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.
Auricular cartilage reconstruction represents one of the greatest challenges for otolaryngology–head and neck surgery. The native structure and composition of the auricular cartilage can be achieved by combining a suitable chondrogenic cell source with an appropriate scaffold. In reconstructive surgery for cartilage tissue, autogenous cartilage is considered to be the best chondrogenic cell source. Polycaprolactone is mainly used as a tissue-engineered scaffold owing to its mechanical properties, miscibility with a large range of other polymers, and biodegradability. In this study, scaffolds with or without autogenous minced auricular cartilage were implanted bilaterally in rabbits for auricular regeneration. Six weeks (n = 4) and 16 weeks (n = 4) after implantation, real-time quantitative reverse transcription polymerase chain reaction and histology were used to assess the regeneration of the auricular cartilage. Quantitative reverse transcription polymerase chain reaction analysis revealed that the messenger RNA expression of aggrecan, collagen I, and collagen II was higher in scaffolds with 50% minced cartilage than the scaffold-only groups or scaffolds with 30% minced cartilage (P < 0.05). Furthermore, histological analysis demonstrated significantly superior cartilage regeneration in scaffolds with the minced cartilage group compared with the scaffold-only and control groups (P < 0.05). Autogenous cartilage can be easily obtained and loaded onto a scaffold to promote the presence of chondrogenic cells, allowing for an improvement of the reconstruction of auricular cartilage. Here, the regeneration of auricular cartilage was also successful in the 50% minced cartilage group. The results presented in this study could have clinical implications, as they demonstrate the potential of a 1-stage process for auricular reconstruction.
Background: The treatments of osteoarthritis (OA) are commonly conservative and multimodal to relieve pain and improve movement. Intra-articular injection of hyaluronic acid (IAHA) has been studied as a treatment option for OA in dogs. IAHA helps restore the viscoelasticity of the synovial fluid and relieves the clinical symptoms of OA. However, the efficacy of IAHA in dogs is still a controversial subject. This study aims to confirm the IAHA effect in dogs with spontaneous OA and to compare the effectiveness depending on the number of injections. Materials, Methods & Results: Thirty dogs with spontaneous OA were assigned to a single injection group (n=17) and a 3-weekly injections group (n=13). Dogs weighing less than 10 kg were injected 1 mL of HA to the OA joint, and more than 10 kg dogs were injected 2 mL of HA. In the case of the 3-weekly injections group, the same amount was administered 3 times at 1-week intervals. After the injection, physical and orthopedic examinations were performed to check for complications. Radiographic OA score was evaluated before and 3 months after the injection to confirm and to evaluate the progression of OA. Clinical symptom evaluations were performed on pre-injection, 1-, 2-, and 3-months post-injection. They consisted of the clinical lameness score by veterinarians and Canine Brief Pain Inventory (CBPI) by owners. Results were compared with unpaired t-test, repeated-measures ANOVA with Tukey’s or Sidak’s multiple comparison test, or Wilcoxon test, with P < 0.05. Patients had a median age of 9 years (range 3 to 16 years) and a bodyweight of 4.8 kg (range 2 to 48 kg). No systemic side effects or major complications were detected during the trial period. IAHA produced temporary pain and discomfort in 6 cases. There was no change in the radiographic OA score before and 3 months after injections in both groups, and the difference between groups was not confirmed. In both groups, the clinical lameness score significantly decreased at 1, 2, 3 months after injection compared with pre-injection. The score was lower at 3 months after the injection than at 1 month. The clinical lameness score had no significant difference between the groups. Similarly, CBPI was all decreased in the single injection group and 3-weekly injections group compared to pre-injection, and the score at 3 months post-injection was lower than at 1 month. No significant differences between the groups were found in CBPI. Discussion: Most studies on the efficacy of IAHA in canine OA have been conducted using an experimental model, so studies on spontaneous canine OA are insufficient. This study confirmed that IAHA improves clinical symptoms such as pain relief and movement improvement in spontaneous OA dogs using CBPI and clinical lameness score. In order to confirm the optimal IAHA protocol, a single IAHA and 3-weekly IAHA were compared. The result shows that clinical symptoms improved in both single and 3-weekly injections groups, but no significant difference was confirmed during the 3-month study period. These findings may suggest that a single IAHA may have a similar effect to multiple IAHA, and repeated injections are unnecessary. In humans and canine OA models, it is reported that the effect of IAHA was maintained for 6 months. This study showed that the effect of IAHA was maintained for 3 months study period and that clinical symptoms improved at 3 months than at 1 month. In conclusion, these findings suggested that IAHA improves clinical symptoms in dogs with spontaneous OA, and a single IAHA showed a similar effect to 3 weekly IAHA.
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