Second-generation Autologous Chondrocyte Implantation Research Articles

Etiology of Cartilage Lesions Does Not Affect Clinical Outcomes of Patellofemoral Autologous Chondrocyte Implantation.

To determine the relationship between cartilage lesion etiology and clinical outcomes after second-generation autologous chondrocyte implantation (ACI) in the patellofemoral joint (PFJ) with a minimum of 2 years' follow-up. A retrospective review of all patients that underwent ACI in the PFJ by a single surgeon was performed. Seventy-two patients with a mean follow-up of 4.2 ± 2.0 years were enrolled in this study and were stratified into 3 groups based on the etiology of PFJ cartilage lesions: patellar dislocation (group 1; n = 23); nontraumatic lesions, including chondromalacia, osteochondritis dissecans, and degenerative defects (group 2; n = 28); and other posttraumatic lesions besides patellar dislocations (group 3; n = 21). Patient's mean age was 29.6 ± 8.7 years. Patients in group 1 were significantly younger (25.4 ± 7.9 years) than group 2 (31.7 ± 9.6 years; P = 0.025) and group 3 (31.5 ± 6.6 years; P = 0.05). Body mass index averaged 26.2 ± 4.3 kg/m2, with a significant difference between group 1 (24.4 ± 3.2 kg/m2) and group 3 (28.7 ± 4.5 kg/m2; P = 0.005). A clinical comparison was established between groups based on patient-reported outcome measures (PROMs) and failure rates. Neither pre- nor postoperative PROMs differed between groups (P > 0.05). No difference was seen in survivorship between groups (95.7% vs. 82.2% vs. 90.5%, P > 0.05). Cartilage lesion etiology did not influence clinical outcome in this retrospective study after second generation ACI in the PFJ. Level III, retrospective comparative study.

Prior Surgery Negatively Affects Cell Culture Identity in Patients Undergoing Autologous Chondrocyte Implantation

Background: Recently, a cell identity assay has been introduced to evaluate the identity of cultured chondrocytes before autologous chondrocyte implantation (ACI), which was shown to be associated with graft survival after ACI. Purpose: To identify the influence of several patient- and lesion-specific factors on cell identity and viability assays. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 187 patients with second-generation ACI were included in this study. Patient and lesion characteristics, cell viability, cell identity, and biopsy specimen weight were recorded for each patient. A binomial logistic regression model was utilized to determine patient-specific predictive factors for cell product quality. Results: The implanted ACI cell products showed a cell viability of 93% ± 2.4% (mean ± SD; range, 84-98) with an identity score of 5.8 ± 2.1 (range, –0.08 to 9.46). Patients with multiple previous surgical procedures on the index knee had significantly lower cell identity scores when compared with patients without previous surgery (odds ratio = 0.31; 95% CI, 0.16-0.59; P < .001). Patients without surgical history had significantly higher cell identity scores than patients with 1 and ≥2 previous surgical procedures on the index knee (6.32 vs 5.32 vs 5.05; P = .006 and P < .001, respectively). Cell viability was not predicted by any preoperative variable (P > .05). Cell identity and viability were not associated with each other or with biopsy specimen weight (P > .05). Conclusion: Cartilage biopsy specimens from patients with ≥1 previous surgical procedures resulted in implants with lower cell identity scores when compared with patients without previous operations. None of the other patient- or lesion-specific factors were correlated, specifically biopsy specimen weight.

Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans.

SummaryHuman mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSCHS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency.

Severe Bone Marrow Edema Among Patients Who Underwent Prior Marrow Stimulation Technique Is a Significant Predictor of Graft Failure After Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure; however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MSTs). Purpose: To identify which factors may predict decreased graft survival after ACI among patients who underwent a prior MST. A secondary aim was to investigate the specificity of these predictors. Study Design: Case-control study; Level of evidence, 3. Methods: In this review of prospectively collected data, the authors analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen-covered ACI (case group). The case group was divided into graft failure ACI (n = 8, 21%) and successful ACI (n = 30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft: age, body mass index, sex, defect characteristics (number, size, location, etiology, type), presence of kissing lesion, intraoperative presence of intralesional osteophyte, time between an MST and ACI, previous surgery, duration of the symptoms, and concomitant surgical procedure. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME), graded I (absent) to IV (severe), and the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group without a prior MST was matched to investigate the specificity of the previously determined predictors. These patients were matched individually according to age, sex, body mass index, and outcome of the procedure (failure [n = 8] or successful [n = 30] per the case group). Results: In the case group, the presence of preoperative severe BME was significantly higher among patients with failed ACI as compared with patients with successful ACI (P < .001). In the control group, the presence of severe BME was not significantly different between the failure and successful groups (P = .747). The ACI graft failure rate among patients with a prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively, resulting in a significantly lower survival rate as compared with patients with a prior MST and without severe BME (5-year graft failure rate, 6.5%; P < .001). All the other parameters did not differ significantly. Conclusion: After a prior MST, the presence of grade IV BME by MRI was a predictive factor for graft failure among patients who then underwent second-generation ACI.

A large knee osteochondral lesion treated using a combination of osteochondral autograft transfer and second-generation autologous chondrocyte implantation: A case report.

BackgroundFull-thickness knee cartilage defects greater than 4 cm2 are best treated with autologous chondrocyte implantation (ACI). Since the articular cartilage surrounding the site of implantation does not always have the normal thickness desirable for successful engraftment, there may be benefit in combining ACI with osteochondral autograft transfer, which provides immediate restoration of condylar contour and mechanical function.Case presentationA 19 year-old male who sustained a traumatic anterolateral femoral condyle osteochondral fracture underwent arthroscopic knee surgery three months after injury to harvest healthy cartilage to be sent to the Japan Tissue Engineering Co., Ltd. (J-TEC) for cartilage culture. The patient was re-admitted after four weeks to undergo a procedure using the Osteochondral Autograft Transfer System (OATS®) and the J-TEC autologous cultured cartilage (JACC®) system. Three 4.75-mm osteochondral cylindrical cores were harvested from non-weight-bearing areas of the knee and were transplanted to the lateral periphery of the lateral femoral condyle defect. The cultured cartilage was implanted to the remaining defect with a periosteal cover harvested from the anterolateral ridge of the lateral femoral condyle. Continuous passive range of motion exercises and gait retraining were immediately initiated, with strict no weight-bearing precaution on the operated limb. Partial weight-bearing was allowed four weeks after surgery, which was progressed to full weight-bearing after another two weeks.ConclusionACI must be viewed as a complementary procedure to osteochondral transplantation and this hybrid technique appears to be a promising surgical approach and treatment option for large cartilage lesions, especially in the younger population.

Autologous Chondrocyte Implantation and Tibial Tubercle Osteotomy for Patellofemoral Chondral Defects: Improved Pain Relief and Occupational Outcomes Among US Army Servicemembers

Background: The occupational and functional results of patellofemoral autologous chondrocyte implantation (ACI) are underreported. This investigation sought to establish clinical outcomes and rates for return to work in a predominantly high-demand military cohort undergoing this procedure. Purpose: To determine the return-to-work, pain relief, and perioperative complication rates in a high-demand athletic cohort undergoing patellofemoral ACI. Study Design: Case series; Level of evidence, 4. Methods: All military servicemembers from 2 military medical centers undergoing ACI for high-grade patellofemoral chondral defects between 2006 and 2014 were identified, and data were abstracted from their medical records and clinical databases. Demographic and surgical variables were obtained for patients with at least 2 years of postoperative follow-up, and perioperative complications, rates of return to work, and survivorship from revision were quantified. Results: Seventy-two patients (72%) had >2-year follow-up and had patellofemoral ACI for high-grade chondral defects, with 66 knees (91%) undergoing a concomitant offloading tibial tubercle osteotomy. Mean follow-up was 4.3 years (range, 2.0-9.9 years). The mean ± SD age was 34.4 ± 6.1 years; 86% were male; and 57% were involved in military occupational specialties of heavy or very heavy demand. Second-generation patellofemoral ACI with a type I/III collagen membrane was used for 85% of knees. Most defects were isolated to the patella (n = 40, 55%). The mean total defect surface area was 4.5 ± 2.9 cm2 (range, 2.7-13.5 cm2). Fifty-six servicemembers (78%) returned to their occupational specialties. Three patients (4.1%) were classified as having surgical failures, requiring subsequent knee arthroplasty (n = 2) or a revision chondral procedure (n = 1). Mean visual analog scores improved significantly from 6.5 ± 1.5 to 3.2 ± 2.1 (P < .0001). Multivariate analysis identified use of a periosteal patch as the only significant independent predictor for surgical (P = .013) and overall (P = .033) failures. Age <30 years (P = .019), female sex (P = .019), and regular tobacco use (P = .011) were independent predictors of overall failure. Conclusion: For patellofemoral chondral defects without a failed primary procedure, second-generation ACI successfully returned to work 78% of patients of moderate to very heavy occupational demand with significantly decreased patient-reported knee pain. Risk factors after ACI for patellofemoral articular lesions for overall failure were age <30 years, female sex, and tobacco use, while surgical and overall failures were associated with periosteal patch use.

Autologous Chondrocyte Implantation (ACI) for Knee Cartilage Defects: A Review of Indications, Technique, and Outcomes.

* Autologous chondrocyte implantation (ACI) was first developed in the late 1980s for the treatment of articular cartilage defects in the knee. The first generation of ACI utilized a periosteal patch to contain the cultured chondrocyte solution within the defect. Because of issues with periosteal graft hypertrophy, ACI with use of a collagen membrane patch (second-generation ACI) was developed. Finally, the application of chondrocytes within a matrix (third-generation ACI) was created to improve cell delivery, to allow for minimally invasive implantation, to better replicate normal cartilage architecture, and to accelerate patient rehabilitation. As of December 2016, only 1 third-generation ACI product (matrix-induced autologous chondrocyte implantation, or MACI) has been cleared for marketing by the U.S. Food and Drug Administration (FDA) and is available in the United States.* ACI (regardless of generation) is effective for the treatment of high-grade tibiofemoral cartilage defects. However, issues with coronal alignment, ligament laxity/instability, and meniscal deficiency must be addressed or the outcomes following ACI will be poor.* Because of the extended time that is required for graft maturation, special consideration must be given to return-to-play protocols as athletes can regain strength and neuromuscular coordination well before the graft has sufficiently matured.

Autologous Bone Plug Supplemented With Autologous Chondrocyte Implantation in Osteochondral Defects of the Knee

Background: Structural and functional outcome of bone graft with first- or second-generation autologous chondrocyte implantation (ACI) in treating cartilage and subchondral bone defect has not been reported previously. Purpose: To evaluate the outcome of simultaneous transplantation of an autologous bone plug with first- or second-generation ACI for restoration of concomitant subchondral bone and full-thickness cartilage defect in the femoral condyle of the knee. Study Design: Case series; Level of evidence, 4. Methods: Seventeen patients (mean ± SD age, 27 ± 7 years; range, 17-40 years)—12 with osteochondritis dissecans (International Cartilage Repair Society [ICRS] grades 3 and 4) and 5 with an isolated osteochondral defect (ICRS grade 4)—had the defect reconstructed with implantation of a unicortical autologous bone graft combined with ACI (the OsPlug technique). Functional outcome was assessed with Lysholm scores obtained preoperatively and at 1 and 5 years postoperatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score (magnetic resonance observation of cartilage repair tissue), and ICRS II histology score. Formation of a subchondral lamina and lateral integration of the bone grafts were evaluated from magnetic resonance imaging scans. Results: The mean defect size was 4.5 ± 2.6 cm2 (range, 1-9 cm2), and the mean depth was 11.3 ± 5 mm (range, 5-18 mm). The preoperative Lysholm score improved from 45 (interquartile range [IQR], 24; range, 16-79) to 77 (IQR, 28; range, 41-100) at 1 year (P = .001) and 70 (IQR, 35; range, 33-91) at 5 years (P = .009). The mean OAS of the repair site was 6.2 (range, 0-9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22 (range, 20-85) at 2.6 ± 1.8 years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft, as assessed on magnetic resonance imaging scan, and a low OAS were significantly associated with a poor Lysholm score and failure. A total of 3 patients had treatment failure, with 1 requiring total knee replacement at 5 years (Lysholm score of 33 at failure) and the other 2 requiring further surgical intervention because of persistent symptoms at 2 and 4 years, respectively (both had Lysholm score of 45 at failure). The Lysholm score in these patients before failure were still noted to be higher than at the preoperative level. Conclusion: The OsPlug technique shows significant improvement of functional outcome for up to 5 years in patients with high-grade osteochondritis dissecans or osteochondral defect. This is the first report describing association of bone graft integration with functional outcome after such a procedure. It also demonstrates histologic evidence of integration of the repair cartilage with the underlying bone graft.

Comparison of Collagen Graft Fixation Methods in the Porcine Knee: Implications for Matrix-Assisted Chondrocyte Implantation and Second-Generation Autologous Chondrocyte Implantation

To evaluate the fixation integrity at time zero of a type I/III collagen patch secured to a chondral defect in the porcine knee using methods typically employed in autologous chondrocyte implantation (ACI) and matrix-assisted chondrocyte implantation. Twenty-four porcine knee specimens underwent a medial parapatellar arthrotomy. A prefabricated template was used to create cartilage defects of 2 cm(2) in the medial femoral condyle. A size-matched collagen patch was fashioned. Four methods of fixation to the chondral defect were analyzed: group 1-saline, group 2-fibrin glue around the periphery of the patch, group 3-fibrin glue applied to the base of the defect and around the periphery of the patch, group 4-6-0 vicryl suture and fibrin glue around the periphery of the patch. Collagen patch fixation was assessed at intervals of 60, 300, 600, 900, and 1,200 cycles from full extension to 90° of flexion, performed manually without application of axial force. Patch fixation was evaluated by 2 independent observers using a customized scoring scale. Mean peripheral detachment of the patch and chondral defect uncovering remained less than 25% for all groups. Area of defect uncovering was significantly increased in group 2 compared with group 4 after 900 and 1,200 cycles (P= .0014 and P= .0025, respectively). Fibrin glue applied to the base of the defect, or suturing of the patch, reduced deformation significantly after 900 cycles. Suture increases the stability of fixation of a type I/III collagen patch to a chondral defect better than fibrin glue alone in the porcine knee after repetitive cycling, with respect to patch detachment and chondral defect uncovering. Application of fibrin glue to the base of the defect, or securing the patch with suture, decreases collagen patch deformation. In cases where minimally invasive techniques do not allow suture fixation of the collagen patch, scaffold fixation may be compromised during articular motion protocols typically used after second- and third-generation ACI procedures.

Articular Cartilage Treatment in High-Level Male Soccer Players: A Prospective Comparative Study of Arthroscopic Second-Generation Autologous Chondrocyte Implantation Versus Microfracture

Articular Cartilage Treatment in High-Level Male Soccer Players: A Prospective Comparative Study of Arthroscopic Second-Generation Autologous Chondrocyte Implantation Versus Microfracture

Articular Cartilage Treatment in High-Level Male Soccer Players

Background: Soccer is a highly demanding sport for the knee joint, and chondral injuries can cause disabling symptoms that may jeopardize an athlete’s career. Articular cartilage lesions are difficult to treat, and the increased mechanical stress produced by this sport makes their management even more complex. Hypothesis: To evaluate whether the regenerative cell-based approach allows these highly demanding athletes a better functional recovery compared with the bone marrow stimulation approach. Study Design: Cohort study; Level of evidence, 2. Methods: Forty-one professional or semiprofessional male soccer players were treated from 2000 to 2006 and evaluated prospectively at 2 years and at a final 7.5-year mean follow-up (minimum, 4 years). Twenty-one patients were treated with arthroscopic second-generation autologous chondrocyte implantation (Hyalograft C) and 20 with the microfracture technique. The clinical outcome of all patients was analyzed using the cartilage standard International Cartilage Repair Society (ICRS) evaluation package. The sport activity level was evaluated with the Tegner score, and the recovery time was also recorded. Results: A significant improvement in all clinical scores from preoperative to final follow-up was found in both groups. The percentage of patients who returned to competition was similar: 80% in the microfracture group and 86% in the Hyalograft C group. Patients treated with microfracture needed a median of 8 months before playing their first official soccer game, whereas the Hyalograft C group required a median time of 12.5 months (P = .009). The International Knee Documentation Committee (IKDC) subjective score showed similar results at 2 years’ follow-up but significantly better results in the Hyalograft C group at the final evaluation (P = .005). In fact, in the microfracture group, results decreased over time (from 86.8 ± 9.7 to 79.0 ± 11.6, P < .0005), whereas the Hyalograft C group presented a more durable outcome with stable results (90.5 ± 12.8 at 2 years and 91.0 ± 13.9 at the final follow-up). Conclusion: Despite similar success in returning to competitive sport, microfracture allows a faster recovery but present a clinical deterioration over time, whereas arthroscopic second-generation autologous chondrocyte implantation delays the return of high-level male soccer players to competition but can offer more durable clinical results.

Arthroscopic Second-Generation Autologous Chondrocyte Implantation

Background: Regenerative techniques, such as autologous chondrocyte implantation (ACI), have emerged as a potential therapeutic option for the treatment of chondral lesions, aiming to recreate a hyaline-like tissue in the damaged articular surface. The clinical application of the regenerative approach is well documented for different types of scaffold but mostly with an evaluation of the clinical outcome at short-term follow-up. Purpose: This study was conducted to analyze the clinical outcome obtained with arthroscopic second-generation ACI up to 7 years’ follow-up, to assess the durability of the results, and understand its real potential over time. Study Design: Case series; Level of evidence, 4. Methods: Sixty-two consecutive patients, 48 men and 14 women with a mean age of 28.1 ± 11.4 years, affected by chondral lesions of the femoral condyles were enrolled and treated with arthroscopic implantation of the bioengineered tissue Hyalograft C. The average size of the defects was 2.5 ± 1.0 cm2. Patients were evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores every year for 7 years, and a magnetic resonance imaging evaluation was performed. Results: A statistically significant improvement was observed in all scores from the basal evaluation to the 84 months’ follow-up. The IKDC subjective score increased from 39.6 ± 15.0 to 73.6 ± 18.8 at 12 months; a further slight improvement was observed at 24 months’ follow-up (76.5 ± 20.7), and then the results were stable and reached a final 7-year value of 77.3 ± 21.5. Seven cases (11%) failed. A better outcome was obtained in young active men, whereas the worst results were found in degenerative lesions or when previous surgery had been performed. Postoperative magnetic resonance imaging studies in 42 cases revealed a complete filling of the cartilage defect in 57% of the lesions, complete integration of the graft in 62% of cases, intact repair tissue surface in 50%, homogeneous repair tissue structure in 43%, and a graft signal-intensity score that was isointense with the adjacent native cartilage in 43% and 48% of the cases in dual T2–fast spin echo and 3-dimensional gradient echo with fat suppression sequences, respectively. Conclusion: The analysis of this group of homogeneous patients, prospectively evaluated every year for 7 years, shows that this bioengineered approach with the proper indications may offer good and stable clinical results over time.

Second-Generation Autologous Chondrocyte Implantation

Background Aging is responsible for degenerative changes in all cartilage elements, thus impairing its properties and healing potential. Most studies on surgical procedures for cartilage focus on young patients because these procedures are generally not considered suitable for older patients. Purpose To analyze the clinical outcome of cartilage lesion treatment using second-generation autologous chondrocyte implantation (ACI) techniques in patients more than 40 years old with no clear signs of osteoarthritis, to understand their real potential in relation to aging, the failure rate, and complications in older patients. Study Design Case series; Level of evidence, 4. Methods Sixty-one patients with grade III to IV cartilaginous lesions of the condyles with no clear signs of osteoarthritis and a minimum age of 40 years were treated with second-generation ACI and prospectively evaluated at 5 years’ follow-up. Twenty-two patients were treated with arthroscopic Hyalograft C implantation, and 39 underwent the open Chondro-Gide MACI procedure. Results A significant improvement in both subjective and objective evaluations was observed. The International Knee Documentation Committee (IKDC) subjective score improved from 36.8 ± 8.4 to 68.1 ± 21.8 at the final evaluation. The failure rate was 20%. A faster improvement was observed in the group treated with the arthroscopic Hyalograft C technique, whereas similar scores were found at the 24-month follow-up and final evaluation. Conclusion A clinical improvement was found in patients more than 40 years old, who in most cases benefited from second-generation ACI with good results lasting at medium-term follow-up. However, the results were inferior with respect to those previously found for younger populations, and the failure rate at medium-term follow-up was also higher. These findings were consistent in the 2 treatment groups. The only difference was the faster recovery when the arthroscopic approach was used.

Autologous Chondrocyte Implantation

The purpose of the present study was to determine (1) whether the current literature supports the choice of using autologous chondrocyte implantation over other cartilage procedures with regard to clinical outcome, magnetic resonance imaging, arthroscopic assessment, and durability of treatment, (2) whether the current literature supports the use of a specific generation of autologous chondrocyte implantation, and (3) whether there are patient-specific and defect-specific factors that influence outcomes after autologous chondrocyte implantation in comparison with other cartilage repair or restoration procedures. We conducted a systematic review of multiple databases in which we evaluated Level-I and II studies comparing autologous chondrocyte implantation with another cartilage repair or restoration technique as well as comparative intergenerational studies of autologous chondrocyte implantation. The methodological quality of studies was evaluated with use of Delphi list and modified Coleman methodology scores. Effect size analysis was performed for all outcome measures. Thirteen studies (917 subjects) were included. Study methodological quality improved with later publication dates. The mean modified Coleman methodology score was 54 (of 100). Patients underwent autologous chondrocyte implantation (n = 604), microfracture (n = 271), or osteochondral autograft (n = 42). All surgical techniques demonstrated improvement in comparison with the preoperative status. Three of seven studies showed better clinical outcomes after autologous chondrocyte implantation in comparison with microfracture after one to three years of follow-up, whereas one study showed better outcomes two years after microfracture and three other studies showed no difference in these treatments after one to five years. Clinical outcomes after microfracture deteriorated after eighteen to twenty-four months (in three of seven studies). Autologous chondrocyte implantation and osteochondral autograft demonstrated equivalent short-term clinical outcomes, although there was more rapid improvement after osteochondral autograft (two studies). Although outcomes were equivalent between first and second-generation autologous chondrocyte implantation and between open and arthroscopic autologous chondrocyte implantation, complication rates were higher with open, periosteal-cover, first-generation autologous chondrocyte implantation (four studies). Younger patients with a shorter preoperative duration of symptoms and fewer prior surgical procedures had the best outcomes after both autologous chondrocyte implantation and microfracture. A defect size of >4 cm(2) was the only factor predictive of better outcomes when autologous chondrocyte implantation was compared with a non-autologous chondrocyte implantation surgical technique. Cartilage repair or restoration in the knee provides short-term success with microfracture, autologous chondrocyte implantation, or osteochondral autograft. There are patient-specific and defect-specific factors that influence clinical outcomes.

Patellofemoral Full-Thickness Chondral Defects Treated With Second-Generation Autologous Chondrocyte Implantation

Background Patellofemoral lesions represent a very troublesome condition to treat for orthopaedic surgeons; however, second-generation autologous chondrocyte implantation (ACI) seems to offer an interesting treatment option with satisfactory results at short-term follow-up. Hypothesis Hyaluronan-based scaffold seeded with autologous chondrocytes is a viable treatment for the damaged articular surface of the patellofemoral joint. Study Design Case series; Level of evidence, 4. Methods Among a group of 38 patients treated for full-thickness patellofemoral chondral lesions with second-generation ACI, we investigated 34 who were available for final follow-up at 5 years. These 34 had chondral lesions with a mean size of 4.45 cm2. Twenty-one lesions were located on the patella, 9 on the trochlea, and 4 patients had multiple lesions: 3 had patellar and trochlear lesions, and 1 had patellar and lateral femoral condyle lesions. Twenty-six lesions (76.47%) were classified as International Cartilage Repair Society (ICRS) grade IV A or B, 5 lesions (14.70%) were grade IIIC, and 3 (8.82%) were lesions secondary to osteochondritis dissecans (OCD). Results were evaluated using the International Knee Documentation Committee (IKDC) 2000 subjective and objective scores, EuroQol (EQ) visual analog scale (VAS), and Tegner scores at 2 and 5 years. Eight patients had second-look arthroscopy and biopsies. Results All the scores used demonstrated a statistically significant improvement (P < .0005) at 2 and 5 years’ follow-up. Objective preoperative data improved from 8 of 34 (23.52%) normal or nearly normal knees to 32 of 34 (94.12%) at 2 years and 31 of 34 (91.17%) at 5 years after transplantation. Mean subjective scores improved from 46.09 points preoperatively to 77.06 points 2 years after implantation and 70.39 at 5 years. The Tegner score improved from 2.56 to 4.94 and 4.68, and the EQ VAS improved from 56.76 to 81.47 and 78.23 at 2 and 5 years’ follow-up, respectively. A significant decline of IKDC subjective and Tegner scores was found in patients with multiple and patellar lesions from 2 to 5 years’ follow-up. Second-look arthroscopies in 8 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance. Conclusion Hyaluronan-based scaffold seeded with autologous chondrocytes can be a viable treatment for patellofemoral chondral lesions.

Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results

IntroductionSecond-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed®-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee.MethodsClinical outcome after 4-year clinical follow-up was assessed in 19 patients with preoperatively radiologically confirmed osteoarthritis and a Kellgren-Lawrence score of 2 or more. Clinical scoring was performed before implantation of the graft and 6, 12, and 48 months after implantation using the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) score, and the International Cartilage Repair Society (ICRS) score. Cartilage regeneration and articular resurfacing were assessed by magnetic resonance imaging (MRI) 4 years after implantation of the autologous cartilage graft.ResultsSignificant improvement (P < 0.05) of the Lysholm and ICRS scores was observed as early as 6 months after implantation of BioSeed®-C and remained stable during follow-up. The IKDC score showed significant improvement compared with the preoperative situation at 12 and 48 months (P < 0.05). The KOOS showed significant improvement in the subclasses pain, activities of daily living, and knee-related quality of life 6 months as well as 1 and 4 years after implantation of BioSeed®-C in osteoarthritic defects (P < 0.05). MRI analysis showed moderate to complete defect filling with a normal to incidentally hyperintense signal in 16 out of 19 patients treated with BioSeed®-C. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years.ConclusionsThe results show that the good clinical outcome achieved 1 year after implantation of BioSeed®-C remains stable over the course of a period of 4 years and suggest that implanting BioSeed®-C is a promising treatment option for the repair of focal degenerative defects of the knee.

Arthroscopic Second-Generation Autologous Chondrocyte Implantation Compared with Microfracture for Chondral Lesions of the Knee

Background Various approaches have been proposed to treat articular cartilage lesions, which are plagued by inherent limited healing potential. Purpose To compare the clinical outcome of patients treated with second-generation autologous chondrocyte implantation implants with those treated with the microfracture repair technique at 5-year follow-up. Study Design Cohort study; Level of evidence, 2. Methods Eighty active patients (mean age, 29.8 years) and grade III to IV cartilage lesions of the femoral condyles or trochlea were treated with arthroscopic second-generation autologous chondrocyte implantation Hyalograft C or microfracture (40 patients per group). Patients achieved a minimum 5-year follow-up and were prospectively evaluated. Results Both groups showed statistically significant improvement of all clinical scores from preoperative interval to 5-year follow-up. There was a significant improvement for the International Knee Documentation Committee subjective score from preoperative to 5-year follow-up (Wilcoxon test, P < .001). In the microfracture group, the International Knee Documentation Committee objective score increased from 2.5% normal and nearly normal knees before the operation to 75% normal and nearly normal knees at 5-year follow-up, and the subjective score increased from 41.1 ± 12.3 preoperatively to 70.2 ± 14.7 at 5-year follow-up. In the group treated with Hyalograft C, the International Knee Documentation Committee objective score increased from 15% normal and nearly normal knees before the operation to 90% normal and nearly normal knees at 5-year follow-up, and its subjective score increased from 40.5 ± 15.2 preoperatively to 80.2 ± 19.1 at 5-year follow-up (Wilcoxon test, P < .001). When comparing the groups, better improvement of the International Knee Documentation Committee objective (P < .001) and subjective (P = .003) scores was observed in the Hyalograft C group at 5-year follow-up. The return to sports at 2 years was similar in both groups and remained stable after 5 years in the Hyalograft C group; it worsened in the microfracture group. Conclusion Both methods have shown satisfactory clinical outcome at medium-term follow-up. Better clinical results and sport activity resumption were noted in the group treated with second-generation autologous chondrocyte transplantation.

A second-generation autologous chondrocyte implantation approach to the treatment of focal articular cartilage defects

Autologous chondrocyte implantation (ACI) is the most widely used cell-based surgical procedure for the repair of articular cartilage defects. Challenges to successful ACI outcomes include limitation in defect size and geometry as well as inefficient cell retention. Second-generation ACI procedures have thus focused on developing three-dimensional constructs using native and synthetic biomaterials. Clinically significant and satisfactory results from applying autologous chondrocytes seeded in fibrin within a biodegradable polymeric material were recently reported. In the future, third-generation cell-based articular cartilage repair should focus on the use of chondroprogenitor cells and biofunctionalized biomaterials for more extensive and permanent repair.

Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results

Autologous chondrocyte implantation (ACI) is an effective clinical procedure for the regeneration of articular cartilage defects. BioSeed®-C is a second-generation ACI tissue engineering cartilage graft that is based on autologous chondrocytes embedded in a three-dimensional bioresorbable two-component gel-polymer scaffold. In the present prospective study, we evaluated the short-term to mid-term efficacy of BioSeed-C for the arthrotomic and arthroscopic treatment of posttraumatic and degenerative cartilage defects in a group of patients suffering from chronic posttraumatic and/or degenerative cartilage lesions of the knee. Clinical outcome was assessed in 40 patients with a 2-year clinical follow-up before implantation and at 3, 6, 12, and 24 months after implantation by using the modified Cincinnati Knee Rating System, the Lysholm score, the Knee injury and Osteoarthritis Outcome Score, and the current health assessment form (SF-36) of the International Knee Documentation Committee, as well as histological analysis of second-look biopsies. Significant improvement (p < 0.05) in the evaluated scores was observed at 1 and/or 2 years after implantation of BioSeed-C, and histological staining of the biopsies showed good integration of the graft and formation of a cartilaginous repair tissue. The Knee injury and Osteoarthritis Outcome Score showed significant improvement in the subclasses pain, other symptoms, and knee-related quality of life 2 years after implantation of BioSeed-C in focal osteoarthritic defects. The results suggest that implanting BioSeed-C is an effective treatment option for the regeneration of posttraumatic and/or osteoarthritic defects of the knee.