Roberto Giardino

Publications of Roberto Giardino

• EARLY TERM EFFECT OF ADULT CHONDROCYTE TRANSPLANTATION IN AN OSTEOARTHRITIS ANIMAL MODEL.

  Authors: Giovanna Desando, Carola Cavallo, Matilde Tschon, Gianluca Giavaresi, Lucia Martini, Milena Fini, Roberto Giardino, Andrea Facchini, Brunella Grigolo

  Tissue engineering. Part A. 03/2012;

  Abstract In this study, we investigated the efficacy of the transplantation of autologous articular chondrocytes seeded onto a hyaluronan based scaffold, known as Hyaff®-11, on the treatment of earlyAbstract In this study, we investigated the efficacy of the transplantation of autologous articular chondrocytes seeded onto a hyaluronan based scaffold, known as Hyaff®-11, on the treatment of early cartilage lesions in a rabbit osteoarthritis (OA) model. The hypothesis of the study was that this treatment could enhance cartilage repair after OA induction. OA was induced surgically by Anterior Cruciate Ligament Transection (ACLT) in thirty rabbits. Animals were divided in three groups, according to treatment: group 1:ACLT; group 2: Chondrocytes+Hyaff®-11; group 3: Hyaff®-11 alone. Animals were euthanized respectively at 3 and 6 months after the treatment. Histomorphometrical analyses were performed by means of FI, CT and SBT evaluations. Histological appearance was scored according to Modified Kraus' Mankin and OARSI scores. Immunohistochemical analyses were carried out for type I and II collagens, MMP-1 and MMP-3. Comparison between groups and follow-up for each outcome was performed with general linear model with Sidak correction. Histomorphometrical evaluations at 3 and 6 months demonstrated that OA lesions significantly worse followed by Hyaff®-11 treatment, whereas Chondrocytes+ Hyaff®-11 treatment had the best overall subjective grade. Overall raw histological scores demonstrated a significant improvement with chondro-HA treatment at 3 months compared to HA in cartilage repair processes. Immunohistochemical analyses displayed a strong positivity for type II collagen in Chondrocytes+ Hyaff®-11group from 3 months compared to HA group. No staining was observed in MMP-3 expression in this group at any experimental point. The use of Chondrocytes+ Hyaff®-11 for the treatment of early OA lesions produced, already at 3 months, a repair tissue showing better macroscopic, histological and immunohistochemical results than those observed after Hyaff®-11 treatment. Thus, the transplantation of Chondrocytes+ Hyaff®-11 would seem to be advocated in the very early stage of the OA disease when a precocious action is mandatory.

• New PMMA-based composites for preparing spacer devices in prosthetic infections.

  Authors: Gianluca Giavaresi, Elisa Bertazzoni Minelli, Maria Sartori, Anna Benini, Annapaola Parrilli, Maria Cristina Maltarello, Francesca Salamanna, Paola Torricelli, Roberto Giardino, Milena Fini

  Journal of materials science. Materials in medicine. 02/2012;

  Even though the systemic antibiotic therapy is usually applied after prosthetic infections surgical treatments, it is unable to reach the infection site in sufficient concentrations to eradicateEven though the systemic antibiotic therapy is usually applied after prosthetic infections surgical treatments, it is unable to reach the infection site in sufficient concentrations to eradicate bacteria. Delivering antibiotics locally with the use of custom made device (spacer or nail coating) might eradicate or reduce the infection and the risk of recolonization, providing a very high concentration of antibiotic. PMMA-based (Mendec Spine(®)) composites with BaSO(4) were enriched with β-tricalcium phosphate (Porosectan-TCP) or only a slightly higher BaSO(4) concentration (Porosectan-BaSO(4)) to obtain higher porosity. The aim of the study was to evaluate: (i) drug absorption capability and drug release kinetics in vitro soaking them with a combined solution of gentamicin and vancomycin, (ii) their in vitro and in vivo biocompatibility, and finally, (iii) they were tested preliminarily in an experimental model of bone infection. The simultaneous presence of β-TCP and BaSO(4) resulted in the formation of a texture of interconnecting channels with different diameters, from a few microns to several hundred microns, which totally filled the material. The porosity, determined by microcomputed tomography, was significantly higher in both tested plain composites (Porosectan-TCP: +17.3%; Porosectan-BaSO(4): +7.5%) in comparison to control composite material (Mendec Spine(®)). The kinetics of antibiotic release from composites was rapid and complete, producing high drug concentrations for a short period of time. Both composites showed a good level of biocompatibility. The osteomyelitic model confirmed that both composites, soaked in antibiotic solution, were able to cure bone infection. These composites could be useful for preparing devices for prosthetic joint infections treatment also allowing the use of antibiotics solution at required concentrations.

• In vivo preclinical evaluation of the influence of osteoporosis on the anchorage of different pedicle screw designs.

  Authors: Gianluca Giavaresi, Milena Fini, Roberto Giardino, Francesca Salamanna, Maria Sartori, Veronica Borsari, Silvia Spriano, Chiara M Bellini, Marco Brayda-Bruno

  European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 05/2011; 20(8):1289-96.

  We investigate the anchorage of pedicle screws with different surface treatments in osteoporotic bone. Eight ewes were divided into two groups of four animals each: four sheep underwent bilateralWe investigate the anchorage of pedicle screws with different surface treatments in osteoporotic bone. Eight ewes were divided into two groups of four animals each: four sheep underwent bilateral ovariectomy (OVX Group), whereas the operation was simulated in the remaining group (SHAM Group). Eighteen months after the first operation, the Dynesys(®) System was fitted to the sheep using pedicle screws with three different surface treatments: untreated, rough blasted (uncoated) and bioactive coated (bioactive). Uncoated screws showed a significantly higher bone ingrowth value compared with the untreated screws in the OVX group (9.3%, p < 0.005) and a significantly lower bone ingrowth value in the SHAM group (-11.0%, p < 0.05). Furthermore, the bioactive pedicle screws had a significant lower bone ingrowth value than the untreated screws in the SHAM group (-12.1%, p < 0.05). These results suggest that both tested surface treatments of pedicular screws may provide an advantage in terms of bone quality and osseointegration, when implanted in osteoporotic vertebrae.

• Pietro Loreta and his contribution to surgery in the 19th century.

  Authors: Nicolò Nicoli Aldini, Milena Fini, Roberto Giardino

  The American surgeon. 03/2011; 77(3):290-6.

  Pietro Loreta (1831 to 1889), head of surgery at the University of Bologna, Italy, is at present a little-known name. However, in the field of surgery in the second half of the 19th century, hisPietro Loreta (1831 to 1889), head of surgery at the University of Bologna, Italy, is at present a little-known name. However, in the field of surgery in the second half of the 19th century, his contributions to various areas, especially that of bladder stone treatment and gastric surgery, aroused great interest also at the international level. This survey focuses on both of these subjects that are particularly indicative of Loreta's activity. While he was trying to improve the operation of perineal cystotomy, which was about to be abandoned, he was faced with the new frontier of gastrointestinal tract surgery. Surgery was in rapid transformation, and the practice of a general surgeon still encompassed the domains of different surgical specialties, which would develop individually afterward. Loreta was a pupil of the outstanding surgeon Francesco Rizzoli and some of his pupils such as Alessandro Codivilla and Bartolo Nigrisoli became heads of surgery. His attitude of caution, that he recommended in his writings, is more remarkable considering his problematic nature and might be the most significant and original trait of Loreta's personality.

• Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses.

  Authors: Paola Torricelli, Milena Fini, Giuseppe Filardo, Matilde Tschon, Mario Pischedda, Alessandra Pacorini, Elizaveta Kon, Roberto Giardino

  International orthopaedics. 03/2011; 35(10):1569-76.

  Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving theTissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to other therapies. After ultrasonographic localisation of the lesion, the autologous BMMNC suspension and PRP were injected directly into the core lesion. BMMNC and platelet count as well as growth factors in PRP were measured to determine factors influencing the clinical outcome. Horses showed a marked improvement in their degree of lameness and 84.6% were able to return to competition. Among all the factors studied, the platelet concentration predicted the healing time: significantly faster recovery (p = 0.049) was observed in cases of PRP with more than 750 × 10(3)/μl platelets. Competition horses are involved in highly demanding activities, thus being a similar model for the high mechanical overload typical of human athletes. The promising results obtained suggest that this combined biological approach may be useful even for the treatment of recalcitrant overuse musculoskeletal injuries in highly demanding patients if the appropriate dose of cells and GFs is applied.

• Lights and shadows concerning platelet products for musculoskeletal regeneration.

  Authors: Matilde Tschon, Milena Fini, Roberto Giardino, Giuseppe Filardo, Dante Dallari, Paola Torricelli, Lucia Martini, Gianluca Giavaresi, Elizaveta Kon, Maria Cristina Maltarello, Andrea Nicolini, Angelo Carpi

  Frontiers in bioscience (Elite edition). 01/2011; 3:96-107.

  Various types of platelet (PLT) products, such as Platelet Rich Plasma (PRP) and Platelet Gel (PG), derived from autologous peripheral blood, have been used for tissue repair. The good clinicalVarious types of platelet (PLT) products, such as Platelet Rich Plasma (PRP) and Platelet Gel (PG), derived from autologous peripheral blood, have been used for tissue repair. The good clinical outcomes, due mainly to their safety and Growth Factor (GF) content, have led to a wide use of PLT products in many fields of medicine. However, until now the existing literature adds controversies to the use of PLT concentrates. When talking about PLTs and their products, a great number of variables have to be considered. These variables are mainly related to PRP preparation methods, the type of activators, intra- and inter-species variability, types of pathology to be treated, the ways and times of administration and the association of PRP or PG with other treatments. This review considers and discusses these causes of variability with particular attention to orthopaedic implications. The possibility of improving the knowledge on variables affecting therapeutic efficacy will surely help in addressing the best combination of factors implied in the different steps of PLT concentrate preparation and use.

• Nuclear phospholipase C in biological control and cancer.

  Authors: Giulia Ramazzotti, Irene Faenza, Matilde Y Follo, Roberta Fiume, Manuela Piazzi, Roberto Giardino, Milena Fini, Lucio Cocco

  Critical reviews in eukaryotic gene expression. 01/2011; 21(3):291-301.

  Inositol lipids are key regulators of several cellular functions. The identification of an independent nuclear polyphosphoinositides signaling machinery has led the way to find new roles for theseInositol lipids are key regulators of several cellular functions. The identification of an independent nuclear polyphosphoinositides signaling machinery has led the way to find new roles for these molecules. PI-PLC-β1 is the most extensively studied PLC isoform in the nuclear compartment and a key player in the regulation of nuclear lipid signaling. Nuclear PI-PLC-β1 is involved in cell cycle progression and differentiation in response to growth factor stimulation. A growing body of evidence has demonstrated that nuclear phosphoinositides are also involved in cancer cell generation, proliferation, and resistance to apoptosis. Evidence on ex vivo human cancer cells from patients with myelodysplastic syndromes (MDS) confirmed these observations, suggesting the involvement of PI-PLC-β1 both in the pathogenesis of the disease and in the progression of MDS to acute myeloid leukemia. These studies have offered new targets for the development of novel therapeutic strategies as well as new prognostic tools.

• Inter-penetrating hydrogels (IPHs) as a new class of injectable polysaccharide hydrogels with thixotropic nature and interesting mechanical and biological properties

  Authors: Rolando Barbucci, Roberto Giardino, Milena De Cagna, Lucia Golini, Daniela Pasqui

  Soft Matter. 01/2010; 6:3524-3532.

  Hydrogels are important and very promising materials for biomedical applications, such as cell scaffolds and drug delivery systems. A new class of injectable materials was obtained by mixingHydrogels are important and very promising materials for biomedical applications, such as cell scaffolds and drug delivery systems. A new class of injectable materials was obtained by mixing polysaccharide chemically crosslinked hydrogels. The mixing was performed by exploiting the thixotropic behaviour of the polysaccharide hydrogels: in other words they were passed through a syringe to subject them to shear stress and render them fluid, then they were mixed together in the fluid state. Once the material regained its consistency, a new hydrogel was obtained, called an inter-penetrating hydrogel (IPH), containing both the native hydrogels. This new class of materials showed different physical-chemical, mechanical and biological properties from the native hydrogels utilized for the mixing. The hydrogels taken into consideration were: negatively charged carboxy methyl cellulose (CMC) and hyaluronic acid (Hyal), uncharged guar gum (GG), and chitosan (CHT), which bore positive charges at physiological pH. The IPHs obtained – i.e. CMC-CHT, CMC-GG and CMC-Hyal – were characterized by means of Fourier transform infrared spectroscopy (FT-IR) and swelling measurements. The mechanical properties of the IPHs were investigated by rheometric analyses, while their morphology was studied by scanning electronic microscopy (SEM). The biological performance of the IPHs was evaluated using fibroblasts (NIH 3T3 cell line) and compared with that of the native hydrogels.

• Bone remodeling, humoral networks and smart biomaterial technology for osteoporosis.

  Authors: Milena Fini, Angelo Carpi, Veronica Borsari, Matilde Tschon, Andrea Nicolini, Maria Sartori, Jeffrey Mechanick, Roberto Giardino

  Frontiers in bioscience (Scholar edition). 01/2010; 2:468-82.

  One of the unfortunate sequelae of increased life expectancy is a growing number of age-related degenerative diseases, a prime example being osteoporosis. This form of metabolic bone disease andOne of the unfortunate sequelae of increased life expectancy is a growing number of age-related degenerative diseases, a prime example being osteoporosis. This form of metabolic bone disease and related co-morbidities consume tremendous resources and costs from a nation's health care system. Osteoporosis results from genetic, age-related, and hormone-dependent causes as well as a compendium of secondary pathophysiological states. The presence of osteoporosis as a comorbidity confers a significant negative prognostic element following orthopedic procedures. In vitro and in vivo studies of osteoporotic bone implicate microarchitectural bone rarefaction, microenvironmental and functional disturbance of osteoblast-osteoclast coupling, and abnormal tissue and signalling molecule repertoires, each having detrimental effects on the regenerative and osteointegration processes. This review explores the pathophysiology of bone remodeling from a macro- and micro- systems biology standpoint with a focus on cytokine interactions. Furthermore, therapeutic interventions exploiting vulnerable nodes in these physiological networks will be posited. One exciting development in this area is the use of novel biomaterials.

• Inhomogeneity of rat vertebrae trabecular architecture by high-field 3D mu-magnetic resonance imaging and variable threshold image segmentation.

  Authors: Marcella Palombarini, Mirko Gombia, Paola Fantazzini, Roberto Giardino, Gianluca Giavaresi, Annapaola Parrilli, Franco Vittur, Genevieve Guillot

  Journal of magnetic resonance imaging : JMRI. 10/2009; 30(4):825-33.

  PURPOSE: To analyze the 3D microarchitecture of rat lumbar vertebrae by micro-magnetic resonance imaging (micro-MRI). MATERIALS AND METHODS: micro-MR images (20 x 20 x 20 microm(3) apparent voxelPURPOSE: To analyze the 3D microarchitecture of rat lumbar vertebrae by micro-magnetic resonance imaging (micro-MRI). MATERIALS AND METHODS: micro-MR images (20 x 20 x 20 microm(3) apparent voxel size) were acquired with a three-dimensional spin-echo pulse sequence on four lumbar vertebrae of two rats. Apparent microarchitectural parameters like trabecular bone fraction (BV/TV), specific bone surface (BS/TV), mean intercept length (MIL), and Euler number per unit volume (Euler density, E(V)) were calculated using a novel semiquantitative variable threshold segmentation technique. The threshold value T was obtained as a point of minimum or maximum of the function E(V) = E(V)(T). RESULTS: Quantitative 3D analysis of micro-MRI images revealed a higher connectivity in the peripheral regions (E(V) = -570 +/- 70 mm(-3)) than in the central regions (E(V) = -130 +/- 50 mm(-3)) of the analyzed rat lumbar vertebrae. Smaller intertrabecular cavities and larger bone volume fractions were observed in peripheral regions as compared to central ones (MIL = 0.18 +/- 0.01 mm and 0.26 +/- 0.01 mm; BV/TV = 34 +/- 3% and 29 +/- 3%, respectively). The quantitative 3D study of MIL showed a structural anisotropy of the trabeculae along the longitudinal axis seen on the images. The inhomogeneity of the bone architecture was validated by micro-computed tomography (micro-CT) images at the same spatial resolution. CONCLUSION: 3D high-field micro-MRI is a suitable technique for the assessment of bone quality in experimental animal models.

• Bone regeneration potential of a soybean-based filler: experimental study in a rabbit cancellous bone defects.

  Authors: Gianluca Giavaresi, Milena Fini, Jonathan Salvage, Nicolò Nicoli Aldini, Roberto Giardino, Luigi Ambrosio, Luigi Nicolais, Matteo Santin

  Journal of materials science. Materials in medicine. 09/2009;

  Autologous and allogenic bone grafts are considered as materials of choice for bone reconstructive surgery, but limited availability, risks of transmittable diseases and inconsistent clinicalAutologous and allogenic bone grafts are considered as materials of choice for bone reconstructive surgery, but limited availability, risks of transmittable diseases and inconsistent clinical performances have prompted the development of alternative biomaterials. The present work compares the bone regeneration potential of a soybean based bone filler (SB bone filler) in comparison to a commercial 50:50 poly(D: ,L: lactide-glycolide)-based bone graft (Fisiograft((R)) gel) when implanted into a critical size defect (6-mm diameter, 10-mm length) in rabbit distal femurs. The histomorphometric and microhardness analyses of femoral condyles 4, 8, 16 and 24 weeks after surgery showed that no significant difference was found in the percentage of both bone repair and bone in-growth in the external, medium and inner defect areas. The SB filler-treated defects showed significantly higher outer bone formation and microhardness results at 24 weeks than Fisiograft((R)) gel (P < 0.05). Soybean-based biomaterials clearly promoted bone repair through a mechanism of action that is likely to involve both the scaffolding role of the biomaterial for osteoblasts and the induction of their differentiation.

• Peritoneal Adhesions to Prosthetic Materials: An Experimental Comparative Study of Treated and Untreated Polypropylene Meshes Placed in the Abdominal Cavity.

  Authors: Luca Ansaloni, Fausto Catena, Federico Coccolini, Milena Fini, Filippo Gazzotti, Roberto Giardino, Antonio Daniele Pinna

  Journal of laparoendoscopic & advanced surgical techniques. Part A. 05/2009;

  Abstract Background: Frequently, hernia repair requires polypropylene (PP) meshes, which carry a well-known adhesiogenic risk when placed in contact to the intestine. The aim of this experimentalAbstract Background: Frequently, hernia repair requires polypropylene (PP) meshes, which carry a well-known adhesiogenic risk when placed in contact to the intestine. The aim of this experimental study in a rat model was to assess the role of some materials, when combined with PP, in preventing the adhesions' formation. Materials and Methods: Sixty male Sprague-Dawley rats were assigned to five groups for intraperitoneal mesh placement: untreated PP, PP+polyurethane (PP+PU), PP+Surgisis (PP+SIS), PP+expanded polytetrafluoroethylene (PP+ePTFE), and a control group without mesh. Twenty-one days and 3 and 6 months after the operation, an assessment of adhesion formation was performed, scoring adhesions in terms of extent and type and the adhesion index (AI; product of adhesions' extent and type). Results: No significant difference was seen between PP+SIS, PP+PU, and control groups in adhesions extent/quality and in AI. The PP+SIS group had significantly lower adhesions' quality value and AI than PP+ePTFE. PP+PU had significantly lower adhesions' extent/quality value and AI than PP+ePTFE. The control group had adhesions with significantly lower extent/quality and AI than PP+ePTFE. The PP group had significantly more and denser adhesions, compared to PP+ePTFE, as well as a significantly higher AI. Conclusions: Adhesions' incidence is reduced by using treated PP meshes. PP+PU and PP+SIS were superior to PP+ePTFE in adhesion prevention.

• Effects of pulsed electromagnetic stimulation on patients undergoing hip revision prostheses: A randomized prospective double-blind study.

  Authors: Dante Dallari, Milena Fini, Gianluca Giavaresi, Nicolandrea Del Piccolo, Cesare Stagni, Luca Amendola, Nicola Rani, Saverio Gnudi, Roberto Giardino

  Bioelectromagnetics. 05/2009;

  In this prospective, randomized, double-blind study, the effect of Pulsed Electromagnetic Fields (PEMFs) was investigated in 30 subjects undergoing hip revision using the Wagner SL stem. The subjectsIn this prospective, randomized, double-blind study, the effect of Pulsed Electromagnetic Fields (PEMFs) was investigated in 30 subjects undergoing hip revision using the Wagner SL stem. The subjects were treated for 6 h/day up to 90 days after revision. Study end points were assessed clinically by the functional scale of Merle D'Aubigné and instrumentally by Dual-Energy X-ray Absorptiometry (DXA) at the Gruen zones. Subject improvement according to Merle D'Aubigné scale was higher (P < 0.05) in subjects undergoing active stimulation compared to placebo. In analyzing the DXA findings, we subtracted for each area the postoperative bone mineral density (BMD) values from those measured at 90 days and we considered all results above 3.5% as responders. There were no significant differences in the average BMD values at each Gruen zone between the two groups both postoperatively and at 90 days investigation. In Gruen zones 5 and 6, corresponding to the medial cortex, we observed six responders (40%) in both areas in the control group, while in the stimulated group we observed 14 (93%) and 10 (66%) responders, respectively (both P < 0.05). This study showed that PEMF treatment aids clinical recovery and bone stock restoration. Bioelectromagnetics, 2009 (c) 2009 Wiley-Liss, Inc.

• Effect of mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defects in the alveolar ridge: a comparative histomorphometric study in minipigs.

  Authors: Francesco Pieri, Enrico Lucarelli, Giuseppe Corinaldesi, Milena Fini, Nicolò Nicoli Aldini, Roberto Giardino, Davide Donati, Claudio Marchetti

  Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 03/2009; 67(2):265-72.

  PURPOSE: The purpose of this study was to test the effect of the combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) incorporated into a fluorohydroxyapatite (FHA) scaffold onPURPOSE: The purpose of this study was to test the effect of the combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) incorporated into a fluorohydroxyapatite (FHA) scaffold on bone regeneration in cylindrical defects in the edentulous mandibular ridge of minipigs. MATERIALS AND METHODS: Two mandibular premolar teeth were extracted bilaterally in 8 adult minipigs. After 2 months, 4 standardized defects of 3.5 mm diameter and 8 mm depth were created in each root site. The defects were randomly grafted with autogenous mandibular bone, FHA alone, PRP-FHA, or MSCs-PRP-FHA. A resorbable collagen membrane was placed over the defect area and the flaps were sutured. The animals were sacrificed 3 months later and biopsy samples were taken from the defect sites for histologic and histomorphometric assessment. RESULTS: There was no evidence of inflammation or adverse tissue reaction with either treatment. MSCs-PRP-FHA-treated sites showed new vital bone between residual grafting particles. PRP-FHA- and FHA-treated sites showed residual particles in a background of marrow soft tissue with a moderate quantity of newly formed bone. Autogenous bone (46.97%) and MSCs-PRP-FHA (45.28%) produced a significantly higher amount of vital bone than PRP-FHA (37.95%), or FHA alone (36.03%). Further, the MSCs-PRP-FHA-treated defects showed a significantly higher percentage of contact between graft particles and newly formed bone compared with PRP-FHA and FHA group (59.23% vs 48.37% and 46.43%, respectively). CONCLUSIONS: Our results suggest that, in this animal model, the addition of MSCs to PRP-FHA enhances bone formation after 3 months.

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• OSTEOARTHRITIS TREATED WITH MESENCHYMAL STEM CELLS ON HYALURONAN-BASED SCAFFOLD IN RABBIT.

  Authors: Brunella Grigolo, Gina Lisignoli, Giovanna Desando, Carola Cavallo, Emanuele Marconi, Matilde Tschon, Gianluca Giavaresi, Milena Fini, Roberto Giardino, Andrea Facchini

  Tissue engineering. Part C, Methods. 03/2009;

  Objective: Osteoarthritis (OA) is a disease that limits the mobility of patients and is of considerable economical importance. To date despite the increasing number of patients with OA, treatments toObjective: Osteoarthritis (OA) is a disease that limits the mobility of patients and is of considerable economical importance. To date despite the increasing number of patients with OA, treatments to manage the condition remain symptomatic, designed to control pain, and improve function and quality of life limiting adverse events. With the aim to explore a new approach to treat OA patients suffering from early degenerative lesions of hyaline cartilage we transplanted in an experimental animal model of OA, a hyaluronan-based scaffold (Hyaff(R)11) seeded with Mesenchymal Stem Cells (MSCs), obtained from bone marrow and expanded in culture. Design: Rabbit knee joints were bilaterally subjected to Anterior Cruciate Ligament Transection (ACLT) to surgically induce OA. After 8 weeks, necessary to the development of cartilage surface damage, animals were treated with mesenchymal stem cells seeded onto Hyaff(R)-11 scaffold in the left condyle and unseeded Hyaff(R)-11 in the controlateral knee. Untreated rabbits were used as control. All the animals were sacrificed at 3 and 6 months after surgery. Histological, histomorphometric and immunohistological evaluations were performed. Results: OA changes developed in all animals subjected to ACLT. The predominant macroscopically observed OA changes were mild (lateral femoral condyle) or moderate (medial femoral condyle) ulcerations. Statistically significant differences in the quality of the regenerated tissue were found between the implants with scaffolds carrying mesenchymal stem cells compared to the scaffold alone or controls in particular at 6 months. Conclusions: From the observations, it is possible to demonstrate that Hyaff(R)-11, a hyaluronan-based scaffold, provides promise for mesenchymal stem cell implantation and that may have application for the treatment of early OA in humans.

• Influence of a zirconia sandblasting treated surface on peri-implant bone healing: An experimental study in sheep.

  Authors: Beatrice Bacchelli, Gianluca Giavaresi, Marco Franchi, Désirée Martini, Viviana De Pasquale, Alessandra Trirè, Milena Fini, Roberto Giardino, Alessandro Ruggeri

  Acta biomaterialia. 02/2009;

  A sandblasting process with round zirconia (ZrO(2)) particles might be an alternative surface treatment to enhance the osseointegration of titanium dental implants. Our previous study on sheepA sandblasting process with round zirconia (ZrO(2)) particles might be an alternative surface treatment to enhance the osseointegration of titanium dental implants. Our previous study on sheep compared smooth surface titanium implants (control) with implant surfaces sandblasted with two different granulations of ZrO(2). As the sandblasted surfaces proved superior, the present study further compared the ZrO(2) surface implant with other surface treatments currently employed: machined titanium (control), titanium oxide plasma sprayed (TPS) and alumina sandblasted (Al-SL) at different times after insertion (2, 4 and 12weeks). Twelve sheep were divided into three groups of four animals each and underwent implant insertion in tibia cortical bone under general anaesthesia. The implants with surrounding tissues were subjected to histology, histomorphometry, scanning electron microscopy and microhardness tests. The experimentation indicated that at 2weeks Zr-SL implants had the highest significant bone ingrowth (p<0.05) compared to the other implant surfaces, and a microhardness of newly formed bone inside the threads significantly higher than that of Ti. The present work shows that the ZrO(2) treatment produces better results in peri-implant newly formed bone than Ti and TPS processing, whereas its performance is similar to the Al-SL surface treatment.

• Covalently-linked hyaluronan promotes bone formation around Ti implants in a rabbit model.

  Authors: Marco Morra, Clara Cassinelli, Giovanna Cascardo, Milena Fini, Gianluca Giavaresi, Roberto Giardino

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 12/2008;

  The goal of this study was the in vivo evaluation of nanoporous titanium (Ti) implants bearing a covalently linked surface hyaluronan (HA) layer. Implant surface topography and surface chemistry wereThe goal of this study was the in vivo evaluation of nanoporous titanium (Ti) implants bearing a covalently linked surface hyaluronan (HA) layer. Implant surface topography and surface chemistry were previously evaluated by scanning electron micorscopy and X-ray photoelectron spectroscopy. Results showed that the surface modification process did not affect surface topography, yielding a homogeneously HA-coated nanotextured implant surface. In vivo evaluation of implants in both cortical and trabecular bone of rabbit femurs showed a significant improvement of both bone-to-implant contact and bone ingrowth at HA-bearing implant interfaces at 4 weeks. The improvement in osteointegration rate was particularly evident in the marrow-rich trabecular bone (bone-to-implant contact: control 22.5%; HA-coated 69.0%, p < 0.01). Mechanical testing (push-out test) and evaluation of interfacial bone microhardness confirmed a faster bone maturation around HA-coated implants (Bone Maturation Index: control 79.1%; HA-coated 90.6%, p < 0.05). Suggestions based on the biochemical role of HA are presented to account for the observed behavior. Published by Wiley Periodicals, Inc. J Orthop Res.

• Alveolar ridge augmentation with titanium mesh and a combination of autogenous bone and anorganic bovine bone: a 2-year prospective study.

  Authors: Francesco Pieri, Giuseppe Corinaldesi, Milena Fini, Nicolò Nicoli Aldini, Roberto Giardino, Claudio Marchetti

  Journal of periodontology. 11/2008; 79(11):2093-103.

  BACKGROUND: Recently, the use of bovine bone mineral (BBM) in combination with autogenous bone for alveolar ridge augmentation before implant placement has increased in favor because of concerns overBACKGROUND: Recently, the use of bovine bone mineral (BBM) in combination with autogenous bone for alveolar ridge augmentation before implant placement has increased in favor because of concerns over morbidity associated with extraoral donor sites. The aim of this prospective study was to evaluate the clinical and radiographic parameters of implants placed in augmented ridges using a 70:30 mixture of autogenous bone and BBM in association with micro-mesh over a 2-year period. METHODS: Sixteen partially edentulous patients requiring bone augmentation were consecutively treated for 19 reconstructive procedures and delayed implant placement (44 implants) after 8 to 9 months of submerged mesh healing. Clinical examinations were performed and radiographs of the implants were taken 6 months after prosthetic loading and once a year during a 2-year follow-up. RESULTS: Only one (5.3%) of the 19 micro-meshes became exposed after 2 months and was removed. Computed tomography scans of the alveolar ridge pre- and postreconstruction demonstrated mean vertical augmentation of 3.71 +/- 1.24 mm and mean horizontal augmentation of 4.16 +/- 0.59 mm. All of the implants were retained after 2 years, yielding a 100% survival rate. The mean bone resorption around the implants was 1.37 +/- 0.32 mm during the observation period. Only three implants demonstrated bone resorption >2 mm, whereas 41 implants were considered clinically successful, resulting in a success rate of 93.1%. CONCLUSION: This 2-year prospective study demonstrated that implants placed into augmented bone using this technique exhibited peri-implant stability with high survival (100%) and success (93.1%) rates.

• Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study.

  Authors: Antonio Barone, Nicolò Nicoli Aldini, Milena Fini, Roberto Giardino, José Luis Calvo-Guirado, Ugo Covani

  Journal of periodontology. 09/2008; 79(8):1370-7.

  BACKGROUND: The preservation of bone volume immediately after tooth removal might be necessary to optimize the success of implant placement in terms of esthetics and function. The objectives of thisBACKGROUND: The preservation of bone volume immediately after tooth removal might be necessary to optimize the success of implant placement in terms of esthetics and function. The objectives of this randomized clinical trial were two-fold: 1) to compare the bone dimensional changes following tooth extraction with extraction plus ridge preservation using corticocancellous porcine bone and a collagen membrane; and 2) to analyze and compare histologic and histomorphometric aspects of the extraction-alone sites to the grafted sites. METHODS: Forty subjects who required tooth extraction and implant placement were enrolled in this study. Using a computer-generated randomization list, the subjects were randomly assigned to the control group (EXT; extraction alone) or to the test group (RP; ridge-preservation procedure with corticocancellous porcine bone and collagen membrane). The following parameters were assessed immediately after extraction and 7 months prior to implant placement: plaque index, gingival index, bleeding on probing, horizontal ridge width, and vertical ridge changes. A bone biopsy was taken from the control and test sites 7 months after the surgical treatment. Histologic and histomorphometric analyses were also performed. RESULTS: A significantly greater horizontal reabsorption was observed at EXT sites (4.3+/-0.8 mm) compared to RP sites (2.5+/-1.2 mm). The ridge height reduction at the buccal side was 3.6+/-1.5 mm for the extraction-alone group, whereas it was 0.7+/-1.4 mm for the ridge-preservation group. Moreover, the vertical change at the lingual sites was 0.4 mm in the ridge-preservation group and 3 mm in the extraction-alone group. Forty biopsies were harvested from the experimental sites (test and control sites). The biopsies harvested from the grafted sites revealed the presence of trabecular bone, which was highly mineralized and well structured. Particles of the grafted material could be identified in all samples. The bone formed in the control sites was also well structured with a minor percentage of mineralized bone. The amount of connective tissue was significantly higher in the extraction-alone group than in the ridge-preservation group. CONCLUSIONS: The ridge-preservation approach using porcine bone in combination with collagen membrane significantly limited the resorption of hard tissue ridge after tooth extraction compared to extraction alone. Furthermore, the histologic analysis showed a significantly higher percentage of trabecular bone and total mineralized tissue in ridge-preservation sites compared to extraction-alone sites 7 months after tooth removal.

• An amidated carboxymethylcellulose hydrogel for cartilage regeneration.

  Authors: Gemma Leone, Milena Fini, Paola Torricelli, Roberto Giardino, Rolando Barbucci

  Journal of materials science. Materials in medicine. 09/2008; 19(8):2873-80.

  An amidic derivative of carboxymethylcellulose was synthesized (CMCA). The new polysaccharide was obtained by converting a large percentage of carboxylic groups ( approximately 50%) ofAn amidic derivative of carboxymethylcellulose was synthesized (CMCA). The new polysaccharide was obtained by converting a large percentage of carboxylic groups ( approximately 50%) of carboxymethylcellulose into amidic groups rendering the macromolecule quite similar to hyaluronan. Then, the polysaccharide (CMCA) was crosslinked. The behavior of CMCA hydrogel towards normal human articular chondrocytes (NHAC) was in vitro studied monitoring the cell proliferation and synthesis of extra cellular matrix (ECM) components and compared with a hyaluronan based hydrogel (Hyal). An extracellular matrix rich in cartilage-specific collagen and proteoglycans was secreted in the presence of hydrogels. The injectability of the new hydrogels was also analysed. An experimental in vivo model was realized to study the effect of CMCA and Hyal hydrogels in the treatment of surgically created partial thickness chondral defects in the rabbit knee. The preliminary results pointed out that CMCA hydrogel could be considered as a potential compound for cartilage regeneration.