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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 119 - 119
1 Dec 2020
Giacomo GD Ambrosio L Cicione C Tilotta V Papalia R Vadalà G Denaro V
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In the last decade, skeletal muscle has been recognized as an endocrine organ able to release molecules that may act as paracrine or endocrine factors, namely myokines. Among these, irisin is secreted upon muscle contraction after physical exercise (PE) and has been demonstrated to yield anabolic effects on different cell types. Recently, irisin has been shown to improve cortical bone mass, geometry and strength, hence resembling the effect of PE. It has also been reported that irisin levels in the serum and synovial fluid of patients with knee osteoarthritis (OA) were negatively correlated with OA severity. Therefore, we hypothesized that irisin may improve cartilage metabolism and blunt the osteoarthritic process.

Human osteoarthritic chondrocytes (hOAC) were isolated from osteochondral specimens of patients undergoing total knee joint replacement. After in vitro expansion, hOAC were put in a three-dimensional culture system (alginate beads) and treated with either phosphate-buffered saline (control) or irisin (25 ng/mL). After 1 week, the amount of glycosaminoglycans (GAG) was evaluated using dimethylmethylene blue (DMMB) and PicoGreen assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 gene expression levels.

hOAC treated with irisin showed a significant higher GAG content compared to the control group (p < 0.01). Moreover, irisin was able to reduce the expression of catabolic (MMP-1, -13, iNOS) and pro-inflammatory (IL-1, IL-6) markers, while incrementing the expression of TIMP-1 and -3 (p < 0.001).

Our results showed that irisin was able to stimulate GAG synthesis and diminish extracellular matrix catabolism in hOAC, demonstrating the existence of a cross-talk between cartilage and muscle possibly supporting the beneficial role of PE on cartilage homeostasis.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 94 - 94
1 Dec 2020
Ambrosio L Vadalà G Cattani C Bernardini R Giacalone A Papalia R Denaro V
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Cartilage neoangiogenesis holds a key role in the development of osteoarthritis (OA) by promoting cartilage degradation with proteoglycan loss, subchondral bone sclerosis, osteophyte formation and synovial hyperplasia. This study aimed to assess the in vivo efficacy of bevacizumab, an antibody against vascular endothelial growth factor (VEGF) in an OA animal model.

24 New Zealand white rabbits underwent anterior cruciate ligament transection in order to spontaneously develop knee OA. Animals were divided into four groups: one receiving a sham intraarticular knee injection (saline) and three groups treated with 5, 10, and 20 mg intraarticular bevacizumab injections. The biological effect of the antibody on cartilage and synovium was evaluated through histology and quantified with the Osteoarthritis Research Society International (OARSI) scores. Immunohistochemical analysis was conducted to investigate type 2 collagen, aggrecan, and matrix metalloproteinase 13 (MMP-13) expression in both cartilage and synovium.

Intraarticular bevacizumab led to a significant reduction of cartilage degeneration and synovial OA alterations. Immunohistochemistry showed a significantly reduced MMP-13 expression in all experimental groups, with the one receiving 20 mg bevacizumab showing the lowest. Furthermore, the antibody showed to increment the production of aggrecan and type 2 collagen after administration of 5, 10, and 20 mg. The group treated with 20 mg showed the highest levels of type 2 collagen expression, while aggrecan content was even higher than in the healthy cartilage.

Intraarticular bevacizumab has demonstrated to effectively arrest OA progression in our model, with 20 mg being the most efficacious dose. By inhibiting cartilage and synovial neoangiogenesis, bevacizumab may serve as a possible disease-modifying osteoarthritis drug (DMOAD) in the next future.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 47 - 47
1 Dec 2020
Cicione C Papalia R Di Giacomo G Tilotta V Ambrosio L Russo F Vadalà G Denaro V
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Anterior cruciate ligament injury is the most common and economically costly sport injuries, frequently requiring expensive surgery and rehabilitation. Post-operative knee septic arthritis represents a serious complication with an incidence rate between 0.14% and 1.7%. A common practice to avoid septic arthritis is the “vancomycin wrap”, consisting in the soaking of the graft for 10–15 minutes within a sterile gauze swab previously saturated with 5 mg/mL vancomycin. Even though several studies have been conducted to investigate vancomycin toxicity on different musculoskeletal tissues or cells, little is known about the effect of such antimicrobial on tendon-derived cells.

The aim of this study was to determine the in vitro toxicity of different concentrations of vancomycin at different time points on human primary tenocytes (hTCs).

hTCs were isolated from hamstring grafts of patients undergoing anterior cruciate ligament reconstruction. After expansion, cells were treated with different concentrations of vancomycin (2.5, 5, 10, 25, 50 and 100 mg/mL) for 10, 15, 30 and 60 minutes. In vitro toxicity was evaluated measuring: metabolic activity through the reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT Assay); cytotoxicity (Live/Dead assay); and cell apoptosis (Annexin V apoptosis kit).

The metabolic activity of hTCs was affected by vancomycin treatment starting from 10 mg/mL at all time points (p < 0.05) and dropped down at 100 mg/mL at all time points (0.05 < p < 0.001). Cells viability resulted to be unaffected only by 2.5 mg/mL vancomycin at all time points. Vancomycin resulted to be cytotoxic starting from 10 mg/mL after 15 minutes of treatment and at all higher concentrations under study at all time points. Cells died when treated with vancomycin concentrations higher than 5 mg/mL but not through apoptosis, as confirmed by negative staining for Annexin V.

In our experimental conditions, vancomycin resulted to be toxic on hTCs at concentrations higher than 5 mg/mL. The use of this antibiotic on tendons to prevent infections could be useful and safe for resident cells if used at a concentration of 2.5 mg/mL up to 1 hour of treatment.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 90 - 90
1 Dec 2020
Gori M Giannitelli SM Papalia R Vadalà G Denaro V
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Invasive intraneural electrodes implanted in peripheral nerves are neural prosthetic devices that are exploied to control advanced neural-interfaced prostheses in human amputees. One of the main issues to be faced in chronic implants is represented by the gradual loss of functionality of such intraneural interfaces due to an electrical impedance increase caused by the progressive formation of a fibrotic capsule around the electrodes, which is originally due to a nonspecific inflammatory response called foreign body reaction (FBR).

In this in vitro work, we tested the biocompatibility and ultra-low fouling features of the synthetic coating - poly(ethylene glycol) (PEG) - compared to the organic polymer - zwitterionic sulfated poly(sulfobetaine methacrylate) (SBMA) hydrogel - to prevent or reduce the first steps of the FBR: plasma protein adsorption and cell adhesion to the interface.

Synthesis and characterization of the SBMA hydrogel was done. Preliminary biocompatibility analysis of the zwitterionic hydrogel, using hydrogel-conditioned medium, showed no cytotoxicity at all vs. control. We seeded GFP-labelled human myofibroblasts on PEG- and SBMA hydrogel-coated polyimide surfaces and evaluated their adhesion and cell viability at different time-points. Because of the high hydration, low stiffness reflecting the one of neural tissue, and ultra-low fouling characteristics of the SBMA hydrogel, this polymer showed lower myofibroblast adhesion and different cell morphology compared to adhesion controls, thereby representing a better coating than PEG for potentially mitigating the FBR.

We conclude that soft SBMA hydrogels could outperform PEG coatings in vitro as more suitable dressings of intraneural electrodes. Furthermore, such SBMA-based antifouling materials can be envisioned as long-term diffusion-based delivery systems for controlled release of anti-inflammatory and anti-fibrotic drugs in vivo.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 95 - 95
1 Dec 2020
Russo F Ambrosio L Peroglio M Wangler S Guo W Grad S Alini M Vadalà G Papalia R Denaro V
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The use of stem cells transplanted into the intervertebral disc (IVD) is a promising regenerative approach to treat intervertebral disc degeneration (IDD). The aim of this study was to assess the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) loaded with human mesenchymal stem cells (hMSCs), on IVD extracellular matrix synthesis and nucleus pulposus (NP) marker expression in a whole IVD culture model.

HA was blended with batroxobin (BTX), a gelling agent activated in presence of PRP to construct a hydrogel. Bovine IVDs (n=25) were nucleotomised and filled with 1×106 or 2×106 hMSCs suspended in ∼150 mL of the PRP/HA/BTX hydrogel. IVDs harvested at day 0 and nucleotomised IVDs with no hMSCs and/or hydrogel were used as controls. hMSCs alone or encapsulated in the hydrogel were also cultured in well plates to examine the effect of the IVD microenvironment on hMSCs. After 1 week, tissue structure, scaffold integration and gene expression of anabolic (collagen type I, collagen type II and aggrecan), catabolic (matrix metalloproteinase 3 – MMP-3 –, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motifs 4) and NP cell (cytokeratin 19, carbonic anhydrase 12, cluster of differentiation 24) markers were assessed.

Histological analysis showed a good integration of the scaffold within the NP area with cell repopulation. At the gene expression level, the hMSC-loaded hydrogels demonstrated to increase disc cell anabolic and catabolic marker expression and promoted hMSC differentiation towards a NP cell phenotype.

This study demonstrated that the HA/PRP/BTX may represent a valid carrier for hMSCs being capable of stimulating cell activity and NP marker expression as well as achieving a good integration with the surrounding tissues.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 18 - 18
1 Apr 2017
Russo F Musumeci M De Strobel F Bernardini M De Benedictis G Denaro L D'Avella D Giordano R Denaro V
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Background

Stem cell based intervertebral disc (IVD) regeneration is quickly moving towards clinical applications. However, many aspects need to be investigated to routinely translate this therapy to clinical applications, in particular, the most efficient way to deliver cell to the IVD. Cells are commonly delivered to the IVD through the annulus fibrosus (AF) injection. However, recent studies have shown serious drawbacks of this approach. As an alternative we have described and tested a new surgical approach to the IVD via the endplate-pedicles (transpedicular approach). The Purpose of the study was to test MSCs/hydrogel transplantation for IVD regeneration in a grade IV preclinical model of IDD on large size animals via the transpeducular approach with cell dose escalation.

Methods

Adult sheep (n=18) underwent bone marrow aspiration for autologous MSC isolation and expansion. MSC were suspended in autologous PRP and conjugated with Hyaluronic Acid and Batroxobin at the time of transplant (MSCs/hydrogel). Nucleotomy was performed via the transpedicular approach in four lumbar IVDs and that were injected with 1) hydrogel, 2) Low doses of MSC/hydrogel, 3) High doses of MSC/hydrogel, 4) no injection (CTRL). The endplate tunnel was sealed using a polyurethane scaffold. X-ray and MRI were performed at baseline and 1,3,6,12 months. Disc macro- and micro-morphology were analysed at each time point.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_9 | Pages 109 - 109
1 May 2016
Papapietro N Di Martino A Marinozzi A Cancilleri F Denaro V
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Introduction

One of the major concerns in the use of modular hip prostheses is the structural failure of one or more components of the prosthesis, with total mechanical failure. In literature there are sporadic cases of breakage of the prosthetic neck in patients with high functional demand.

Material and methods

In our experience we have implanted a model of modular hip prostheses in 38 patients. In 17 of these patients it was implanted a neck made of titanium alloy, while in the remaining 21 was utilised a CrCo neck. In 5 of the 17 patients with neck titanium it has been a spontaneous rupture of the neck in a time ranging from 12 to 24 months. We proceeded with the replacement of the titanium neck with similar neck made of CrCo alloy in 5 patients with failed neck, and we decided to call the remaining 12 patients with titanium neck, offering them the revision of the system. All patients accepted the revision surgery.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 171 - 171
1 Jul 2014
Papalia R Vadalà G Franceschi F Franceschetti E Zampogna B Maffulli N Denaro V
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Introduction

Rotator cuff healing after an arthroscopic repair is discussible because of the high incidence of failures. Among biologic augmentations currently used, platelet-rich plasma (PRP) is one of the most applied, supposed to enhance and accelerate the healing process in different musculoskeletal disorders. However, the evidence supporting its successful administration is still lacking, especially in the field of the rotator cuff repair. Our purpose is to clarify if the recovery is accelerated and the integrity of repaired construct is increased in patients undergoing PRP injections after arthroscopic repair of the rotator cuff.

Patients & Methods

Thirty-eight patients with full-thickness rotator cuff tears have been enrolled after they had been informed about the use of PRP and the timing of its application postoperatively. Seventeen patients underwent arthroscopic rotator cuff repair and PRP injections (3 injections at 10 days each other), 21 underwent arthroscopic rotator cuff repair without PRP injections. Outcomes were assessed preoperatively, at 3, 6, 12, and minimum 16 months after surgery (average 17.7 +/− 1.7 months). Constant system, the University of California at Los Angeles (UCLA) system and a Visual Analogue Scale (VAS) scale were used; range of motion and strength in all planes were also assessed. The healing of the repair was assessed at magnetic resonance imaging at a minimum follow up of 6 months from surgery. All patients had the same rehabilitation protocol.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 173 - 173
1 Jul 2014
Papalia R Vadalà G Moro L Franceschi F Vasta S Albo E Tecame A Maffulli N Denaro V
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Introduction

recent studies recognised metabolic abnormalities as additional factors in the development of rotator cuff (RC) tendinopathy. It has been hypothesised that the insertional area of this tendon is susceptible to degenerative changes due to intrinsic hypovascularization. The mechanisms underlying this process are not yet clear. In this study we attempted to confirm if larger lesions of the RC are related to impaired vasodilatatory response of the local circulation in conditions of “hemodynamic stress”.

Patients & Methods

it was assumed that impaired vasal reaction to “hemodynamic stress” was a systemic condition. This phenomenon should therefore be not limited to the critical area of the tendon tear. Given this assumption post-ischemic vasodilation of brachial artery was studied through an echo-doppler (US) evaluation. 50 patients (mean 61 ± 4, range 50–65) all scheduled for surgical rotator cuff repair following a tendon tear, were enrolled. Three preoperative measurements of the brachial artery diameter before and after application of an ischemic band were collected. The size of the lesions was later assessed at the time of surgery. A statistical analysis was carried on to investigate the correlation between US assessment of brachial artery diameter and the corresponding size of the RC lesions. UCLA and ASES scores were also measured to assess clinical and functional outcomes.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 306 - 306
1 Jul 2014
Vadalà G Russo F Pattappa G Peroglio M Grad S Stadelmann V Alini M Denaro V
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Summary Statement

To test regenerative therapies for the intervertebral disc it is necessary to create a cavity in the nucleus polposus mantaining the annulus fibrosus intact. The transpedicular mechanical nucleotomy represents the best method for this purpose.

Introduction

New cells/hydrogel based treatments for intervertebral disc (IVD) regeneration need to be tested on animal models before clinical translation. Ovine IVD represents a good model but doesn't allow the injection of a significant volume into intact IVD.

The objective of the study was to compare different methods to create a cavity into ovine nucleus pulposus (NP) by enzymatic digestion (E), mechanical discectomy (M) and a combination of both (E+M), as a model to study IVD regeneration strategies with intact anulus fibrosus (AF).


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 124 - 124
1 Jul 2014
Papalia R Vadala G Franceschi F Balzani LD Zampogna B D'Adamio S Maffulli N Denaro V
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Introduction

Ostochondral lesion of the knee is a common cause of chronic knee pain. Arthroscopic treatment with subcondral microfracture is a widespread technique leading to noticeable improvement of knee function and pain. To improve the effectiveness of this treatment options, we thought to add intra (PRF) or post-operative (PRP) growth factors. Platelet rich plasma (PRP) is obtained by centrifugation of the blood to produce a plasma with high concentration of platelets and growth factors. This latter represents a promising method to manage degenerative cartilage lesion and can be used postoperatively to improve clinical results of patients treated arthroscopically. Platelet Rich Fibrin (PRF) has been presented as a second-generation platelet concentrate, and it is used intraoperatively to cover the microfracuteres’ holes. No literature was found about using of PRF intraoperative in association with arthroscopic microfracture technique. The aim of this study is to compare clinical outcomes of the treatment of knee osteochondral lesion using arthroscopic microfracture technique alone or in association with PRF Intraoperative application using “Vivostat” system or with PRP “ReGen Lab” postoperative injection.

Patients & Methods

90 patients with clinical and radiographic evidence of osteochondral lesion of the medial or lateral compartment of the knee were enrolled. All patients received arthroscopic debridement and Microfractures and were randomised into 3 groups: 30 patients received microfractures and intraoperative PRF “Vivostat” injection(Group A), 30 patients received microfracture and 3 intra-articular injections of 5.5 mL PRP “Regen”(Group B), 30 patients received microfracture only. IKDC, KOOS and VAS score were administered to all patients before starting the treatment, at 1, 6 and 12 months from the end of the management.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 340 - 340
1 Jul 2014
Vadalà G Musumeci M Giacalone A Russo F Denaro V
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Summary Statement

Intra-articular injection of humanised monoclonal anti-VEGF antibody (Bevacizumab, Avastin®) in a osteoarthritis rabbit model is related to positive restorative effects in terms of histopathologic evaluation.

Introduction

Vascular endothelial growth factor (VEGF) is generally undetectable in adult human articular cartilage under physiological conditions. Upon exposure to pathological stimulation such as inflammation, hypoxia or accumulating mechanical stress, VEGF would be up regulated in hypertrophic chondrocytes of arthritic cartilage leading to osteophyte formation, disregulation of chondrocyte apoptosis and induction of catabolic factors, including matrix metalloproteinases (MMPs). This in vivo study aims to investigate the potential role of VEGF inhibition to treat Osteoarthritis (OA), through intra-articular injection of Bevacizumab, a humanised monoclonal anti-VEGF antibody, in a OA rabbit model.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 9 - 9
1 Jan 2011
Maffulli N Walley G Sayana M Longo U Denaro V
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To evaluate the effects of eccentric strengthening exercises (ESE) in athletic patients with Achilles tendinopathy. Forty five athletic patients (29 men, average age 26 years; 16 women, average age 28 years; average height: 173 ± 16.8, range 158 to 191; average weight 70.8 kg ± 15.3, range 51.4 to 100.5) with clinical diagnosis of unilateral tendinopathy of the main body of the Achilles tendon completed the VISA-A questionnaire at first attendance and at their subsequent visits. The patients underwent a graded progressive eccentric calf strengthening exercises programme for 12 weeks.

The mean pre-management VISA-A scores of 36 (SD 23.8; 95% C.I.: 29 – 46) improved to 52 (SD 27.5; 95% C.I.: 41.3 – 59.8) at the latest follow up (p = 0.001). Twenty seven of the 45 patients responded to the eccentric exercises. Of the 18 patients who did not improve with eccentric exercises, 5 (mean age: 33 years) improved with two peritendinous aprotinin and local anaesthetic injections. 10 of the 18 patients (9 men, mean age 35 years; 1 woman aged 40 years) who did not improve with eccentric exercises and aprotinin injections proceeded to have surgery. The remaining three patients (3 women, mean age 59.6 years; 2 men, mean age 63 years) of the 18 non-responders to eccentric exercises and aprotinin injections declined surgical intervention.

ESE in athletic patients provide comparable clinical outcome compared to our previous results in non-athletic patients. ESE are a viable option for the management of AT in athletes, but, in our hands, only around 60% of our athletic patients benefited from an intensive, heavy load eccentric heel drop exercise regimen alone. If ESE fail to improve the symptoms, aprotinin and local anaesthetic injections should be considered. Surgery is indicated in recalcitrant cases after 3 to 6 months of non operative management.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 43 - 43
1 Jan 2011
Maffulli N Franceschi F Longo U Ruzzini L Battistoni F Denaro V Battistoni F Walley G Dicuonzo G
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Our objective was to determine the plasma levels of substance P (SP) in patients with postoperative stiffness 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.

The mean plasma levels of SP in patients with postoperative stiffness were significantly greater than those in the control group (81.06 ± 27.76 versus 23.49 ± 5.64, P < 0.05).

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. The neuronal upregulation of SP shown in the plasma of patients with post operative shoulder stiffness may underlay not only the symptoms of adhesive capsulitis, but also its development.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 42 - 43
1 Jan 2011
Maffulli N Franceschi F Longo U Ruzzini L Rizzello G Denaro V
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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. Our hypothesis was that there was no difference in clinical outcome between repairing of the Type II SLAP lesion and tenotomy of the long head of the biceps tendon after having repaired the rotator cuff tear. This was a randomized controlled clinical trial.

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 tenomized 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.

At the 5.2 year follow-up, statistically significant differences were seen with respect to the UCLA score and ROM values. 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).

There are no advantages in repairing a Type II SLAP lesion when associated with a rotator cuff tear in patients over 50. Rotator cuff repair alone is sufficient to produce a good post-operative outcome, allowing to avoid post-operative stiffness of the shoulder.


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.


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.