Francesco Benazzo

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

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.

Similar histopathological picture in males with Achilles and patellar tendinopathy.

PURPOSE To ascertain whether there are differences in the histopathological appearance of tendinopathic Achilles and patellar tendons. METHODS In males, we studied biopsies from tendinopathic Achilles (N = 28; average age 34.1 yr) and patellar tendons (N = 28; average age 32.1), Achilles tendons (N = 21; average age 61.8 yr) from deceased patients with no known tendon pathology, and patellar tendons (N = 15; average age 28.3) from patients undergoing anterior cruciate ligament reconstruction. Hematoxylineosin stained slides were interpreted using a semiquantitative grading scale (0: normal to 3: maximally abnormal) for fiber structure, fiber arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, and hyalinization. All slides were assessed blindly twice, the agreement between two readings ranging from 0.170 to 0.750 (kappa statistics). RESULTS The highest mean score of tendinopathic Achilles tendons was not significantly different from that of tendinopathic patellar tendons (11.6 +/- 5 and 10.4 +/- 3, respectively). The ability to differentiate between an Achilles tendon and a patellar tendon was low. CONCLUSIONS Tendinopathic Achilles and patellar tendons show a similar histological picture. It was not possible to identify whether a specimen had been harvested from an Achilles or a patellar tendon on the basis of histological examination. The general pattern of degeneration was common to both tendinopathic Achilles and patellar tendons. A common, as yet unidentified, etiopathological mechanism may have acted on both these tendon populations.

Surgery for chronic achilles tendinopathy yields worse results in nonathletic patients

ObjectiveTo report the outcome of surgery for chronic recalcitrant Achilles tendinopathy in nonathletic and athletic subjects. DesignCase-control study. SettingUniversity teaching hospitals. PatientsWe matched each of the 61 nonathletic patients with a diagnosis of tendinopathy of the Achilles tendon with an athletic patient with tendinopathy of the main body of the Achilles tendon of the same sex and age (±2 years). A match was possible for 56 patients (23 males and 33 females). Forty-eight nonathletic subjects and 45 athletic subjects agreed to participate. InterventionsOpen surgery for Achilles tendinopathy. Main Outcome MeasureOutcome of surgery, return to sport, complication rate. ResultsNonathletic patients were shorter and heavier than athletic patients. They had greater body mass index, calf circumference, side-to-side calf circumference differences, and subcutaneous body fat than athletic patients. Of the 48 nonathletic patients, 9 underwent further surgery during the study period, and only 25 reported an excellent or good result. Of the 45 athletic subjects, 4 underwent further surgery during the study period, and 36 reported an excellent or good result. The remaining patients could not return to their normal levels of activity. In all of them, pain significantly interfered with daily activities. ConclusionsNonathletic subjects experience more prolonged recovery, more complications, and a greater risk of further surgery than athletic subjects with recalcitrant Achilles tendinopathy.

Human adipose-derived stem cells (hASCs) proliferate and differentiate in osteoblast-like cells on trabecular titanium scaffolds

The use of stem cells in regenerative medicine is an appealing area of research that has received a great deal of interest in recent years. The population called human adipose tissue-derived stem cells (hASCs) share many of the characteristic of its counterpart of marrow including extensive proliferative potential and the ability to undergo multilineage differentiation along classical mesenchymal lineages: adipogenesis, chondrogenesis, osteogenesis, and myogenesis. The aim of this study was to evaluate with biochemical and morphological methods the adhesion and differentiation of hASCs grown on trabecular titanium scaffolds. The hASCs isolated from subcutaneous adipose tissue after digestion with collagenase were seeded on monolayer and on trabecular titanium scaffolds and incubated at 37 degrees C in 5% CO(2) with osteogenic medium or control medium.The results showed that hASCs were able to adhere to titanium scaffolds, to proliferate, to acquire an osteoblastic-like phenotype, and to produce a calcified extracellular matrix with protein, such as, decorin, fibronectin, osteocalcin, osteonectin, osteopontin, and type I collagen. These data suggest that this kind of scaffold/cells construct is effective to regenerate damaged tissue and to restore the function of bone tissue.

Use of capacitive coupled electric fields in stress fractures in athletes

The authors report the results of an open study on the treatment of stress fracture in athletes by capacitive coupling, a bone healing stimulation method promoting bone formation by application of alternating current in the form of a sinusoidal wave. Twenty-five lower-limb (navicular, 2nd and 5th metatarsal, tibia, fibula, and talus) stress fractures in 21 athletes (mean age, 21.8 years old) were treated. The mean stimulation time was 52 days (navicular fractures, 60 days). Twenty-two fractures were healed, 1 was not healed, and 2 were improved. This preliminary report shows that capacitive coupling can be used safely in the treatment of these stress fractures.

The differentiation of human adipose-derived stem cells (hASCs) into osteoblasts is promoted by low amplitude, high frequency vibration treatment

Several studies have demonstrated that tissue culture conditions influence the differentiation of human adipose-derived stem cells (hASCs). Recently, studies performed on SAOS-2 and bone marrow stromal cells (BMSCs) have shown the effectiveness of high frequency vibration treatment on cell differentiation to osteoblasts. The aim of this study was to evaluate the effects of low amplitude, high frequency vibrations on the differentiation of hASCs toward bone tissue. In view of this goal, hASCs were cultured in proliferative or osteogenic media and stimulated daily at 30Hz for 45min for 28days. The state of calcification of the extracellular matrix was determined using the alizarin assay, while the expression of extracellular matrix and associated mRNA was determined by ELISA assays and quantitative RT-PCR (qRT-PCR). The results showed the osteogenic effect of high frequency vibration treatment in the early stages of hASC differentiation (after 14 and 21days). On the contrary, no additional significant differences were observed after 28days cell culture. Transmission Electron Microscopy (TEM) images performed on 21day samples showed evidence of structured collagen fibers in the treated samples. All together, these results demonstrate the effectiveness of high frequency vibration treatment on hASC differentiation toward osteoblasts.

An Operative Approach to Achilles Tendinopathy

Summary: Achilles tendinopathy is one of the most common overuse problems in running athletes. When conservative management is unsuccessful, surgery is indicated to increase the likelihood that the patient will return to high levels of sporting activity. Circulatory, metabolic, and mechanical factors are involved in the pathogenesis of the tendinopathy. In surgery for chronic paratendinopathy, we use different techniques depending on the extension of the adhesions and the thickening of the paratenon, removing the fibrotic rinds of the fascia and the hypertrophic parts of the paratenon, taking care not to disturb the mesotendon. In paratendinopathy associated with tendinopathy of the main body of the tendon and in isolated tendinopathy of the main body of the tendon, we free the tendon from fibrotic adhesions and remove the degenerated nodules. Longitudinal tenotomies are performed to try to re-establish tendon nutrition, or at least to cause tendon scarring. Moreover, to improve the blood supply in tendons with extensive degeneration, we have started to place a bundle of soleus muscle within the tendon itself. In insertional tendinopathy, the pre-Achilles bursa is removed, together with the lateral and medial outgrowth of bone and cartilage of the posterior border of the calcaneus, as is done with Haglund deformity, thus preventing further impingement of the tendon insertion.

Effects of electromagnetic stimulation on osteogenic differentiation of human mesenchymal stromal cells seeded onto gelatin cryogel.

Bone tissue engineering typically uses biomaterial scaffolds, osteoblasts or cells that can become osteoblasts, and biophysical stimulations to promote cell attachment and differentiation. In this study, we investigated the effects of an electromagnetic wave on mesenchymal stromal cells isolated from the bone marrow and seeded upon gelatin cryogel disks. In comparison with control conditions without electromagnetic stimulus, the electromagnetic treatment (magnetic field, 2 mT; frequency, 75 Hz) increased the cell proliferation and differentiation and enhanced the biomaterial surface coating with bone extracellular matrix proteins. Using this tissue-engineering approach, the gelatin biomaterial, coated with differentiated cells and their extracellular matrix proteins, may be used in clinical applications as an implant for bone defect repair.

In vitro electromagnetically stimulated SAOS-2 osteoblasts inside porous hydroxyapatite

One of the key challenges in reconstructive bone surgery is to provide living constructs that possess the ability to integrate in the surrounding tissue. Bone graft substitutes, such as autografts, allografts, xenografts, and biomaterials have been widely used to heal critical-size long bone defects due to trauma, tumor resection, congenital deformity, and tissue degeneration. In particular, porous hydroxyapatite is widely used in reconstructive bone surgery owing to its biocompatibility. In addition, the in vitro modification of hydroxyapatite with osteogenic signals enhances the tissue regeneration in vivo, suggesting that the biomaterial modification could play an important role in tissue engineering. In this study we have followed a biomimetic strategy where electromagnetically stimulated SAOS-2 human osteoblasts proliferated and built their extracellular matrix inside a porous hydroxyapatite scaffold. The electromagnetic stimulus had the following parameters: intensity of the magnetic field equal to 2 mT, amplitude of the induced electric tension equal to 5 mV, frequency of 75 Hz, and pulse duration of 1.3 ms. In comparison with control conditions, the electromagnetic stimulus increased the cell proliferation and the surface coating with bone proteins (decorin, osteocalcin, osteopontin, type-I collagen, and type-III collagen). The physical stimulus aimed at obtaining a better modification of the biomaterial internal surface in terms of cell colonization and coating with bone matrix.

Electromagnetic enhancement of a culture of human SAOS-2 osteoblasts seeded onto titanium fiber-mesh scaffolds

The surface properties of a biomaterial are fundamental to determine the response of the host tissue. In the present study, we have followed a particular biomimetic strategy where electromagnetically stimulated SAOS-2 human osteoblasts proliferated and built a calcified extracellular matrix on a titanium fiber-mesh surface. In comparison with control conditions, the electromagnetic stimulation (magnetic field intensity, 2 mT; frequency, 75 Hz) caused higher cell proliferation and increased surface coating with type-I collagen, decorin, and osteopontin (9.8-fold, 11.3-fold, and 9.5-fold, respectively). Reverse transcriptase-polymerase analysis revealed the electromagnetically upregulated transcription specific for the foregoing matrix proteins and for the growth factor TGF-beta1. The immunofluorescence of type-I collagen, decorin, and osteopontin showed their colocalization in the cell-rich areas. The use of an electromagnetic bioreactor aimed at obtaining the surface modification of the biocompatible metallic scaffold in terms of cell colonization and coating with calcified extracellular matrix. The superficially modified biomaterial could be used, in clinical applications, as an implant for bone repair.