Treatment Of Local Cartilage Defects Research Articles

Collagen-Covered Autologous Chondrocyte Implantation Versus Autologous Matrix-Induced Chondrogenesis: A Randomized Trial Comparing 2 Methods for Repair of Cartilage Defects of the Knee.

Background:Autologous matrix-induced chondrogenesis (AMIC) is a single-stage alternative to autologous chondrocyte implantation for treatment of localized cartilage defects of the knee. To our knowledge, no randomized controlled trial exists comparing the 2 methods.Purpose:To evaluate any difference in the outcome of AMIC as compared with collagen-covered autologous chondrocyte implantation (ACI-C).Study Design:Randomized controlled trial; Level of evidence, 2.Methods:A prospective randomized controlled clinical trial was designed to assess any differences in the outcomes between ACI-C and AMIC for the treatment of ≥1 chondral or osteochondral defects of the distal femur and/or patella. The inclusion period was set to 3 years, and the aim was to include 80 patients (40 in each group). Patient inclusion was broad, with few exclusion criteria. The primary outcome was change in Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 years as compared with baseline. The secondary outcomes were the number of failures in each group at 2 years and the change in KOOS subscale, Lysholm, and pain visual analog scale (VAS) scores at 2 years as compared with baseline. A 2-sample t test with a significance level of P < .05 was used to compare the change in score from baseline between groups.Results:A total of 41 patients over 3 years were included in the study: 21 in the ACI-C group and 20 in the AMIC group. All the patients had prior surgery to the index knee. At 2-year follow-up, the clinical scores for both groups improved significantly from baseline. No significant differences between groups were seen in the change from baseline for KOOS (AMIC, 18.1; ACI-C, 10.3), any of the KOOS subscales, the Lysholm score (AMIC, 19.7; ACI-C, 17.0), or the VAS pain score (AMIC, 30.6; ACI-C, 19.6). Two patients in the AMIC group had progressed to a total knee replacement by the 2-year follow-up as compared with none in the ACI-C group.Conclusion:At 2-year follow-up, no significant differences were found regarding outcomes between ACI-C and AMIC. Mid- and long-term results will be important.Registration:NCT01458782 (ClinicalTrials.gov identifier).

Focal metallic inlay resurfacing prosthesis for the treatment of localized cartilage defects of the femoral condyles: a systematic review of clinical studies.

To systematically review the results of focal metallic inlay resurfacing prosthesis for the treatment of isolated cartilage defects of the femoral condyles. A systematic electronic search of the PubMed database and the Cochrane Library was performed in April 2017 to identify studies that reported clinical or radiographic outcome of focal metallic inlay resurfacing prosthesis for the treatment of isolated cartilage defects of the femoral condyles. Included studies were abstracted regarding study characteristics, patient demographics, prosthetic device and location, indications and contraindications, and outcome measures. Outcome of interest included functional outcome scores, radiographic measures, complications, re-operations, and conversion to arthroplasty. The methodologic quality of the included studies was assessed with the Coleman Methodology Score. Six studies with a total of 186 patients met the inclusion criteria. Five studies were level IV evidence, and one was level III. The methodologic quality of the included studies was good, with a mean Coleman Methodology Score of 78. Two different implants were used: the HemiCAP® (five studies; 66% of study group) and UniCAP® (one study; 34%) implant. The mean age was 46-54years, and the mean follow-up was 24months to 7years. Pre- and post-operative outcome scores were compared in all six studies, and five studies reported significant improvements at the final follow-up for all scores (objective und functional KSS, KOOS, WOMAC, Tegner, HSS Knee and Function score, SF-36 and SF-12 physical component score) except for the SF-36 and SF-12 mental component score. Progression of osteoarthritis was analysed using the Kellgren-Lawrence grading in three studies (30% of study group), with two studies reporting significant progression. The OARSI grading system was analysed in one study with no significant progression. The overall conversion rate to arthroplasty was 22% with considerable differences between the two implants: 9% for HemiCAP® and 47% for UniCAP®. Focal metallic inlay resurfacing prosthesis seems to be a viable option for a carefully selected group of patients. Significant improvement in knee function and pain was observed in most patients. Uncertainty remains with regard to progression of osteoarthritis because of conflicting results and inconsistent reporting. One out of five patients has to be converted to arthroplasty after an average of 4years. However, compared to the UniCAP® implant, considerable lower conversion rates were reported for the smaller HemiCAP® implant. Systematic review of level III and IV studies, Level IV.

The outcome of the partial resurfacing arthroplasty of the hip shows high numbers of failures and conversion to total arthroplasty.

Local cartilage and bony defects, which are too large for joint preserving cartilage treatment are difficult to treat. The implantation of a mini-resurfacing implant (Hemicap®, 2med, Hamburg, Germany) may be a possible alternative treatment for these patients. This partial replacement fills the defect and restores a smooth and continuous articular surface. The aim of this study was to determine short- to midterm results of the treatment of local cartilage defects of the femoral head using the Hemicap®. Since 04/2011 16 patients with osteonecrosis of the femoral head greater ARCO stage II or local femoral cartilage lesions (< 35mm) were treated with the implantation of the Hemicap® implant. A clinical and radiological follow-up was conducted. The clinical results showed a significant improvement of the function and pain of the hip according to the Harris Hip Score from 56 (±14) preoperative to 77 (±15) post-operative 25months after implantation of the Hemicap®. In the meantime, in four patients the Hemicap® had to be converted to a total hip arthroplasty due to loosening, progredience of the osteonecrosis or degeneration of the acetabulum. The implantation of the mini-resurfacing implant Hemicap® seemed to be an alternative treatment for local cartilage defects of the femoral head to postpone the implantation of a total hip arthroplasty. However, the clinical outcome seems to be inferior to total hip arthroplasty. Furthermore, due to a high rate of conversion to total hip arthroplasty (25%) the application of this implant is questionable. If the implant is considered as a treatment option at least patient selection and enlightenment for this treatment with the high risk of failure and progression of osteoarthritis is very important.

Matrix-Associated Autologous Chondrocyte Implantation: A Clinical Follow-Up at 15 Years.

A prospective clinical investigation was carried out in order to clarify whether Matrix-associated autologous chondrocyte implantation (MACI) results in clinical improvement at long-term follow-up. MACI will result in clinical improvement at long-term follow-up. Case series; level of evidence, 4. Thirty-eight patients were treated with MACI. These patients were evaluated for up to a mean of 16 years (range 15-17 years) after the intervention. Three different scores (Lysholm-Gilquist score, International Cartilage Repair Society score, and Tegner score) formed the basis of this study. Overall, we were able to obtain valid preoperative and postoperative results from 18 (47%) of 38 patients. In 1 patient, both knees were treated. In 4 patients, an arthroplasty was implanted over the course of time; thus they were excluded from this case series. In conclusion, follow-up of 15 knees was performed in the recent series. In subjective rating, 12 out of 14 patients (86%) rated the function of their knee as much better or better than before the index procedure. All numerical outcome scores showed significant improvement compared to the preoperative value (preoperative/postoperative at 5 years/postoperative at 15 years): Lysholm score 59.6 (±24.6)/78.6 (±21.5)/82.7 (±11.3), International Knee Documentation Committee score 50.6 (±22.7)/64.7 (±21.6)/69.7 (±18.7), Tegner score 3.0 (±2.2)/3.6 (±1.5)/5.2 (±1.7). The significantly improved results on 3 scores after 15 years suggest that MACI represents a suitable treatment of local cartilage defects in the knee.

Clinical and Radiological Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Transplantation

Background: It is unclear whether matrix-associated autologous chondrocyte transplantation (MACT) results in objective and subjective clinical improvements at 10 years after surgery. Hypothesis: Matrix-associated autologous chondrocyte transplantation will result in clinical and radiological improvements in patients with symptomatic, traumatic chondral defects of the knee joint. Study Design: Case series; Level of evidence, 4. Methods: A total of 16 patients with chondral defects of the knee were treated with MACT between November 2000 and April 2002 and evaluated for up to 10 years after the intervention. The International Knee Documentation Committee (IKDC) form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Brittberg score, Noyes sports activity rating scale, and visual analog scale (VAS) for pain as well as 3-T magnetic resonance imaging (MRI) using the magnetic resonance observation of cartilage repair tissue (MOCART) score and functional evaluation by the limb symmetry index (LSI) formed the basis of this study. The Friedman test and the Wilcoxon signed-rank test were performed for a comparison between all time points and 2 separate time points, respectively. If significant differences were revealed, a Bonferroni adjustment to the α level was applied so that P values <.007 (<.05/7) were regarded as significant in the paired comparisons. Results: Significant improvements (P < .05) from baseline to 120 months postoperatively were observed for the IKDC score (mean, 44.1 ± 26.9 to 59.0 ± 27.4), Noyes sports activity rating score (mean, 37.7 ± 30.1 to 62.1 ± 31.3), and KOOS Quality of Life and Pain subscores, whereas no statistically significant improvement was detected for the Brittberg score, Tegner activity score, or VAS score. After 5 years, a slight downward tendency of all clinical scores was evident. After 10 years, the mean MOCART score was 70.4 ± 16.1. Complete filling of the defect was observed in 73.9% of cases, and osteophytes were present in 78.3%. In 65.2% of the cases, a subchondral bone edema <1 cm was visible, whereas in 21.7% of the cases, a subchondral bone edema >1 cm was seen. The mean LSI for the single-legged hop test was 95.6% ± 16.2% and for the triple hop test for distance was 91.3% ± 12.2%. The mean VAS score for self-perceived stability was 60.2 ± 3.5 (range, 0-9.5) for the injured and 60.7 ± 3.8 (range, 0-10) for the uninjured leg. No adhesions or effusions were seen regarding the clinical and radiological outcomes. Conclusion: The significantly improved results on 3 outcome measures after 10 years suggest that MACT represents a suitable option in the treatment of local cartilage defects in the knee.

Synovial Membrane–Derived Mesenchymal Stem Cells Supported by Platelet-Rich Plasma Can Repair Osteochondral Defects in a Rabbit Model

The aim of this study was to determine the in vivo effectiveness of synovial membrane-derived mesenchymal stem cell (SDSC)-encapsulated injectable platelet-rich plasma (PRP) gel in the repair of damaged articular cartilage in the rabbit. An osteochondral defect was created in the trochlear groove of the rabbit femur, and the defects were divided into 3 treatment groups: untreated control group, PRP group, and PRP-SDSC group. After 4, 12, and 24 weeks, the tissue specimens were assessed by macroscopic examination and histologic evaluation and stained immunohistochemically for type II collagen and proliferating cell nuclear antigen. In addition, total glycosaminoglycan content was determined at 24 weeks. Rabbit PRP contained a high concentration of platelets and high concentration of growth factors compared with those in whole blood. Twenty-four weeks after transplantation, there was fibrous tissue in the control group. In both the PRP group and the PRP-SDSC group, the defects were repaired with hyaline cartilage and exhibited significantly higher safranin O staining, type II collagen immunostaining, glycosaminoglycan content, cumulative histologic scores, and number of proliferating cell nuclear antigen-positive cells. However, incomplete bone regeneration and irregular cartilage surface integration were observed in the PRP group. Our results indicate that SDSC-embedded PRP gel could successfully resurface the defect with cartilage and restore the subchondral bone in the rabbit model. This study indicates that in an animal model, the application of PRP and SDSC in combination for the treatment of local cartilage defects appears promising; however, PRP-SDSC products might be more or less appropriate to treat different types of tissues and pathologies. The clinical efficacy of PRP remains under debate. Therefore further research is needed at both the basic science and clinical levels.

Graft hypertrophy of matrix-based autologous chondrocyte implantation: a two-year follow-up study of NOVOCART 3D implantation in the knee

Graft hypertrophy is a major complication in the treatment for localized cartilage defects with autologous chondrocyte implantation (ACI) using periosteal flap and its further development, Novocart (a matrix-based ACI procedure). The aim of the present study is to investigate individual criteria for the development of graft hypertrophy by NOVOCART 3D implantation of the knee in the post-operative course of 2 years. Forty-one consecutive patients with 44 isolated cartilage defects of the knee were treated with NOVOCART 3D implants. Individual criteria and defect-associated criteria were collected. Follow-up MRIs were performed at 3, 6, 12 and 24 months. The NOVOCART 3D implants were measured and classified. The modified MOCART Score was used to evaluate quality and integration of the NOVOCART 3D implants in MRI. Graft hypertrophy was observed in a total of 11 patients at all post-operative time points. We were able to show that NOVOCART 3D implantation of cartilage defects after acute trauma and osteochondritis dissecans (OCD) led to a significantly increased proportion of graft hypertrophy. No other individual criteria (age, gender, BMI) or defect-associated criteria (concomitant surgery, second-line treatment, defect size, fixation technique) showed any influence on the development of graft hypertrophy. The modified MOCART Score results revealed a significant post-operative improvement within 2 years. The aetiology of cartilage defects appears to have a relevant influence for the development of graft hypertrophy. Patients, who were treated with NOVOCART 3D implants after an acute event (acute trauma or OCD), are especially at risk for developing a graft hypertrophy in the post-operative course of two years. Case series, Level IV.

The Role of Growth Factors in Cartilage Repair

Full-thickness chondral defects and early osteoarthritis continue to present major challenges for the patient and the orthopaedic surgeon as a result of the limited healing potential of articular cartilage. The use of bioactive growth factors is under consideration as a potential therapy to enhance healing of chondral injuries and modify the arthritic disease process. We reviewed the role of growth factors in articular cartilage repair and identified specific growth factors and combinations of growth factors that have the capacity to improve cartilage regeneration. Additionally, we discuss the potential use of platelet-rich plasma, autologous-conditioned serum, and bone marrow concentrate preparations as methods of combined growth factor delivery. A PubMed search was performed using key words cartilage or chondrocyte alone and in combination with growth factor. The search was open for original manuscripts and review papers and open for all dates. From these searches we selected manuscripts investigating the effects of growth factors on extracellular matrix synthesis and excluded those investigating molecular mechanisms of action. By modulating the local microenvironment, the anabolic and anticatabolic effects of a variety of growth factors have demonstrated potential in both in vitro and animal studies of cartilage injury and repair. Members of the transforming growth factor-β superfamily, fibroblast growth factor family, insulin-like growth factor-I, and platelet-derived growth factor have all been investigated as possible treatment augments in the management of chondral injuries and early arthritis. The application of growth factors in the treatment of local cartilage defects as well as osteoarthritis appears promising; however, further research is needed at both the basic science and clinical levels before routine application.

Cartilage degeneration in the goat knee caused by treating localized cartilage defects with metal implants

The purpose of the current study was to investigate the feasibility of applying defect-size femoral implants for the treatment of localized cartilage defects in a 1-year follow-up model. In 13 goats, a medial femoral condyle defect was created in both knees. Defects were randomly treated by immediate placement of an oxidized zirconium (OxZr) (n=9) or cobalt-chromium (CoCr) implant (n=9) or left untreated (n=8). Six un-operated knee joints served as a control. Animals were sacrificed at 52 weeks. Joints were evaluated macroscopically. Cartilage quality was analyzed macroscopically and microscopically and cartilage repair of untreated defects was scored microscopically. Glycosaminoglycan (GAG) content, release and synthesis were measured in tissue and medium. Implant osseointegration was measured by automated histomorphometry. Cartilage repair score of the defects was 13.3+/-3.0 out of 24 points (0=no repair, 24=maximal repair). Articular evaluation scores decreased (indicative of degeneration) in untreated defects and in defects treated with either implant (P<0.05). Macroscopical, microscopical and biochemical analysis showed that the presence of untreated defects and the implants caused considerable degeneration of medial tibial plateau, and to a lesser extent of the lateral compartment. Mean bone-implant contact was extensive and not different between materials (39.5+/-28.1% for OxZr and 42.3+/-31.5% for CoCr) (P=0.873). Considerable cartilage degeneration was induced in the articulating cartilage of the medial tibial plateau 1 year after creating an osteochondral defect in the medial femoral condyle. Treating this defect with a small metal implant, made of either OxZr or CoCr, could not prevent this degeneration. Further optimization of defect-size implants and their placement is required to make this the therapy of choice for the treatment of local cartilage defects.

Articular Cartilage Degeneration Following the Treatment of Focal Cartilage Defects with Ceramic Metal Implants and Compared with Microfracture

Localized cartilage defects are frequently associated with joint pain, reduced function, and a predisposition to the development of osteoarthritis. The purposes of the current study were to investigate the feasibility of the application of defect-sized femoral implants for the treatment of localized cartilage defects and to compare this treatment, in terms of joint degeneration, with the use of microfracture in a goat model of established cartilage defects. In nine Dutch milk goats, a defect in the medial femoral condyle was created in both knees. After ten weeks, the knees were randomly treated by microfracture or by placement of an oxidized zirconium implant. At twenty-six weeks after surgery, the animals were killed. The joints were evaluated macroscopically. Implant osseointegration was measured by automated histomorphometry, and cartilage repair (after microfracture) was scored histologically. Cartilage quality was analyzed macroscopically and histologically. Glycosaminoglycan content and release were measured by alcian blue assay, and the synthesis and release of newly formed glycosaminoglycans were measured by liquid scintillation analysis of the incorporation of 35SO4(2-) in tissue and medium. The mean bone-implant contact (and standard error) was appropriate (14.6%+/-5.4%), and the amount of bone surrounding the implant was extensive (mean, 40.3%+/-4.0%). The healing of the microfracture-treated defects was extensive, although not complete (mean, 18.38+/-0.43 points of a maximum possible score of 24 points). The macroscopic cartilage evaluation did not show any significant differences between the treatments. On histologic evaluation, the cartilage of the medial tibial plateau articulating directly against the treated defects demonstrated significantly more degeneration in the microfracture-treated knees than in the implant-treated knees (p<0.05). This was in accordance with a significantly higher glycosaminoglycan content, higher synthetic activity, and decreased glycosaminoglycan release of the medial tibial plateau cartilage of the implant-treated knees (p<0.05 for all). On histological analysis, degeneration was also found in the cartilage of the lateral tibial plateau and condyle, but no significant difference was found between the treatments. Both microfracture and the use of implants as a treatment for established localized cartilage defects in the medial femoral condyle caused considerable (p < 0.05) degeneration of the directly articulating cartilage as well as in more remote sites in the knee. However, in the medial tibial plateau, the metal implants caused less damage than the microfracture technique.

Articular damage caused by metal plugs in a rabbit model for treatment of localized cartilage defects

Currently, the surgical treatment of localized cartilage defects has limitations. Alternatively, localized cartilage defects may be treated with small biocompatible metal cartilage tacks. Our purpose was to investigate the applicability of defect-size femoral implants. Different bearing materials, cobalt-chromium (CoCr) and oxidized zirconium (OxZr), were tested to evaluate the effect on opposing cartilage quality and osseointegration at different insertion depths. In 18 adult female New Zealand White rabbits, a medial femoral condyle defect was filled with either an OxZr or a CoCr implant (Ø articulating surface 3.5 mm; fixating pin of 9.1 mm length), placed flush, 1mm deep or 1mm protruding with respect to the level of the surrounding cartilage. Animals were sacrificed after 4 weeks. Tibial cartilage quality was scored microscopically and osseointegration measured by automated histomorphometry. Considerable articulating cartilage erosion was found in all conditions. Tibial cartilage quality was least compromised when both implants were placed flush compared to deep (P=0.01) or protruding position (P=0.004) and was better for OxZr compared to CoCr (P=0.011) when left protruding, while no differences were found when placed deep of flush. Most bone formation around the fixating pin was observed in a protruding position (P=0.01). In deep position, more bone-implant contact was observed with CoCr compared to OxZr (P=0.02). OxZr and CoCr implants showed good osseointegration when used as a localized cartilage defect treatment in the rabbit knee; however, opposite cartilage damage was observed in all cases. Placement flush to the surrounding cartilage seems essential and when left protruding OxZr may be less erosive. In conclusion, caution is warranted using small metal implants for the treatment of localized cartilage in the human patient.

P225 Articular damage caused by metal plugs in a rabbit model for treatment of localized cartilage defects

P225 Articular damage caused by metal plugs in a rabbit model for treatment of localized cartilage defects

Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)—5-year follow-up

Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI) is a new operation procedure using a cell seeded collagen matrix for the treatement of localized full-thickness cartilage defects. A prospective clinical investigation was carried out in order to clarify whether this proves suitable and confirms objective and subjective clinical improvement over a period of up to 5 years after operation. Thirty-eight patients with localised cartilage defects were treated with MACT. Within the context of clinical follow-up, these patients were evaluated for up to 5 years after the intervention. Four different scores (Meyers score, Tegner–Lysholm activity score, Lysholm–Gillquist score, ICRS score) as well as the results of six arthroscopies and biopsies obtained from four patients formed the basis of this study. For 15 patients, 5 or more years had elapsed since the operation at the time this study was completed. It was possible to obtain results 5 years postoperatively from 11 (73.3%) of these 15 patients. Overall, we included 25 patients into the evaluation with a 2-year or longer postoperative period. Five years after transplantation 8 out of 11 patients rated the function of their knee as much better or better than before. Three of the four scores showed significant improvement compared to the preoperative value. One score, the Tegner–Lysholm score showed improvement, which, however, did not prove to be significant. The significantly improved results on three scores after 5 years suggest that MACT represents a suitable but cost-intensive alternative in the treatment of local cartilage defects in the knee.