Treatment Of Full-thickness Chondral Defects Research Articles

Particulate cartilage and platelet-rich plasma treatment for knee chondral defects in sheep

PurposeArticular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep.MethodsA full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer’s lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems.ResultsThe PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months.ConclusionsThe results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects.

The Use of Bone Marrow Concentrate in the Treatment of Full-Thickness Chondral Defects

This article is a critical analysis of a study, "Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine Model," by Chu et al. (J Bone Joint Surg Am. 100(2):138-146, 2018). The investigation compared two interventions in the management of full-thickness chondral defects in an equine model: autologous bone marrow concentrate without concomitant microfracture treatment versus microfracture treatment alone. This review analyzes the methodology and results of their investigation and examines how their findings may influence the continued development of therapeutic options for full-thickness cartilage injuries. The study utilized in vitro analysis, arthroscopic assessment, magnetic resonance imaging (MRI) evaluation, and histological analysis to compare the treatments and their influence on the quality of cartilage repair. Although Chu et al. reported similar results between groups, their findings offer insight into the role of arthroscopy, MRI, and histology in the evaluation of repair quality. We compare their findings to those of similar investigations, highlighting the limited therapeutic options and variable clinical outcomes related to the treatment of full-thickness articular cartilage defects.

Carbon Dioxide Insufflation of the Knee in the Treatment of Full-Thickness Chondral Defects With Micronized Human Articular Cartilage

BioCartilage (BC) is dehydrated, minced human hyaline articular cartilage that was developed as an adjunct to microfracture surgery to help stimulate the bone marrow and stem cells to form hyaline-like tissue in full-thickness chondral defects. The minced pieces of BC require a dry environment for application and can easily be disrupted by residual moisture of saline solution in the surrounding tissues. We present a technique of carbon dioxide insufflation during knee arthroscopy as a means of maintaining a dry environment for preparation of the bony bed during BC augmentation of microfracture surgery. This technique is safe and provides more than adequate visualization, as well as a dry environment, to make the arthroscopic application of BC significantly more efficient.

One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45\xa0years

PurposeThe aim of this study is to prospectively evaluate the medium-term effectiveness and regenerative capability of autologous adult mesenchymal stem cells, harvested as bone marrow aspirate concentrate (BMAC), along with a hyaluronan-based scaffold (Hyalofast) in the treatment of ICRS grade 4 chondral lesions of the knee joint, in patients older than 45 years.MethodsA study group of 20 patients with an age >45 years (mean 50.0 ± 4.1 years) was compared to a control group of 20 patients with an age <45 years (mean 36.6 ± 5.0). Patients were prospectively evaluated for 4 years. All patients were evaluated with MRI, KOOS, IKDC, VAS and Tegner scores preoperatively and at two-year and final follow-up.ResultsAt final follow-up, all scores significantly improved (P < 0.001) as follows: all KOOS score categories; Tegner 2 (range 0–4) to 6 (range 4–8) and 3 (range 0–6) to 6 (range 3–10); IKDC subjective (39.2 ± 16.5 to 82.2 ± 8.9) and (40.8 ± 13.9 to 79.4 ± 14.6), in the study and control group respectively. In addition, we show that results are affected by lesion size and number but not from concomitant surgical procedures. MRI showed complete filling in 80 % of patients in the study group and 71 % of patients in the control group. Histological analysis conducted in three patients from the study and two patients from the control group revealed good tissue repair with a variable amount of hyaline-like tissue.ConclusionTreatment of cartilage lesions with BMAC and Hyalofast is a viable and effective option that is mainly affected by lesion size and number and not by age. In particular, it allows to address the >45 years population with functional outcomes that are comparable to younger patients at final follow-up.Level of evidenceProspective cohort study, Level II.

Synovial Fluid Lubricant Properties Are Transiently Deficient After Arthroscopic Articular Cartilage Defect Repair With Platelet-Enriched Fibrin Alone and With Mesenchymal Stem Cells

Background:Following various types of naturally occurring traumatic injury to an articular joint, the lubricating ability of synovial fluid is impaired, with a correlated alteration in the concentration and/or structure of lubricant molecules, hyaluronan, and proteoglycan-4 (PRG4). However, the effect of arthroscopic cartilage repair surgery on synovial fluid lubricant function and composition is unknown.Hypothesis:Arthroscopic treatment of full-thickness chondral defects in horses with (1) platelet-enriched fibrin or (2) platelet-enriched fibrin + mesenchymal stem cells leads to equine synovial fluid with impaired lubricant function and hyaluronan and PRG4 composition.Study Design:Controlled laboratory study.Methods:Equine synovial fluid was aspirated from normal joints at a preinjury state (0 days) and at 10 days and 3 months following fibrin or fibrin + mesenchymal stem cell repair of full-thickness chondral defects. Equine synovial fluid samples were analyzed for friction-lowering boundary lubrication of normal articular cartilage (static and kinetic friction coefficients) and concentrations of hyaluronan and PRG4, as well as molecular weight distribution of hyaluronan. Experimental groups deficient in lubrication function were also tested for the ability of exogenous high–molecular weight hyaluronan to restore lubrication function.Results:Lubrication and biochemical data varied with time after surgery but generally not between repair groups. Relative to preinjury, kinetic friction was higher (+94%) at 10 days but returned to baseline levels at 3 months, while static friction was not altered. Correspondingly, hyaluronan concentration was transiently lower (−64%) and shifted toward lower molecular weight forms, while PRG4 concentration was increased (+210%) in 10-day samples relative to preinjury levels. Regression analysis revealed that kinetic friction decreased with increasing total and high–molecular weight hyaluronan. Addition of high–molecular weight hyaluronan to bring 10-day hyaluronan levels to 2.0 mg/mL restored kinetic friction to preinjury levels.Conclusion:Following arthroscopic surgery for cartilage defect repair, synovial fluid lubrication function is transiently impaired, in association with decreased hyaluronan concentration. This functional deficiency in synovial fluid lubrication can be counteracted in vitro by addition of high–molecular weight hyaluronan.Clinical Relevance:Synovial fluid lubrication is deficient shortly after arthroscopic cartilage repair surgery, and supplementation with high–molecular weight hyaluronan may be beneficial.

Treatment of Full-Thickness Chondral Defects With Hyalograft C in the Knee

Background: Matrix-associated autologous chondrocyte transplantation (MACT) has become an established articular cartilage repair technique. It provides good short-term and midterm results; however, long-term results are lacking. Purpose: To prospectively assess the clinical outcome after MACT in the knee to report long-term results. Study Design: Case series; Level of evidence, 4. Methods: Fifty-three subjects (females/males, 22/31; mean age, 32 ± 12 years) were treated between 2000 and 2006 with a hyaluronan-based MACT product and were followed prospectively. The mean body mass index (BMI) was 24.5 ± 3.8 kg/m2 and the mean defect size was 4.4 ± 1.9 cm2. Fifty patients had single defects and 3 had multiple defects (41 medial femoral condyle, 6 lateral femoral condyle, 2 patella, 1 tibia). Two patients had 2 defects (medial femoral condyle [MFC]/lateral femoral condyle and tibial/MFC), and in 1 case, multiple defects on the MFC were treated. The patients were stratified into 23 “simple,” 22 “complex,” and 8 “salvage” cases. Instability or malalignment was treated before or at the time of graft implantation. For 6 patients with small defects (<2 cm2), microfracturing was used as first-line treatment before MACT. Clinical assessment was performed once a year with the subjective and objective International Knee Documentation Committee (IKDC) scores, Lysholm score, and a modified Cincinnati Knee Rating System. Results: The mean follow-up time was 9.07 ± 2.9 years (range, 5-12 years). Treatment failure occurred in 12 of 53 cases (22.6%) an average of 2.99 ± 1.40 years after surgery. There was 1 failure (4.3%) among the simple cases, 4 failures (18.2%) in complex cases, and 7 failures (87.5%) in salvage cases. Statistically significant increases were observed in all scores at all time points compared with presurgery levels (P < .05). The subjective IKDC score improved from median 40.4 preoperatively to 74.7 at 10-year follow-up (n = 13 patients; P < .05). Conclusion: MACT is an excellent surgical therapy for full-thickness cartilage defects of the knee, with good long-term results for simple defects. However, it should not be used in salvage cases.

Focal femoral condyle resurfacing

Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed.

The adverse effect of elevated body mass index on outcome after autologous chondrocyte implantation

We analysed whether a high body mass index (BMI) had a deleterious effect on outcome following autologous chondrocyte implantation (ACI) or matrix-carried autologous chondrocyte implantation (MACI) for the treatment of full-thickness chondral defects of the knee from a subset of patients enrolled in the ACI vs MACI trial at The Royal National Orthopaedic Hospital. The mean Modified Cincinnati scores (MCS) were significantly higher (p < 0.001) post-operatively in patients who had an ideal body weight (n = 53; 20 to 24.9 kg/m(2)) than in overweight (n = 63; 25 to 30 kg/m(2)) and obese patients (n = 22; > 30 kg/m(2)). At a follow-up of two years, obese patients demonstrated no sustained improvement in the MCS. Patients with an ideal weight experienced significant improvements as early as six months after surgery (p = 0.007). In total, 82% of patients (31 of 38) in the ideal group had a good or excellent result, compared with 49% (22 of 45) of the overweight and 5.5% (one of 18) in the obese group (p < 0.001). There was a significant negative relationship between BMI and the MCS 24 months after surgery (r = -0.4, p = 0.001). This study demonstrates that obese patients have worse knee function before surgery and experience no sustained benefit from ACI or MACI at two years after surgery. There was a correlation between increasing BMI and a lower MCS according to a linear regression analysis. On the basis of our findings patient selection can be more appropriately targeted.

Treatment of Full-Thickness Chondral Defects of the Knee With Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) has been proven an effective method in treating large articular cartilage defects in short- or medium-term follow-up clinical studies. Hypothesis: First generation ACI of patients with large full-thickness chondral defects of the knee could yield reliable functional outcomes after a minimum follow-up of 5 years. Study Design: Case series; Level of evidence, 4. Methods: Between 1997 and 2005, 42 patients (45 knees) underwent first generation ACI for symptomatic chondral defects of the knee. All patients had moderate to large (mean, 5.33 cm2) full-thickness chondral defects. Patients were evaluated using the International Cartilage Repair Society (ICRS) score, the International Knee Documentation Committee (IKDC) Knee Examination Form, the Tegner activity score, the Lysholm score, the Stanmore functional rating score, and a visual analog scale (VAS) for pain. Results: The mean follow-up was 96 months (range, 62-144 months). At the final follow-up, a significant increase in all scores was recorded. Compared with preoperative findings, the median Lysholm score significantly improved, increasing from 56.0 to 89.0 (P < .05). The IKDC and the Tegner activity score showed significant improvement postoperatively, increasing from 45 and 5.5 to 69 and 6.5, respectively (P < .05). The mean ICRS improved from grade 3.8 preoperatively to grade 2.8 postoperatively (P < .05). The Stanmore functional rating score and the VAS pain score were decreased from 3.06 and 7.33 to 0.94 and 2, respectively (P < .05). Reoperation was required in 5 patients. In 2 of them graft failure was recorded due to degeneration or partial detachment, respectively. Conclusion: The long-term outcomes of our series support the effectiveness of first generation ACI in both pain relief and functional rehabilitation of patients with large full-thickness osteochondral defects of the knee.

Treatment of Full-Thickness Chondral Defects with Hyalograft C in the Knee

Background Tissue engineering has become available for cartilage repair in clinical practice. Hypothesis The treatment of full-thickness chondral defects in the knee with a hyaluronan-based scaffold seeded with autolo-gous chondrocytes provides stable improvement of clinical outcome up to 7 years. Study Design Case series; Level of evidence, 4. Methods Fifty-three patients with deep osteochondral defects in the knee were treated with Hyalograft C. The mean age at implantation was 32 6 12 years, the mean defect size was 4.4 6 1.9 cm2, and the mean body mass index was 24.5 6 3.8 kg/m2. Implantations were performed with miniarthrotomy or arthroscopy. The primary indications for implantation with Hyalograft C included young patients with a stable joint, normal knee alignment, and isolated chondral defects with otherwise healthy adjacent cartilage. The secondary indications were patients who did not meet the primary indication criteria or were salvage procedures. Forty-two patients with primary indications and 11 patients with secondary indications were evaluated. Outcome was evaluated with the International Cartilage Repair Society and International Knee Documentation Committee scales, the Lysholm score, the modified Cincinnati score, and with Kaplan-Meier survival analysis. Statistical analysis consisted of bivariate correlation analysis and unpaired, 2-tailed t tests. Results A highly significant increase (P<001) in all knee scores was found in patients treated for the primary indications. Nine of 11 secondary indication cases underwent total knee arthroplasty due to persisting pain between 2 and 5 years after implantation. Graft failure occurred in 3 of 42 patients with primary indication between 6 months and 5 years after implantation. Kaplan-Meier survival demonstrated significantly different chances for survival between primary and secondary outcome and between simple, complex, and salvage cases, respectively (P <.001). Conclusion Hyalograft C autograft provides clinical improvement in healthy young patients with single cartilage defects. Less complicated surgery and lower morbidity are considered advantages of the technique. The results of treatment with Hyalograft C as a salvage procedure or in patients with osteoarthritis are poor.

Arthroscopic drilling vs. micro-invasive surgery for the treatment of full-thickness chondral defects

This retrospective study was to compare the clinical effects of arthroscopie drilling with arthroscopic microfracture technology on full-thickness chondral defects in 68 patients treated between March 2003 and June 2005. The patients were followed up for an average of (20 ± 5 ) months. Lysholm score and Tegner scale were used to evaluate the efficacy. For the arthrescopic drilling group (n = 15 ) and the microfracture surgery group (n =27) , total effective rates were 12/15 and 85% (23/27), respectively. Our data suggest that those two methods provide simple and effective surgical procedure for the treatment of chondral defects of the knee; the results of arthroscopic microfracture were significantly better than arthroscopic drilling. Key words: Knee joint; Arthroscopy

Microfracture for Osteochondritis Dissecans Lesions

Microfracture is a marrow stimulating technique used in the treatment of full-thickness chondral defects. In the case of osteochondritis dissecans lesions, which are unstable and require extraction, microfracture is a viable treatment option. It is a relatively simple procedure that can be done in conjunction with other arthroscopic procedures and require minimal equipment. Careful surgical technique, including removal of the calcified cartilage layer as well as adherence to a stringent postoperative regimen, is critical to the long-term success of this procedure.

Osteochondral allograft transplantation in the knee

Despite significant improvements for the past 20 years in the treatment of full-thickness chondral defects with the use of chondroprotective biological methods (microfracture, autologous chondrocyte transplantation, osteochondral autograft, and periosteal graft), the treatment of large osteochondral defects in young and physically active population is still challenging. Alternatives for the treatment of chondral defects exceeding 3 cm in size are limited, and among them, allografts have been used longer than any other treatment methods with the most favorable results. The success rates for osteochondral allograft transplantation have been reported as 95%, 71%, and 66% at 5, 10, and 20 years, respectively. Factors that adversely affect long-term results include advanced age, allograft transplantation to both sides of the joint, inappropriate loading, osteoarthritis, and osteonecrosis due to steroid use. Today, as a result of improvements in tissue-organ transplantation, increased availability of fresh tissue from donors, and increased demand from patients and physicians, there has been growing interest in the use of osteochondral allografts in selected patients to delay arthroplasty for chondral defects.

Treatment of Full-Thickness Chondral Defects in the Knee With Autologous Chondrocyte Implantation

Autologous chondrocyte implantation (ACI) has now been performed for over a decade in the United States. ACI has been demonstrated as a reproducible treatment option for large, full-thickness, symptomatic chondral injuries of the knee. As clinical experience has expanded and indications broadened to more complex cartilage defects, it has become evident that aggressive treatment of coexisting knee pathology is essential for optimal results. This includes management of malalignment, ligamentous, and/or meniscal deficiency, and subchondral bone loss to make the intra-articular environment as ideal as possible for successful cartilage restoration. Additionally, refinements in the rehabilitation necessary for biologic cartilage repair have been made, based on better understanding of the maturation process of the repair cartilage, allowing for earlier initiation of knee range of motion, strengthening exercises, and weight bearing. These changes have enhanced the recovery for the patient and decreased the risk of motion deficits. This article will discuss patient selection for ACI, review ACI surgical technique, including management of coexisting knee pathology, present postoperative ACI rehabilitation guidelines, and summarize clinical outcomes after ACI.

Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair

Traumatic articular cartilage injuries heal poorly and may predispose patients to the early onset of osteoarthritis. One current treatment relies on surgical delivery of autologous chondrocytes that are prepared, prior to implantation, through ex vivo cell expansion of cartilage biopsy cells. The requirement for cell expansion, however, is both complex and expensive and has proven to be a major hurdle in achieving a widespread adoption of the treatment. This study presents evidence that autologous chondrocyte implantation can be delivered without requiring ex vivo cell expansion. The proposed improvement relies on mechanical fragmentation of cartilage tissue sufficient to mobilize embedded chondrocytes via increased tissue surface area. Our outgrowth study, which was used to demonstrate chondrocyte migration and growth, indicated that fragmented cartilage tissue is a rich source for chondrocyte redistribution. The chondrocytes outgrown into 3-D scaffolds also formed cartilage-like tissue when implanted in SCID mice. Direct treatment of full-thickness chondral defects in goats using cartilage fragments on a resorbable scaffold produced hyaline-like repair tissue at 6 months. Thus, delivery of chondrocytes in the form of cartilage tissue fragments in conjunction with appropriate polymeric scaffolds provides a novel intraoperative approach for cell-based cartilage repair.

Autologous Chondrocyte Implantation versus Debridement for Treatment of Full-Thickness Chondral Defects of the Knee

Background Studies that compare the effectiveness of different cartilage repair treatments are needed to update treatment algorithms. Hypothesis Autologous chondrocyte implantation provides greater improvement in overall condition score than does debridement at a minimum of 3 years’ follow-up. Study Design Cohort study; Level of evidence, 3. Methods Cohorts for debridement and autologous chondrocyte implantation each included 58 Cartilage Repair Registry patients who met study criteria. A retrospective analysis was performed on prospectively collected baseline and follow-up data. Results Patients in the autologous chondrocyte implantation and debridement groups had similar demographics and chondral lesions at baseline. However, more autologous chondrocyte implantation patients failed a previous debridement or marrow stimulation procedure than did debridement patients. Follow-up outcome assessments were completed by 54 autologous chondrocyte implantation patients and 42 debridement patients. Eighty-one percent of the autologous chondrocyte implantation patients and 60% of the debridement patients reported median improvements of 5 points and 2 points, respectively, in the overall condition score. Autologous chondrocyte implantation patients also reported greater improvements in the median pain and swelling scores than did debridement patients. The treatment failure rate was the same for both autologous chondrocyte implantation and debridement patients. Eighteen autologous chondrocyte implantation patients and 1 debridement patient had at least 1 subsequent operation. Conclusion Although patients treated with debridement for symptomatic, large, focal, chondral defects of the distal femur had some functional improvement at follow-up, patients who received autologous chondrocyte implantations obtained higher levels of knee function and had greater relief from pain and swelling at 3 years.

Paper #125 Marrow stimulation techniques versus autologous chondrocyte implantation for treatment of full-thickness chondral defects of the knee: comparison of patient outcomes at 3-5 years

Autologous cultured chondrocyte implantation (ACI), for articular cartilage lesions of the distal femur, generally demonstrates effectiveness in 80-85% of cases. However, no studies have compared these results to those of marrow stimulation techniques (MST): abrasion, drilling, or microfracture. The purpose of this multicenter, prospective study was to compare patient reported outcomes at a minimum of three years between patients treated with autologous chondrocyte implantation and marrow stimulation techniques.