Maurilio Marcacci

Repair of Large Bone Defects with the Use of Autologous Bone Marrow Stromal Cells

To the Editor: The reconstruction of large bone segments is an important clinical problem, and none of the approaches proposed thus far have proved very effective. In animals, repair and functional...

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 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.

A novel route in bone tissue engineering: Magnetic biomimetic scaffolds

In recent years, interest in tissue engineering and its solutions has increased considerably. In particular, scaffolds have become fundamental tools in bone graft substitution and are used in combination with a variety of bio-agents. However, a long-standing problem in the use of these conventional scaffolds lies in the impossibility of re-loading the scaffold with the bio-agents after implantation. This work introduces the magnetic scaffold as a conceptually new solution. The magnetic scaffold is able, via magnetic driving, to attract and take up in vivo growth factors, stem cells or other bio-agents bound to magnetic particles. The authors succeeded in developing a simple and inexpensive technique able to transform standard commercial scaffolds made of hydroxyapatite and collagen in magnetic scaffolds. This innovative process involves dip-coating of the scaffolds in aqueous ferrofluids containing iron oxide nanoparticles coated with various biopolymers. After dip-coating, the nanoparticles are integrated into the structure of the scaffolds, providing the latter with magnetization values as high as 15 emu g(-)(1) at 10 kOe. These values are suitable for generating magnetic gradients, enabling magnetic guiding in the vicinity and inside the scaffold. The magnetic scaffolds do not suffer from any structural damage during the process, maintaining their specific porosity and shape. Moreover, they do not release magnetic particles under a constant flow of simulated body fluids over a period of 8 days. Finally, preliminary studies indicate the ability of the magnetic scaffolds to support adhesion and proliferation of human bone marrow stem cells in vitro. Hence, this new type of scaffold is a valuable candidate for tissue engineering applications, featuring a novel magnetic guiding option.

Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial

BackgroundPlatelet Rich Plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA).Methods109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age> 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded.ResultsOnly minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2).ConclusionsResults suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

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 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.

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.