly (p < 0.05) better than dogs treated with four weekly injections of saline at 2-, 4-, and 12-week time points based on a comfortable range of motion (CROM) and clinical lameness score. Gait analysis measuring symmetry and weight distribution on pressure sensor walkway showed significantly (p < 0.05) improved limb function for dogs treated with HA and HA-PRP compared with dogs treated with saline yet with better clinical outcome for the HA-PRP-treated group at 12 and 20 weeks follow-up. Gross and histological analysis of synovium and articular cartilage demonstrated significant (p < 0.05) improvement by both treatments groups compared to controls. There was however significantly (p < 0.05) less damage to the cartilage in the HA-PRP group compared to the HA-treated group. Conclusions These data suggest that while injection of HA and HA-PRP may be sufficient for short-term amelioration of the symptoms associated with OA, treatment with HA-PRP conjugates may be superior, providing significantly better long-term cartilage preservation.

Platelet-rich plasma therapy in dogs with bilateral hip osteoarthritis

“…Many scores in PG were significantly better than those of CG up to the +120d follow-up and, in the case of PSS, up to the last follow-up (+180d). A similar longlasting effect has been described in dogs treated with PRP for the management of hip dysplasia [29], but shorter periods are presented for stifle OA [23][24][25]. A possible reason for this wide range of reported efficacy results of IA PRP may be related to the fact that hip OA seems to be better compensated by animals when compared to OA in other joints [30].…”

“…Our results show that the IA administration of PRP can reduce pain levels and several scores of different CMIs in dogs with bilateral hip OA. Several reports present a positive effect of IA PRP in the management of canine OA, but many are based on a surgically induced model of OA [23][24][25]. In dogs with naturally occurring OA, IA platelet products have shown to be able to improve clinical signs at the 12-week evaluation post-treatment [26].…”

A novel approach for knee osteoarthritis using high molecular weight hyaluronic acid conjugated to plasma fibrinogen – interim findings of a double-blind clinical study

“…The effects of RegenoGel on pain and function demonstrated by the present analysis may be attributed to its protection and support of cartilage integrity, as observed in animal models of damage-induced OA [ 22 ]. Such effects were not observed following multiple injections of either low or high-molecular-weight HA.…”

“…Preclinical studies in murine, caprine and canine [ 22 ] models of damage-induced OA, comparing the efficacy of fibrin-HA to HA alone, showed a substantial decrease in cartilage degeneration with significant overall joint preservation only in animals treated with the fibrin-HA conjugate. In all of these models, a single injection of either Regenogel or Regenogel-OSP was enough to confer significant cartilage preservation that was not observed even following multiple HA injections suggesting a potential shift in the balance from an actively catabolic environment to an anabolic, potentially regenerative microenvironment [ 23 ].…”

Use of Autologous Leucocyte- and Platelet-Rich Plasma (L-PRP) in the Treatment of Aural Hematoma in Dogs

“…In recent years, multiple effects of PRP have been documented in vivo and in vitro in human and veterinary medicine. In dogs, clinical studies are focused on orthopedics uses [35][36][37][38][39] and in dermatology for the treatment of wounds [40] or skin ulcers with extensive tissue loss [41][42][43], chronic ulcers [44], surgically induced wounds [45][46][47][48], alopecia [49] and for antimicrobial effects in infected skin wounds [50]. The results of these studies have been variable which may reflect the lack of standardization of the methods for obtaining the PRP.…”