E. Kon

Articular cartilage engineering with Hyalograft® C: 3-Year clinical results

The use of tissue engineering for cartilage repair has emerged as a potential therapeutic option and has led to the development of Hyalograft® C, a tissue-engineered graft composed of autologous chondrocytes grown on a scaffold entirely made of HYAFF® 11, an esterified derivative of hyaluronic acid. Here we present the results of an ongoing multicenter clinical study conducted with the primary objective to investigate the subjective symptomatic, functional and health-related quality of life outcomes of patients treated with Hyalograft® C. Clinical results on the cohort of 141 patients with followup assessments ranging from 2 to 5 years (average followup time: 38 months), are reported. At followup 91.5% of patients improved according to the International Knee Documentation Committee subjective evaluation; 76% and 88% of patients had no pain and mobility problems respectively assessed by the EuroQol-EQ5D measure. Furthermore, 95.7% of the patients had their treated knee normal or nearly normal as assessed by the surgeon; cartilage repair was graded arthroscopically as normal or nearly normal in 96.4% of the scored knees; the majority of the second-look biopsies of the grafted site histologically were assessed as hyalinelike. Importantly, a very limited complication rate was recorded in this study. The positive clinical results obtained indicate that Hyalograft® C is a safe and effective therapeutic option for the treatment of articular cartilage lesions. Level of Evidence: Therapeutic study, Level III-2 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Arthroscopic autologous condrocyte transplantation: technical note

Abstract.We describe an arthroscopic surgical technique for tissue engineered cartilage grafting. A three-dimensional hyaluronic acid support is used for autologous chondrocyte culturing. The technique reduces morbidity of classic autologous implant and avoids open surgery and the use of a periosteal flap. The procedure includes the advantages of arthroscopic osteochondral grafting without donor site morbidity. With this technique is possible to reduce the patient morbidity, time and cost of surgery.

Comparative evaluation of autologous chondrocyte implantation and mosaicplasty: a multicentered randomized clinical trial.

Objective:To compare the respective performance and effectiveness of autologous chondrocyte implantation (ACI) and mosaicplasty at resurfacing local full-thickness chondral defects of the knee. Design:Randomized clinical trial. Setting:Multicenter trial at orthopedic clinics and university hospitals conducted from 1997 to 2000. Patients:A population of patients selected according to eligibility criteria of age, traumatic origin of the defect, its localization, size, and gravity, and above all, no previous surgical treatment of the lesion. Forty-seven patients were randomly assigned to ACI or mosaicplasty and subjected to arthroscopic debridement of the lesion at the time of enrollment. They were called for surgery 6 months after the initial debridement. Main Outcome:Improved knee functionality as assessed by repeated clinical evaluation based on the International Knee Documentation Committee Scale and the Lysholm Knee Scoring Scale. Results:Fourteen patients (31.8%) experienced substantial improvement following the initial debridement and, being clinically cured, received no further treatment. Seven patients (15.9%) were lost to follow-up. Among the 23 patients (52.3%) who could effectively be evaluated, a complete recovery (ie, Lysholm Knee Scoring Scale score, 90-100) was observed upon clinical examination in 88% of the mosaicplasty-treated patients and in 68% of the ACI-treated ones (P = 0.093). Conclusions:Although the low power of our study prevents definitive conclusions, ACI and mosaicplasty are cartilage repair techniques that are clinically equivalent and similar in performance. The high percentage of spontaneous improvement (⅓ of the patients) observed after simple debridement calls into question the need for prompt surgical treatment of patients with lesions similar to those included in this clinical trial. Moreover, this finding warrants further investigation, ideally through randomized clinical trials in which patients subjected to debridement alone are compared with patients undergoing reconstructive surgery.

Patellofemoral Full-Thickness Chondral Defects Treated With Hyalograft-C A Clinical, Arthroscopic, and Histologic Review

Background Tissue engineering has emerged as a potential therapeutic option for cartilage regeneration. Hypothesis Hyaluronan-based scaffolds seeded with autologous chondrocytes are a viable treatment for damaged articular surface of the patellofemoral joint. Study Design Case series; Level of evidence, 4. Methods Thirty-two chondral lesions with a mean size of 4.7 cm2 were treated with Hyalograft-C. Twenty-two lesions were located in the patella and 10 in the trochlea. Sixteen patients had previous trauma, 3 had osteochondritis dissecans, and 13 had degenerative changes. Transplantations were carried out arthroscopically or through a miniarthrotomy incision. Eight patients had concomitant procedures, including patellar realignment (2), lateral release (3), and meniscectomy (3). Results were evaluated using the International Cartilage Repair Society–International Knee Documentation Committee scale, EuroQol EQ-5D form, and magnetic resonance imaging scans at 12 and 24 months. Six patients had second-look arthroscopy and biopsies. Statistical analysis was performed using the paired ttest and Wilcoxon signed rank test. Results The International Cartilage Repair Society–International Knee Documentation Committee and EuroQol EQ-5D scores demonstrated a statistically significant improvement (P <. 0001). Objective preoperative data improved from 6/32 (18.8%) with International Knee Documentation Committee A or B to 29/32 (90.7%) at 24 months after transplantation. Mean subjective scores improved from 43.2 points preoperatively to 73.6 points 24 months after implantation. Magnetic resonance imaging studies at 24 months revealed 71% to have an almost normal cartilage with positive correlation to clinical outcomes. Second-look arthroscopies in 6 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance. Conclusion Biodegradable scaffolds seeded with autologous chondrocytes can be a viable treatment for chondral lesions. The type of tissue repair achieved demonstrated histologic characteristics similar to normal articular cartilage. Long-term investigations are needed to determine the durability of the repair produced with this technique.

A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions: Technique note and an early stability pilot clinical trial

INTRODUCTIONnOsteochondral articular defects are a key concern in orthopaedic surgery. Current surgical techniques to repair osteochondral defects lead to poor subchondral bone regeneration and fibrocartilage formation, which is often associated with joint pain and stiffness. The objective of this pilot clinical study is to evaluate the performance and the intrinsic stability of a newly developed biomimetic osteochondral scaffold and to test the safety and the feasibility of the surgical procedure.nnnMETHODSnA gradient composite osteochondral scaffold based on type I collagen-hydroxyapatite was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Thirteen patients (15 defect sites) were treated with scaffold implantation from January 2007 to July 2007: four at the medial femoral condyle, two at the lateral femoral condyles, five at the patellas and four at the trochleas. The mean size of the defects was 2.8 cm(2) (range: 1.5-5.9 cm(2)). All patients were followed up prospectively. High-resolution magnetic resonance imaging (MRI) was used to determine the early postoperative adherence rate at 4-5 weeks and 25-26 weeks after scaffold implantation. Moreover, the magnetic resonance observation of cartilage repair tissue (MOCART) score was performed on every MRI. Two second-looks were performed at 6 months; cartilage repair was assessed using the International Cartilage Repair Society (ICRS) visual scoring system and histological and immunohistochemical analysis of the two biopsies was carried out.nnnRESULTSnA completely attached graft and repair tissue were found in 13 of 15 lesions (86.7%). A partial detachment was observed in two patients (13.3%). No detached grafts were found. Complete filling of the cartilage defect and congruency of the articular surface were seen in 10 lesions (66.7%) with MRI evaluation at 6 months. The complete integration of the grafted cartilage was detected in eight lesions (53.3%). Subchondral bone changes (oedema or sclerosis) were found in eight defects (53.3%). Statistical analysis showed a significant improvement in the International Knee Documentation Committee (IKDC) subjective and objective scores from preoperative to 6 months follow-up (p<0.0005). Visual scoring of the repaired tissue at second-look revealed a normal repair score in one case and a near-normal repair score in the other case. Histological analysis showed the formation of subchondral bone without the presence of biomaterial. The cartilage repair tissue appeared to be engaged in an ongoing maturation process.nnnCONCLUSIONSnThe technique is safe and MRI evaluation at short-term follow-up has demonstrated good stability of the scaffold without any other fixation device. The preliminary clinical results at short-term follow-up are encouraging. A clinical and MRI study with longer follow-up and randomised studies will be done to confirm the high potential of this novel osteochondral scaffold.

Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures.

AbstractYoung patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide short-term pain relief but are only palliative in nature. Joint replacement, a successful procedure in the older population, is controversial in younger patients, who are less satisfied and experience higher failure rates. Therefore, while traditionally not indicated for the treatment of OA, cartilage repair has become a focus of increased interest due to its potential to provide pain relief and alter the progression of degenerative disease, with the hope of delaying or obviating the need for joint replacement. This review of cartilage repair techniques will discuss currently available procedures, specifically pertaining to experiences in the setting of early OA.n Level of evidence IV.

Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration

PurposeThe aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP).MethodsAll in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet-rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells).ResultsFifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration.ConclusionsBesides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra-articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short-term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.Level of evidenceIV.

Disease-specific clinical problems associated with the subchondral bone

The subchondral bone is involved in a variety of diseases affecting both the articular cartilage and bone. Osteochondral defects in distinct locations and of variable sizes are the final results of different etiologies. These include traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Traumatic osteochondral defects are caused by osteochondral fractures, separating an osteochondral fragment that includes articular cartilage and both subchondral and trabecular bone from the joint surface. In osteochondritis dissecans, the disease originates in the subchondral bone and secondarily affects the articular cartilage. Location, stage, size, and depth of osteochondral lesions play a role in the treatment of traumatic osteochondral defects and osteochondritis dissecans. Surgical options include fragment refixation, transplantation of osteochondral autografts, or bone restoration by impacted cancellous bone grafts combined with autologous chondrocyte transplantation. An insufficiency fracture of the subchondral bone may be the initiating factor of what was formerly believed to be a spontaneous osteonecrosis of the knee (SPONK). Recent histopathological studies suggest that each stage of SPONK reflects different types of bone repair reactions following a fracture of the subchondral bone plate. Osteoarthritis is a disease that does affect not only the articular cartilage, but also the subchondral bone. Reconstructive surgical techniques aim at preserving joint function, inducing fibrocartilaginous repair, and at correcting malalignment. This review summarizes the current status of the clinical treatment of traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis as they affect the subchondral bone region and its adjacent structures.

Intra- and extra-articular anterior cruciate ligament reconstruction utilizing autogeneous semitendinosus and gracilis tendons: 5-year clinical results

Abstract. This prospective study examined 50 patients who underwent ACL surgery using hamstring tendons with a modification including intra- and extra-articular reconstruction. All patients were athletes competing at a high level in various sports. Full return to sports was allowed at 4xa0months. IKDC score and KT-2000 were used for assessing clinical outcome at a mean of 6.4xa0years (5–7xa0years) Resumption of sport, Tegner activity score, and isokinetic test were also used. The IKDC score showed 92% of normal or nearly normal knees. Of the 50 patients 48 regained full extension, and only two had extension deficit between 0° and 3°. KT evaluation was less than 3xa0mm in 38 cases (76%), 3–5xa0mm in 9 (18%), and more than 5xa0mm in 3 (6%). In 90% of cases the patient resumed sport at the same level. The mean Tegner activity score was 8.1 (5–10). The isokinetic test showed no deficit for hamstring and quadriceps muscles. Removal of staples was necessary in eight cases (16%) due to femoral lateral bursitis. Acute reconstruction had significantly better clinical assessment of abnormal laxity and KT value. Men had significantly better results then women. This technique demonstrated a high reliability, low morbidity, low functional deficit and fast recovery using hamstring grafts.

Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up

OBJECTIVEnTo evaluate the clinical outcome of hyaluronan-based arthroscopic autologous chondrocyte transplantation at a minimum of 5 years of follow-up and to correlate it with the MRI evaluation parameters.nnnMETHODSnFifty consecutive patients were included in the study and evaluated clinically using the Cartilage Standard Evaluation Form as proposed by ICRS and the Tegner score. Forty lesions underwent MRI evaluation at a minimum 5-year follow-up. For the description and evaluation of the graft, we employed the MOCART-scoring system.nnnRESULTSnA statistically significant improvement in all clinical scores was observed at 2 and over 5 years. The total MOCART score and the signal intensity (3D-GE-FS) of the repair tissue were statistically correlated to the IKDC subjective evaluation. Larger size of the treated cartilage lesions had a negative influence on the degree of defect repair and filling, the integration to the border zone and the subchondral lamina integrity, whereas more intensive sport activity had a positive influence on the signal intensity of the repair tissue, the repair tissue surface, and the clinical outcome.nnnCONCLUSIONnOur findings confirm the durability of the clinical results obtained with Hyalograft C and the usefulness of MRI as a non-invasive method for the evaluation of the repaired tissue and the outcome after second-generation autologous transplantation over time.