Marco Delcogliano

Arthroscopic second-generation autologous chondrocyte implantation compared with microfracture for chondral lesions of the knee: prospective nonrandomized study at 5 years.

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.

Platelet-riCh plasma: New clinical application A pilot study for treatment of jumper's knee

This study describes a simple, low-cost, minimally invasive way to apply PRP growth factors to chronic patellar tendinosis; 20 male athletes with a mean history of 20.7 months of pain received treatment, and outcomes were prospectively evaluated at 6 months follow-up. No severe adverse events were observed, and statistically significant improvements in all scores were recorded. The results suggest that this method may be safely used for the treatment of jumpers knee, by aiding the regeneration of tissue which otherwise has low healing potential.

Patellofemoral Full-Thickness Chondral Defects Treated With Second-Generation Autologous Chondrocyte Implantation Results at 5 Years' Follow-up

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.

Arthroscopic Autologous Osteochondral Grafting for Cartilage Defects of the Knee Prospective Study Results at a Minimum 7-Year Follow-up

Background Articular cartilage lesions, with their inherent limited healing potential, remain a challenging problem for orthopaedic surgeons. Various approaches have been proposed to treat these lesions; nevertheless, opinions on indications and clinical efficacy of these techniques are still controversial. Purpose To evaluate the outcome of osteochondral autografts for treatment of femoral condyle cartilage lesions at a medium-to long-term follow-up. Study Design Case series; Level of evidence, 4. Methods We prospectively evaluated 30 patients (mean age, 29.3 years) with full-thickness knee chondral lesions (<2.5 cm2) treated with arthroscopic autologous osteochondral transplantation. Thirteen patients underwent previous surgery, while 17 patients were operated on for the first time. In 19 patients, associated procedures were performed. All patients were evaluated at 2- and 7-year follow-up. The International Cartilage Repair Society form, Tegner score, and magnetic resonance imaging were used for clinical evaluation. Results The International Cartilage Repair Society objective evaluation showed 76.7% of patients had good or excellent results at 7-year follow-up, and International Knee Documentation Committee subjective score significantly improved from preoperative (34.8) to 7-year follow-up (71.8). The Tegner evaluation showed a significant improvement after the surgery at 2- and 7-year follow-up (from 2.9 to 6.2 and 5.6, respectively); however, we noticed reduced sports activity from 2- to 7-year follow-up. Magnetic resonance imaging evaluation showed good integration of the graft in the host bone and complete maintenance of the grafted cartilage in more than 60% of cases. Conclusion The results of this technique at medium- to long-term follow-up are encouraging. This arthroscopic 1-step surgery appears to be a valid solution for treatment of small, grade III to IV cartilage defects.

Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial.

The objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A new multilayer gradient nano‐composite scaffold was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. In the femoral condyles of 12 sheep, 24 osteochondral lesions were created. Animals were randomized into three treatment groups: scaffold alone, scaffold colonized in vitro with autologous chondrocytes and empty defects. Six months after surgery, the animals were sacrificed and the lesions were histologically evaluated. Histologic and gross evaluation of specimens showed good integration of the chondral surface in all groups except for the control group. Significantly better bone regeneration was observed both in the group receiving the scaffold alone and in the group with scaffold loaded with autologous chondrocytes. No difference in cartilage surface reconstruction and osteochondral defect filling was noted between cell‐seeded and cell‐free groups. In the control group, no bone or cartilage defect healing occurred, and the defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The results of the present study showed that this novel osteochondral scaffold is safe and easy to use, and may represent a suitable matrix to direct and coordinate the process of bone and hyaline‐like cartilage regeneration. The comparable regeneration process observed with or without autologous chondrocytes suggests that the main mode of action of the scaffold is based on the recruitment of local cells.

Matrix-Assisted Autologous Chondrocyte Transplantation for the Repair of Cartilage Defects of the Knee Systematic Clinical Data Review and Study Quality Analysis

Background The clinical application of the second-generation tissue-engineering approach for the treatment of cartilage lesions has been documented for different types of scaffolds, but systematic information on clinical efficacy and long-term results is not available. Purpose To analyze and assess the quality of clinical studies on different products in the emerging field of matrix-assisted auto-logous chondrocyte transplantation. The secondary purpose of this review was to improve the quality assessment of studies by modifying the Coleman methodology score (CMS). Study Design Systematic review. Methods For this review, a literature search was performed to identify all published and unpublished clinical studies of matrixassisted (second-generation) autologous chondrocyte transplantation using the following medical electronic databases: MED-LINE, MEDLINE preprints, EMBASE, CINAHL, Life Science Citations, and British National Library of Health, including the Cochrane Central Register of Controlled Trials (CENTRAL). The search period was January 1, 1995, to July 1, 2008. To better assess cartilage-related studies, a modification of the CMS was proposed. Results Eighteen studies were included in the analysis, reporting on 731 patients with an average follow-up of 27.3 months (6.5-60.0 months). Of the 18 studies, 2 were randomized controlled studies, 3 were prospective comparative studies, 11 were prospective cohort studies or prospective case series, and 2 were retrospective case series. Original CMSs for these studies (55.1 6 1.6) were significantly higher than those of cartilage repair studies in general (43.5 6 1.6, P <.0001) reported in 2005. The statistical analysis indicated that the modified CMS showed higher correlations and lower variability of correlations among 3 reviewers. Conclusion The quality of the currently available data on second-generation autologous chondrocyte transplantation is still limited by study designs. The modified CMS has demonstrated better sensitivity and reproducibility with respect to the original score, so it can be recommended for cartilage clinical studies evaluation.

Novel Nano-composite Multilayered Biomaterial for Osteochondral Regeneration A Pilot Clinical Trial

Background: In recent years, there has been an increasing interest in and awareness of the importance of subchondral bone, for its role in the pathogenesis of articular surface damage and for the care that should be taken when treating such damage. Purpose: The objective of this pilot clinical study was to test the safety and performance of a newly developed type I collagen-hydroxyapatite nanostructured biomimetic osteochondral scaffold that aims to regenerate cartilage and subchondral bone. Study Design: Case series; Level of evidence, 4. Methods: A multilayer gradient nano-composite scaffold was obtained by nucleating collagen type I fibrils with hydroxyapatite nanoparticles. Thirty patients (9 female, 21 male; mean age, 29.3 years) with knee chondral or osteochondral lesions were treated with scaffold implantation. Lesion size varied from 1.5 cm2 to 6.0 cm2. Twenty-eight patients were followed for 2 years and were clinically evaluated using the International Knee Documentation Committee and Tegner scores. At final follow-up, magnetic resonance imaging evaluation was performed in 24 patients, and they were evaluated with the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score. Results: The Tegner and International Knee Documentation Committee objective and subjective scores improved significantly from the baseline evaluation to the 6-, 12-, and 24-month follow-ups. Further analysis showed a slower recovery but the same results for patients who presented with adverse events, for older patients, for patients who underwent previous surgery, and for those with patellar lesions. In contrast, a faster recovery was observed in active patients. At magnetic resonance imaging evaluation, complete filling of the cartilage and complete integration of the graft was shown in 70% of the lesions. However, the subchondral lamina and bone were considered intact in a minority of cases (7% and 47%, respectively). Conclusion: This open 1-step procedure was used for the treatment of chondral and osteochondral knee defects. The present pilot study highlighted the safety and potential clinical benefit of the graded biomimetic osteochondral scaffold in promoting bone and cartilage tissue restoration by itself and with good clinical and magnetic resonance imaging results at the 2-year follow-up.

Tissue engineering for total meniscal substitution : Animal study in sheep model

OBJECTIVE The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated. METHODS Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology. RESULTS All implants showed excellent capsular ingrowth at the periphery. Macroscopically, no difference was observed between cell-seeded and cell-free groups. Better implant appearance and integrity was observed in the group without transosseous horns fixation. Using the latter implantation technique, lower joint degeneration was observed in the cell-seeded group with respect to cell-free implants. The histological analysis indicated cellular infiltration and vascularization throughout the implanted constructs. Cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. CONCLUSION The current study supports the potential of a novel HYAFF/polycaprolactone scaffold for total meniscal substitution. Seeding of the scaffolds with autologous chondrocytes provides some benefit in the extent of fibrocartilaginous tissue repair.

Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model

BackgroundCurrent research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-rich plasma (PRP) to enhance the repair process of a collagen-hydroxyapatite scaffold in osteochondral defects in a sheep model.MethodsPRP was added to a new, multi-layer gradient, nanocomposite scaffold that was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Twenty-four osteochondral lesions were created in sheep femoral condyles. The animals were randomised to three treatment groups: scaffold, scaffold loaded with autologous PRP, and empty defect (control). The animals were sacrificed and evaluated six months after surgery.ResultsGross evaluation and histology of the specimens showed good integration of the chondral surface in both treatment groups. Significantly better bone regeneration and cartilage surface reconstruction were observed in the group treated with the scaffold alone. Incomplete bone regeneration and irregular cartilage surface integration were observed in the group treated with the scaffold where PRP was added. In the control group, no bone and cartilage defect healing occurred; defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed.ConclusionsThe hydroxyapatite-collagen scaffold enhanced osteochondral lesion repair, but the combination with platelet growth factors did not have an additive effect; on the contrary, PRP administration had a negative effect on the results obtained by disturbing the regenerative process. In the scaffold + PRP group, highly amorphous cartilaginous repair tissue and poorly spatially organised underlying bone tissue were found.

Does Intensive Rehabilitation Permit Early Return to Sport Without Compromising the Clinical Outcome After Arthroscopic Autologous Chondrocyte Implantation in Highly Competitive Athletes

Background Despite improvement in treatment for articular cartilage lesions, prolonged recovery still precludes early return to competitive sports. The challenge of postoperative rehabilitation is to optimize return to preinjury activities without jeopardizing the graft. Hypothesis Intensive rehabilitation after second-generation arthroscopic autologous cartilage implantation (Hyalograft C) facilitates graft maturation and safely allows for early return to competition without jeopardizing clinical outcome at longer follow-up. Study Design Cohort study; Level of evidence, 3. Methods The outcome of 31 competitive male athletes with International Cartilage Repair Society grade III-IV cartilaginous lesions of the medial or lateral femoral condyle or trochlea were evaluated at 1-, 2-, and 5-year follow-up. The athletic cohort was compared with a similar control cohort of 34 nonathletic patients who were treated with autologous chondrocyte implantation. The athletic cohort followed a 4-phase intensive rehabilitation protocol. Eleven of the patients in this cohort were also treated with an isokinetic exercise program and on-field rehabilitation. The patients in the control cohort completed only phase 1 of rehabilitation. Results When comparing the 2 groups, a greater improvement in the group of athletes was achieved at 5-year follow-up (P = .037) in the self-assessment of quality of life and International Knee Documentation Committee subjective evaluation at 12 months and at 5 years of follow-up (P = .001 and P = .002, respectively). When analyzing the return to sports activity, 80.6% of the athletes returned to their previous activity level in 12.4 ± 1.6 months; athletes treated with the on-field rehabilitation and isokinetic exercise program had faster recovery and an even earlier return to competition (10.6 ± 2.0 months). Conclusion For optimal results, autologous chondrocyte implantation rehabilitation should not only follow but also facilitate the process of graft maturation. Intensive rehabilitation may safely allow a faster return to competition and also influence positively the clinical outcome at medium-term follow-up.