Combination of a Collagen Scaffold and an Adhesive Hyaluronan-Based Hydrogel for Cartilage Regeneration: A Proof of Concept in an Ovine Model

Objective Hyaluronic acid–transglutaminase (HA-TG) is an enzymatically crosslinkable adhesive hydrogel with chondrogenic properties demonstrated in vitro and in an ectopic mouse model. In this study, we investigated the feasibility of using HA-TG in a collagen scaffold to treat chondral lesions in an ovine model, to evaluate cartilage regeneration in a mechanically and biologically challenging joint environment, and the influence of the surgical procedure on the repair process. Design Chondral defects of 6-mm diameter were created in the stifle joint of skeletally mature sheep. In a 3-month study, 6 defects were treated with HA-TG in a collagen scaffold to test the stability and biocompatibility of the defect filling. In a 6-month study, 6 sheep had 12 defects treated with HA-TG and collagen and 2 sheep had 4 untreated defects. Histologically observed quality of repair tissue and adjacent cartilage was semiquantitatively assessed. Results HA-TG adhered to the native tissue and did not cause any detectable negative reaction in the surrounding tissue. HA-TG in a collagen scaffold supported infiltration and chondrogenic differentiation of mesenchymal cells, which migrated from the subchondral bone through the calcified cartilage layer. Additionally, HA-TG and collagen treatment led to better adjacent cartilage preservation compared with empty defects ( P < 0.05). Conclusions This study demonstrates that the adhesive HA-TG hydrogel in a collagen scaffold shows good biocompatibility, supports in situ cartilage regeneration and preserves the surrounding cartilage. This proof-of-concept study shows the potential of this approach, which should be further considered in the treatment of cartilage lesions using a single-step procedure.

Small-Diameter Subchondral Drilling Improves DNA and Proteoglycan Content of the Cartilaginous Repair Tissue in a Large Animal Model of a Full-Thickness Chondral Defect

This study quantified changes in the DNA content and extracellular matrix composition of both the cartilaginous repair tissue and the adjacent cartilage in a large animal model of a chondral defect treated by subchondral drilling. Content of DNA, proteoglycans, and Type II and Type I collagen, as well as their different ratios were assessed at 6 months in vivo after treatment of full-thickness cartilage defects in the femoral trochlea of adult sheep with six subchondral drill holes, each of either 1.0 mm or 1.8 mm in diameter by biochemical analyses of the repair tissue and the adjacent cartilage and compared with the original cartilage. Only subchondral drilling which were 1.0 mm in diameter significantly increased both DNA and proteoglycan content of the repair tissue compared to the original cartilage. DNA content correlated with the proteoglycan and Type II collagen content within the repair tissue. Significantly higher amounts of Type I collagen within the repair tissue and significantly increased DNA, proteoglycan, and Type I collagen content in the adjacent cartilage were identified. These translational data support the use of small-diameter bone-cutting devices for marrow stimulation. Signs of early degeneration were present within the cartilaginous repair tissue and the adjacent cartilage.

Surgical dislocation of the hip in patients with femoroacetabular impingement: Surgical techniques and our experience

Background/Aim. Arthrosis of the hip is the most common cause of a hip joint disorders. The aim of this study was to present our experience in the application of a safe surgical dislocation of the hip in patients with minor morphological changes in the hip joint, which, through the mechanism of femoroacetabular impingement, cause damage to the acetabular labrum and adjacent cartilage as an early sign of the hip arthrosis. Methods. We have operated 51 patients with different morphological bone changes in the hip area and resultant soft tissue damage of the acetabular labrum and its adjacent cartilage. Surgical technique that we applied in this group of patients, was adapted to our needs and capabilities and it was minimaly modified compared to the original procedure. Results. The surgical technique presented in this paper, proved to be a good method of treatment of bone and soft tissue pathomorphological changes of the hip in patients with femoroacetabular impingement. We had no cases with avascular necrosis of the femoral head, and two patients had nonunion of the greater trochanter, 9 patients developed paraarticular ossification, without subjective symptoms, while 3 patients suffered from postoperative pain in the groin during more energetic physical activities. Conclusion. Utilization of our partly modified surgical technique of controlled and safe dislocation of the hip can solve all the bone and soft tissue problems in patients with femoroacetibular impingement to stop already developed osteoarthritis of the hip or to prevent mild form of it.

The Clinical Outcomes of Anterior Cruciate Ligament Reconstruction Surgery Based on Iatrogenic Damage

Objectives: To examine the degenerative changes of adjacent cartilage and bony structure, after anterior cruciate ligament reconstruction surgery. Methods: 27 subjects, who had anterior cruciate ligament reconstruction surgery due to various reasons at least 12 months ago, were admitted to study. MRI data of patients were acquired retrospectively. Pre-operative and post-operative MRI images were compared according to retropatellar cartilage thickness, evidence of any new osteophytes formation or any signal intensity change on bony elements. Paired statistical analysis was applied. Results: The MRI revelation showed that; there were 14 patients with decrement of retropatellar cartilage thickness, 9 patients with new osteophytes formation and 21 patients with abnormal signal intensity change on bony elements; which were statistically significant (P<0.001). Conclusion: These results provide basic information about the degenerative effect of anterior cruciate ligament reconstruction surgery, on adjacent cartilage and bony structure.

Transcutaneous Treatment with Vetdrop® Sustains the Adjacent Cartilage in a Microfracturing Joint Defect Model in Sheep

The significance of the adjacent cartilage in cartilage defect healing is not yet completely understood. Furthermore, it is unknown if the adjacent cartilage can somehow be influenced into responding after cartilage damage. The present study was undertaken to investigate whether the adjacent cartilage can be better sustained after microfracturing in a cartilage defect model in the stifle joint of sheep using a transcutaneous treatment concept (Vetdrop®). Carprofen and chito-oligosaccharids were added either as single components or as a mixture to a vehicle suspension consisting of a herbal carrier oil in a water-in-oil phase. This mixture was administered onto the skin with the aid of a specific applicator during 6 weeks in 28 sheep, allocated into 6 different groups, that underwent microfracturing surgery either on the left or the right medial femoral condyle. Two groups served as control and were either treated intravenously or sham treated with oxygen only. Sheep were sacrificed and their medial condyle histologically evaluated qualitatively and semi-quantitatively according to 4 different scoring systems (Mankin, ICRS, Little and O’Driscoll). The adjacent cartilage of animals of group 4 treated transcutaneously with vehicle, chito-oligosaccharids and carprofen had better histological scores compared to all the other groups (Mankin 3.3±0.8, ICRS 15.7±0.7, Little 9.0±1.4). Complete defect filling was absent from the transcutaneous treatment groups. The experiment suggests that the adjacent cartilage is susceptible to treatment and that the combination of vehicle, chitooligosaccharids and carprofen may sustain the adjacent cartilage during the recovery period.