Purpose: To evaluate the safety and efficacy of hylan G-F 20 viscosupplementation in patients with symptomatic osteoarthritis (OA) of the ankle.

Methods: Prospective, multi-center, open study in patients with primary or secondary grade II talocrural OA confirmed by X-ray. At baseline, patients had to score between 50–90 mm on the Patient-completed Ankle OA Pain VAS (0–100 mm). Patients received one intra-articular injection of 2 ml of hylan G-F 20 and were given an option of a second and final 2 ml injection if their pain remained between 50-90 mm on the VAS after 1, 2 or 3 months. Intraarticular injections were placed in the anteromedial portal of the ankle joint as described for ankle arthroscopy. Patients were followed for 6 months after the final injection. As rescue medication, patients could only take paracetamol up to 4 g per day, except on the day of or the day before a study visit.

All treatment emergent adverse events (AEs) were recorded. The primary efficacy endpoint was change from baseline (at final injection) in the Ankle OA Pain VAS at 3 months after the final injection. Secondary endpoints were Ankle OA Pain VAS scores at all other time-points, total Ankle OA Scale, Patient and Physician Global OA Assessment (VAS), and health-related quality of life (SF-36).

Results: Fifty-five patients (33 M; 22 F) were enrolled and received a first injection of hylan G-F 20. Twenty-four patients (44%) received a second injection. The mean age was 41 years (range 19–70). Overall, treatment with hylan G-F 20 was well tolerated. Seventeen patients (31%) had a treatment related AE of the target ankle. All were of mild or moderate intensity, the majority consisting of arthralgia and injection site pain. There was a statistically significant decrease in Ankle OA Pain VAS score from 68.0 mm at Baseline to 33.8 mm at Month 3 (p< 0.001, paired t-test), which was maintained at 6 months follow-up. The decrease was statistically significant at all time points. Patients who received only 1 injection demonstrated a greater decrease at 3 months (−42.5 mm) than patients with 2 injections (−23.5 mm). The secondary efficacy endpoints showed similar results. Of the total study population, 29 patients (53%) were responders (i.e. at least a 50% decrease in ankle OA pain) after 3 months. 64% of patients receiving 1 injection were responders after 3 months. The SF-36 questionnaire showed statistically significant improvements for both the physical and mental component scores at 3 and 6 months follow-up.

Conclusions: Treatment of OA of the ankle with intraarticular hylan G-F 20 injections is well tolerated. Treatment with hylan G-F 20 significantly decreases pain which is maintained for up to 6 months.

The main obstacle for tissue engineering is the difficulty in producing structurally and functionally well-organized tissues from in vitro cultured cells. Thus, on one hand the research is focusing towards bioactive three-dimensional materials (scaffolds) able to stimulate specific cellular processes. In fact the problem exists that cells cultured in scaffolds have great difficulty to adhere and proliferate if they don’t recognize bioactive molecules. In this respect biological polymers are used in the preparation of synthetic matrices to be used as tissue engineering scaffolds. On the other hand biological research is focusing on morphological and functional properties of cells seeded onto bioactive materials to evaluate their viability, adherence and proliferation, fundamental steps for successful tissue engineering. Surgical specimens were treated with type Ia collagenase and cultured in FCS/EGF supplemented DMEM. Cellular characterization was carried out on 3rd passage cells. Fibroblasts were seeded on Matri-cell, a substrate rich in basal lamina constituents, or PVA-gelatin sponges. Pulmonar ovine fibroblasts were also employed to set up the experimental procedures of cell seeding on scaffolds and histological methods. Immunocytochemistry was carried out to evaluate the presence of cytokeratin, fibroblast antigen, S-100 protein, TGF-beta1, fibronectin, type I collagen. Cytochemistry allowed to examine the synthesis of glysosoaminoglycans (Alcian blu method) and glycoproteins (PAS reaction). A fibroblast-like morphology and phenotype were found in the human cells isolated and selected from yellow ligaments. An high expression of fibroblast Ag, fibronectin and type I collagen but low TGF-beta1 and no cytokeratin immunoreaction were observed. A different localization of the detected antigens was found in the isolated fibroblasts depending on the type of substrate: a strong immunoreactive network of collagen I fibres was observed around cells grown on Matri-cell compared to the granular immunoprecipitates observed in the cytoplasm of fibroblasts grown on non coated plastic. Fibronectin was detected mainly at the extracellular level in Matri-cell cultured fibroblasts. Fibroblasts seeded on PVA-gelatin are viable and adherents to the substrates. Alcian blue reaction demonstrated the active production of glysosoaminoglycans both in Matri-cell or PVA-gelatin cultured cells, suggesting that these substrates allow extracellular matrix molecule production

We report on a case of bilateral medial patellar dislocation, studied with hip/knee/ankle TC for evaluation of torsional defects and treated four times with distal derotative femoral osteotomy and cuneiform subtractive osteotomy of the lateral part of the femoral trochlea.

The patient, a woman 18 years of age at the beginning of treatment, presented with femoral neck anteversion of 30° dx and 25° sx referred to the plane passing posteriorly to the distal femoral condyles; the trochlear angle was 140° dx and 144° sx with medial inclination of trochlea due to medial hypoplasia. The patellae were facing medially, and clinically the patient had suffered medial dislocation of the patella several times.

The treatment lasted 4 years: the femoral derotation of 10° was executed by Orthofix monoassial external fixator; the lateral bone wedge removed from the trochlea was about 10 mm and we used reabsorbable nails for fixation.

Current values are 17° of femoral neck anteversion bilaterally, and the trochlear angle is 151° dx and 150° sx. The patient, now 26 years old, has not had any more dislocations and her knees have complete mobility with no pain.

The good result demonstrates the importance of femoral neck anteversion in the genesis of knee disorders. In this case the absence of specific abnormalities of the extensor mechanism (valgus knee, lateralisation of tibial apophyisis) probably caused the hypoplasia of the medial part of the trochlea and the resulting, rare medial patellar dislocation.

Based on the concepts of White and Panjabi of 1990 we have classified vertebral instabilities into congenital and acquired. The congenital instabilities are due to evident bone alterations that bring about mechanical instability, such as in spondylolisthesis and bone defects of formation and segmentation, or are caused by alteration of the elastic stability of the spinal column, such as in ligamental luxation of the Ehlers-Danlos syndrome or neuromuscular asthenia. Acquired vertebral instabilities include the extensive and much discussed issue of degenerative instabilities and secondary instabilities associated with rheumatoid arthritis, traumatic pathology, neoplastic, iatrogenic instabilities, etc.

The spine is a complex structure in elastic equilibrium between functional demand and the physiological resistance of the motor segments, that is the articulations, capsules and ligaments, and the muscles. Like Aulisa and Vinciguerra (1994) we are inclined to refer to stable and unstable equilibrium of the spine and to distinguish “mechanical” stability from “biological” stability. There are authoritative cases of evident macro-instability where the functional units, even though affected by serious mechanical alteration, are able to conserve a totally asymptomatic vertebral column in a state of elastic compensation for a long time.

We have classified our cases according to Christian Pfirrmann’s classification of lumbar intervertebral disc degeneration (2001), completing it with the three types of disc degeneration that Modic suggested in 1998. We present our case histories from 2001 to 2002 of macro-instabilities of lumbo-sacral spine treated with stabilisation, PLIF and fusion and of micro-instabilities treated with dynamic stabilisation in neutralisation without fusion.

In instabilities when one or more motor segments do not respond to permanent stress and the discs begin to change structurally and demonstrate phenomena of fissuring and dehydration, to the point of assured degeneration and collapse, we have developed a two-fold method of treatment:

MICRO-INSTABILITY: when the degenerative phenomena are still in progress and TAC, RMN and functional radiographs can identify an early phase, we propose dynamic stabilisation in neutralisation in order to restore the height of the disc and cancel the disc-radicular conflict, thus maintaining the capacity of movement of the functional unit.