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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 341 - 341
1 May 2010
Franceschi F Longo UG Ruzzini L Dicuonzo G Maffulli N Denaro V
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Postoperative stiffness (POS) of the shoulder may occur after an apparently successful reconstruction of a rotator cuff tear.

The role of the peripheral nervous system in tissue healing has only recently been recognized.

We determined the plasma levels of SP in patients with postoperative stiffness after arthroscopic repair of a rotator cuff tear, and compared them with those in patients with a good outcome after arthroscopic rotator cuff repair.

Plasma samples were obtained at 15 months from surgery from 2 groups of patients who underwent arthroscopic repair of a rotator cuff tear. In Group 1, 30 subjects (14 men and 16 women, mean age: 64.6 years, range 47 to 78) with shoulder stiffness 15 months after arthroscopic rotator cuff repair were recruited. In Group 2, 30 patients (11 men and 19 women, mean age: 57.8 years, range 45 to 77) were evaluated 15 months after successful arthroscopic rotator cuff repair. Immunoassays were performed with commercially available assay kits to detect the plasma levels of SP.

Statistical analysis were performed with Wilcoxon Sign Rank test. Significance was set at P< 0.05

The concentrations of the neuropeptide SP in sera were measurable in all patients. Patients with postoperative stiffness had statistically significant greater plasma levels of SP than patients in whom arthroscopic repair of rotator cuff tears had resulted in a good outcome (P < 0.05)

Postoperative stiffness (POS) of the shoulder may occur after an apparently successful reconstruction of a rotator cuff tear.

An increased amount of SP in the subacromial bursa has been correlated with the pain caused by rotator cuff disease.

SP stimulates DNA synthesis in fibroblasts, which are the cellular components of the adhesive capsulitis of the shoulder. Also, SP is a pain transmitter peptide, and pain may cause a secondary muscular and/or capsular contracture.

Our results show that the plasma concentrations of substance P in patients with shoulder stiffness after arthroscopic rotator cuff repair are higher compared to plasma levels of SP in patients with a good postoperative outcome.

We cannot determine the cause of POS in our patients, but the findings of this study suggest a possible neuronal role in the pathophysiology of POS after arthroscopic repair of rotator cuff tears. The knowledge of the pathophysiological role of sensory nerve peptides in tissue repair in these patients could open new therapeutic options to manage conditions of the musculo-skeletal system with impaired tissue-nervous system interaction.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 341 - 341
1 May 2010
Franceschi F Longo UG Ruzzini L Rizzello G Maffulli N Denaro V
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Restoring of anatomic footprint may improve the healing and mechanical strength of repaired tendons. A double row of suture anchors increases the tendon-bone contact area, reconstituting a more anatomic configuration of the rotator cuff footprint.

We aimed to investigate if there were differences in clinical and imaging outcome between single row and double row suture anchor technique repairs of rotator cuff tears.

We recruited 60 patients affected by a rotator cuff tear diagnosed on clinical grounds, magnetic resonance imaging evidence of cuff tear and inadequate response to nonoperative management, an unretracted and sufficiently mobile full-thickness rotator cuff lesion to allow a double row repair found at the time of surgery.

In 30 patients, rotator cuff repair was performed with single row suture anchor technique (Group 1). In the other 30 patients, rotator cuff repair was performed with double row suture anchor technique (Group 2). 8 patients (4 in the single row anchor repair group and 4 in the double row anchor repair group) were lost at follow up.

A modified UCLA shoulder rating scale was used to evaluate preoperative and postoperative shoulder pain, function and range of motion, strength and patient satisfaction. All patients received a post-operative MR arthrography at the final follow up appointment.

At the 2 year follow-up, no statistically significant differences were seen with respect to the UCLA score and ROM values. Post-operative MR arthrography at 2 years of follow up in group 1 showed intact tendons in 14 patients, partial thickness defects in 10 patients and full thickness defects in 2 patients. In group 2, MR arthrography showed an intact rotator cuff in 18 patients, partial thickness defects in 7 patients, and full thickness defects in 1 patient.

Biomechanical studies comparing single versus double row suture anchor technique for rotator cuff repair show that a double row of suture anchors increases the tendonbone contact area and restores the anatomic rotator cuff footprint, providing a better environment for tendon healing.

Our study shows that there are no advantages in using a double row suture anchor technique to restore the anatomical footprint. The mechanical advantages evidenced in cadaveric studies do not translate into superior clinical performance when compared with the more traditionally, technically less demanding, and economically more advantageous technique of single row suture anchor repair.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 341 - 341
1 May 2010
Franceschi F Longo UG Ruzzini L Rizzello G Maffulli N Denaro V
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Several studies showed the efficacy of arthroscopic repair for Type II SLAP lesions without other associated lesions, but the only data reported on the association of arthroscopic repair of Type II SLAP lesion and rotator cuff tears involve young and active patient. To our knowledge, no studies have focused on patients over 50.

We evaluated the results of a randomized controlled trial of arthroscopic repair in patients over 50 with rotator cuff tears and Type II SLAP lesion in whom the repair was effected repairing the two lesions, or repairing the rotator cuff tears and performing a tenotomy of the long head of the biceps.

We recruited 63 patients. In 31 patients, we repaired the rotator cuff and the Type II SLAP lesion (Group 1). In the other 32 patients, we repaired the rotator cuff and tenotomized the long head of the biceps (Group 2). 7 patients (2 in the group 1 and 5 in the group 2) were lost to final follow up.

A modified UCLA shoulder rating scale was used to evaluate pre-operative and post-operative shoulder pain, function, active forward flexion, strength and patient satisfaction.

Of 63 patients randomized to one of the two treatments, 5.2 year results were available for 56. 7 patients (2 in the group 1 and 5 in the group 2) did not return at the final follow up.

Statistically significant differences were seen with respect to the UCLA score and ROM values at final follow-up In Group 1 (SLAP repair and rotator cuff repair), the UCLA showed a statistically significant improvement from a pre-operative average rating of 10.4 (range 6 to 14) to an average of 27.9 (24–35) postoperatively (P< 0.001). In Group 2 (biceps tenotomy and rotator cuff repair), the UCLA showed a statistically significant improvement from a pre-operative average rating of 10.1 (range 5 to 14) to an average of 32.1 (range 30 to 35) post-operatively (P< 0.001) There was statistically significant difference in total post-operative UCLA scores and ROM when comparing the two groups post-operatively (P< 0.05).

Arthroscopic management has been recommended for some SLAP lesions, but no studies have focused on patients over 50 with rotator cuff tear and Type II SLAP lesion.

We compared the clinical outcome of patients over 50 affected with rotator cuff tears and Type II SLAP lesion in whom both the defects were repaired, or the rotator cuff tear was repaired and the long head of the biceps tendon was tenotomized. In our hands, the association of rotator cuff repair and biceps tenotomy provides better clinical outcome compared with repair of Type II SLAP lesion and of the rotator cuff.

The repair of the two defects, in fact, can lead to worst clinical results compared with association Rotator cuff repair alone is sufficient to determine a good post-operative outcome, allowing to avoid post-operative stiffness of the shoulder.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 444 - 444
1 Sep 2009
Vadalà G Rainer A Spadaccio C Denaro V Trombetta M
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The use of mesenchymal stem cells (MSCs) for cartilage and bone tissue engineering needs to be supported by scaffolds that may release stimuli for modulate cell activity.

The objective of this study was to asses if MSC undergo differentiation when cultured upon a membrane of nanofibers of poly-L-lactic acid loaded with hydroxyapatite nanoparticles (PLLA/HAp).

The PLLA/HAp nanocomposite was prepared by electrospinning. Membranes microstructure was evaluated by SEM. MSCs were seeded on PLLA/HAp membranes by standard static seeding and cultured either in basal medium or Chondrogenic Differentiation Medium. Cell attachment and engraftment was assessed 3 days after seeding and MSC differentiation was evaluated by immunostaining for CD29, SOX-9 and Aggrecan under a confocal microscope after 14 days.

PLLA/HAp membrane obtained was composed by fibers (average diameter of 7μm) with nano-dispersed hydroxyapatite aggregates (average diameter of 0.3μm). 3 days after seeding, MSCs were well adhered on the PLLA/HAp fibers with a spindled shape. After 14 days of culture all MSCs were positive for SOX-9 in both basal and chondrogenic media groups. Aggrecan was present around the cells. MSCs were either CD29 positive or negative.

We demonstrated that PLLA/HAp nanocomposites are able to induce differentiation of MSCs in chondrocyte-like cells. Since HAp has osteoinductive properties, the chondrogenic phenotype acquired by the MSCs may be either stable or an intermediate stage toward enchondral ossification. The presence of CD29 and SOX-9 double positive cells indicate intermediate differentiation phases.

This nanocomposite could be a susceptible scaffold for bone or cartilage tissue engineering using undifferentiated MSCs.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 6 | Pages 713 - 719
1 Jun 2009
Denaro V Papalia R Denaro L Di Martino A Maffulli N

Cervical spinal disc replacement is used in the management of degenerative cervical disc disease in an attempt to preserve cervical spinal movement and to prevent adjacent disc overload and subsequent degeneration. A large number of patients have undergone cervical spinal disc replacement, but the effectiveness of these implants is still uncertain. In most instances, degenerative change at adjacent levels represents the physiological progression of the natural history of the arthritic disc, and is unrelated to the surgeon. Complications of cervical disc replacement include loss of movement from periprosthetic ankylosis and ossification, neurological deficit, loosening and failure of the device, and worsening of any cervical kyphosis. Strict selection criteria and adherence to scientific evidence are necessary. Only prospective, randomised clinical trials with long-term follow-up will establish any real advantage of cervical spinal disc replacement over fusion.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 271 - 271
1 May 2009
Meloni M Fornasier V Denaro V
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Aims: Free vascularized fibular graft for osteonecrosis of the femoral head is a well established procedure based on the assumption that the graft will provide mechanical support, blood supply to the osteonecrotic head and to introduce mesenchymal stem cells into the affected area of the femoral head.

Methods: We reviewed 25 cases to delineate the pathological features of femoral heads with AVN treated by vascularised fibular grafts which were retrieved at revision surgery when the construct was deemed clinically to have failed.

Results: Review of the patients’ records disclosed that 60.8% were on steroid therapy when the AVN was diagnosed. The recorded time from first symptoms of failure to conversion to total hip arthroplasty was an average of 55 months.

The length of the graft was divided into three zones : zone 3 the femoral neck; zone 2 the lower femoral head or “metaphysis”; zone 1 the more apical or epiphyseal component of the femoral head. The intention was to follow the vascularization of the pedicle and the changes in the three diverse areas of the specimen. The graft showed incorporation with the host bone. In the pedicle there was preservation of vascular patency and tissue viability.

Conclusion: However, this healing process involved a slow reparative resorptive activity which undermined the joint surface. This could suggest that non-resorbable materials in place of tissue grafts can be expected to avoid the negative effect of creeping substitution as an undermining force in the repair and revascularisation of the necrotic area in the head.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 271 - 271
1 May 2009
Franceschi F Longo U Ruzzini L Rizzello G Marinozzi A Denaro V
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Aims: The aim of this study was to analyze the morphological features of the human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears and glenohumeral instability.

Methods: 41 subjects were recruited for the study. 20 subjects (group 1) sustained a rotator cuff tear and proceeded arthroscopic repair of the lesion. 21 subjects (group 2) underwent surgery due to glenohumeral instability. During surgery, under arthroscopic control, a full thickness supraspinatus tendon biopsy was harvested in the middle portion of the tendon. All slices were processed for histological analysis

Results: On surgical specimens of supraspinatus tendon from patients with rotator cuff tears, but not from patients with instability, we found increased preponderance of hyaline degeneration, fibrocartilaginous or chondroid metaplasia, calcification, lipoid degeneration, mucoid or myxoid.

Degenerative changes were more evident on the articular side of the rotator cuff.

Conclusions: The present study provides a description of the histological architecture of human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears. Preexisting degenerative change in the supraspinatus tendon seems to be the main cause of rotator cuff tears.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 272 - 272
1 May 2009
Denaro V Vadalà G Kang J
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Aims: Recent advances in our understanding of intervertebral disc biology have led to develop novel treatments for intervertebral disc degeneration (IDD). With the ability to provide sustained delivery of a potentially therapeutic agent, gene therapy has shown much promise in regard to the treatment of IDD. The aims of this study are (part 1) to test efficacy in delaying course of IDD by intrediscal injection of adenoviral vectors carrying human BMP-2 and (part 2) to describe the application of an inducible system in order to modulate transgene expression.

Methods: (Part 1) IDD was induced in 13 NZW rabbits by anterolateral stab. Three weeks post-stab, saline with or without virus was injected directly into stabbed lumbar discs. Group 1 (n=8) received Ad/hBMP-2 while group 2 (n=5) received saline only. Rabbits were followed longitudinally with MRIs and X-rays preoperatively for up to 12 weeks post-stab. ELISAs were done to confirm BMP-2 production. (Part 2) Human nucleus pulposus cells (NPC) were transduced with an adenoviral vector that expresses GFP under the control of a tetracycline (Ad/GFPtet). Cells were cultutred with and without tetracycline. Transgene expression was assessed by detecting GFP signal with both the FACS and the fluorescent microscope.

Results: (Part 1) By 12 weeks, the saline-injected discs had lost 49% of their MRI Index, in contrast to only a 25% decrease for the Ad/hBMP-2 treated discs. X-rays demonstrated no obvious bony intervertebral fusion in either group. ELISAs confirmed vigorous hBMP-2 production 3 weeks after therapeutic gene transfer. (Part 2) NPC expressed GFP after transduction. GFP positivity was not observed two days after administration of tetracycline. The cells expressed GFP again three days after removal of tetracycline.

Discussion: The results of this study demonstrate the efficacy of vector-mediated BMP-2 gene transfer to alter the course of IDD in a reproducible animal model, as well as the potential to control transgene expression, improving safety.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 275 - 275
1 May 2009
Franceschi F Longo U Ruzzini L Rizzello G Marinozzi A Denaro V
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Aims: We reviewed our experience to determine the results of arthroscopic repair in patients over 50 with rotator cuff tears and Type II SLAP lesion in whom the repair was effected repairing the two lesions, or repairing the rotator cuff tears and performing a tenotomy of the long head of the biceps.

Methods: We recruited 121 patients older than 50 years in whom a symptomatic rotator cuff tear had failed non-surgical management and was affecting daily activities.

We assigned them retrospectively to one of the two groups: Group 1 underwent arthroscopic repair of the rotator cuff and repair of the type II SLAP lesion. Group 2 underwent arthoscopic repair of the rotator cuff tear and a tenotomy of the long head of the biceps.

Results: There was statistically significant difference in total postoperative UCLA scores and ROM when comparing the two groups postoperatively (P< 0.05).

Conclusions: We compared the clinical outcome of patients over 50 affected by the association of rotator cuff tears and Type II SLAP lesion, in whom both the defects were repaired, or the rotator cuff tear was repaired and the long head of the biceps tendon was tenotomized. In our hands, the association of rotator cuff repair and biceps tenotomy provides better clinical outcome compared with the association of Type II SLAP lesion repair and rotator cuff repair at three years of follow-up.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 8 | Pages 995 - 999
1 Aug 2008
Longo UG King JB Denaro V Maffulli N

There is a trend towards the use of double-bundle techniques for the reconstruction of the anterior cruciate ligament. This has not been substantiated scientifically. The functional outcome of these techniques is equivalent to that of single-bundle methods. The main advantage of a double-bundle rather than a single-bundle reconstruction should be a better rotational stability, but the validity and accuracy of systems for the measurement of rotational stability have not been confirmed.

Despite the enthusiasm of surgeons for the double-bundle technique, reconstruction with a single-bundle should remain the standard method for managing deficiency of the anterior cruciate ligament until strong evidence in favour of the use of the double-bundle method is available.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1525 - 1526
1 Nov 2007
Franceschi F Longo UG Ruzzini L Denaro V

Among the variety of differential diagnoses for chronic patellar tendinopathy, isolated tuberculosis is extremely rare. We report such a case, without any evident primary contiguous or distant focus, in a 31-year-old immunocompetent male.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 152 - 152
1 Mar 2006
Denaro V Vadala G Sobajima S Kang J Gilbertson L
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Introduction: Current therapies for degenerative disc disease (DDD) are aimed at treating the pathologic and disabling conditions arising from DDD rather than directly treating the underlying problem of disc degeneration. Our group are exploring the potential of Cell Therapy to repopulate the disc and stopping the progressive loss of proteoglycans. Stem cells appear to be excellent candidates for this purpose, based on their ability to differentiate along multiple connective tissue lineages. The purpose of this study is to investigate the in-vitro interaction between muscle-deroved stem cells (MdSC) and nucleus polposus cells (NPCs) and to determine in-vivo viability of mesenchymal stem cell (MSC) in the harsh environment of the IVD

Materials and Methods: (1) Human NPCs were isolated from patients undergoing disc surgery and were co-cultured for 2 weeks with MdSCs from 3-wk-old mdx mice and in monolayer culture system at different ratios of 0:100, 25:75, 50:50, 75:25, 100:0. Proteoglycan synthesis and DNA content were measured. (2) Rabbit mesenchymal stem cells were isolated from bone marrow and tagged with a retrovirus delivered LacZ reporter gene for tracking. MSCs were then injected into a healthy rabbit IVD via 30G needle. Rabbits were sacrificed at postoperatively at 3, 6, 12 and 24 weeks. Histological analysis for MSC viability was performed.

Results: (1) Co-culturing of NPCs with MdSCs in the monolayer culture system resulted in vigorous increases in proteoglycans synthesis as compared with NPCs alone. The increases were on the 200% for an NPC-to-MDSC ratio of 75:25. DNA content also increased with co-culture. (2) Histological examination revealed presence of MSCs expressing LacZ without apparent decrease in numbers or diminishment of protein production.

Conclusion: The data from this study show that there is a synergistic effect between stem cells and nucleus pulposus cells resulting in upregulated proteoglycan synthesis in-vitro. Mesenchymal stem cells remain viable and continue to express an ex vivo transduced protein without appreciable cell loss for up to 24 weeks post transplantation into the rabbit IVD. These results suggest that MSCs can survive in the harsh environment of the IVD and may favourably modify ECM production. These studies support the feasibility of developing a stem cell therapy approach for DDD.