Gianluca Giavaresi

Publications of Gianluca Giavaresi

• TISSUE ENGINEERING FOR TOTAL MENISCAL SUBSTITUTION. Animal study in sheep model: results at 12 months.

  Authors: Elizaveta Kon, Giuseppe Filardo, Matilde Tschon, Milena Fini, Gianluca Giavaresi, Leonardo Marchesini Reggiani, Catharina Chiari, Stefan Nehrer, Ivan Martin, Donald Salter, Luigi Ambrosio, Maurilio Marcacci

  Tissue engineering. Part A. 04/2012;

  The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of theThe aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided in three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At 12 months gross assessment, histology and histomorphometry were used to assess meniscus implant, knee joint and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. Implant gross assessment showed significant differences between cell-seeded and cell-free groups (p=0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those who underwent meniscectomy (p<0.0005), and OARSI score showed that osteoarthritic changes were significantly less in the cell-seeded group than in meniscectomy group (p=0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.

• 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.

• Dental implant thread pitch and its influence on the osseointegration process: an in vivo comparison study.

  Authors: Ester Orsini, Gianluca Giavaresi, Alessandra Trire, Vittoria Ottani, Stefano Salgarello

  The International journal of oral & maxillofacial implants. 03/2012; 27(2):383-92.

  Purpose: The design of an implant plays a fundamental role in the osseointegration process, particularly in low-density bone. It has been postulated that design features that maximize the surfacePurpose: The design of an implant plays a fundamental role in the osseointegration process, particularly in low-density bone. It has been postulated that design features that maximize the surface area available for contact may improve mechanical anchorage and primary stability in cancellous bone. Two different implant profiles were compared to evaluate the influence of thread pitch on the osseointegration process in bone of low density and limited height. Materials and Methods: ?Narrow-pitch? implants (NP) with a 0.5-mm pitch and ?wide-pitch? implants (WP) with a 1.7-mm pitch were tested for osseointegration after 0 days and 4 and 8 weeks in a sheep iliac crest model. The two different implants were analyzed with biologic and biomechanical tests. Results: The present findings showed that initial mechanical anchorage and subsequent early endosseous integration in low-density bone could be improved by a reduction of thread pitch. The greater surface area gained by decreasing thread pitch increased bone-implant contact and primary stability from the time of implant placement. This better performance of the NP profile could be appreciated even at an early healing time when the subsequent biologic integration was enhanced not only in terms of a higher quantity of newly deposited bone but also more regular and mature geometric distribution of bone tissue at the interface. Conclusion: These results confirmed that, when primary stability is a concern, as in cancellous bone, increasing the implant surface area by using implants with smaller pitch might be beneficial.

• 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.

• Long-term Results following a Cranial Hydroxyapatite Prosthesis implantation in a large Skull Defect Model.

  Authors: Lucia Martini, Guido Staffa, Gianluca Giavaresi, Francesca Salamanna, Annapaola Parrilli, Elena Serchi, Daniele Pressato, Elena Arcangeli, Milena Fini

  Plastic and reconstructive surgery. 12/2011;

  BACKGROUND:: A large skull defect may occur after different events such as trauma, tumour resection, vascular injuries etc. There is still some doubt about the best material to use forBACKGROUND:: A large skull defect may occur after different events such as trauma, tumour resection, vascular injuries etc. There is still some doubt about the best material to use for reconstruction. Hydroxyapatite ceramic is one of the materials in use and its biocompatibility and osteoconductivity are well established. OBJECT:: This study evaluated the interaction of a commercial hydroxyapatite custom-made prosthesis implanted in a large skull defect, to assess its osteointegration and its habitability with new formed bone over time. METHODS:: Ten sheep underwent craniectomy and reconstruction of the skull defect with a porous hydroxyapatite cranial prosthesis. The animals were divided into two groups: Group A was sacrificed after 6 months and Group B after 12 months. At the end of the experimental times each implant was evaluated macroscopically, radiologically and analyzed by micro-CT, histology, histomorphometry and microhardness techniques. RESULTS:: During the study no adverse events occurred and there was no evidence of inflammation or negative tissue reactions. Histology and histomorphometry showed new bone formation inside the implant at both experimental times; newly formed bone had increased significantly (p <0.05) by over 300% between 6 and 12 months. 3D micro-CT analysis showed new bone formation and material remodeling. Microhardness analysis indicated that the mineralization process and the mechanical properties of newly formed bone were not altered. CONCLUSIONS:: The hydroxyapatite prosthesis showed its osteoconductivity and good biocompatibility. A low rate of fibrous tissue formation and a high rate of bony regeneration was found.

• Harmful lifestyles on orthopedic implantation surgery: a descriptive review on alcohol and tobacco use.

  Authors: Milena Fini, Gianluca Giavaresi, Francesca Salamanna, Francesca Veronesi, Lucia Martini, Monica De Mattei, Matilde Tschon

  Journal of bone and mineral metabolism. 09/2011; 29(6):633-44.

  Alcohol abuse and smoking habits have adverse effects on bone health and are a risk factor for osteoporosis, fractures and impaired fracture repair. Osteointegration processes around implantedAlcohol abuse and smoking habits have adverse effects on bone health and are a risk factor for osteoporosis, fractures and impaired fracture repair. Osteointegration processes around implanted biomaterials involve a coordinated cascade of complex events that are very similar to those occurring during fracture repair and require a suitable microenvironment and the coordinated action of cells and signal molecules. Therefore, diseases and harmful lifestyles that impair the normal bone healing process can reduce the success of implant surgery and may negatively influence the osteointegration of prostheses and implant devices for fracture fixation such as screws, nails and plates. Understanding the effects of harmful lifestyles on bone implant osteointegration is important for successful implant therapy, orthopedic reconstructive surgery and tissue-engineered-based therapies. However, the mechanisms by which smoking and alcoholism affect bone metabolism, bone mass and the balance of bone resorption and formation, also in the presence of an orthopedic implant, are not completely understood and remain inadequately elucidated. This review aims to analyze in vitro and in vivo studies regarding orthopedic implant integration in the presence of tobacco smoking and alcohol consumption with a focus on pathophysiology and local or systemic mechanisms of action on bone.

• Microbiological and pharmacological tests on new antibiotic-loaded PMMA-based composites for the treatment of osteomyelitis.

  Authors: Gianluca Giavaresi, Elisa Bertazzoni Minelli, Maria Sartori, Anna Benini, Tommaso Della Bora, Vittorio Sambri, Paolo Gaibani, Veronica Borsari, Francesca Salamanna, Lucia Martini, Nicolò Nicoli Aldini, Milena Fini

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 08/2011; 30(3):348-55.

  Local antibiotic diffusion in rabbit femurs from two new PMMA-based and nail-shaped composites, enriched with β-tricalcium phosphate (P-TCP) and BaSO(4) or only with BaSO(4) (P-BaSO(4) ), and soakedLocal antibiotic diffusion in rabbit femurs from two new PMMA-based and nail-shaped composites, enriched with β-tricalcium phosphate (P-TCP) and BaSO(4) or only with BaSO(4) (P-BaSO(4) ), and soaked in a solution of gentamicin (G) and vancomycin (V) was studied. Nails were implanted into the intramedullary cavity of healthy and osteomyelitic femurs to study the resolution of infection and to quantify the antibiotic penetration into bone by microbiological, pharmacological, and histological tests. A significant progression of osteomyelitis was recorded 7 weeks after MRSA inoculation, whereas no bacteria were found in animals treated with antibiotic-loaded nails as confirmed by microbiology and histology (Smeltzer score). The release of both antibiotics from composites was high and prompt both in healthy and infected bone; the amount of V was higher than that of G in all bone samples. Antibiotics of both composites were still present in bone 3 weeks after nail implantation. The P-BaSO4 composite released a lower amount of antibiotics than did P-TCP. The G-V combination in vivo exerted a synergistic bactericidal effect, which was confirmed by microbiological, histological, and clinical results (no infection). These new porous PMMA composites, soaked in G-V solution in the operating room, might be an effective and useful drug delivery system for osteomyelitis treatment.

• 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.

• 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.

• Mesenchymal stem cells and platelet lysate in fibrin or collagen scaffold promote non-cemented hip prosthesis integration.

  Authors: Barbara Dozza, Claudia Di Bella, Enrico Lucarelli, Gianluca Giavaresi, Milena Fini, Pier Luigi Tazzari, Sandro Giannini, Davide Donati

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 01/2011; 29(6):961-8.

  The objective of this study was to evaluate whether mesenchymal stem cells (MSC) and platelet lysate (PL) seeded in a fibrin or collagen scaffold could improve the new bone (NB) formation around anThe objective of this study was to evaluate whether mesenchymal stem cells (MSC) and platelet lysate (PL) seeded in a fibrin or collagen scaffold could improve the new bone (NB) formation around an uncemented hip prosthesis stem in a sheep model. In vitro expanded MSC were suspended in PL and either mixed with collagen or fibrin gel as delivery vehicle. The cell-gel composites were inserted inside the femoral canal, then the prosthesis was press-fit inserted inside the femur. Identical procedures were performed in a control group, but only the prosthesis was implanted. Histomorphometrical analysis performed 4 months after surgery indicated that the newly formed bone inside the medullary canal, between the inner cortex and the prosthetic stem, was significantly higher in the MSC-PL-collagen group (mean 18.7 ± 4.5%) and in the MSC-PL-fibrin group (mean 18.8 ± 15.2%) when compared to the control group (mean 4.6 ± 2.0%). There was a significantly higher bone-prosthesis contact in the MSC-PL-collagen group (mean 2.7 ± 2.6%) and in the MSC-PL-fibrin group (mean 2.3 ± 3.1%) compared to the control group (mean 0.2 ± 0.1%). The results indicate that MSC and PL in a fibrin or collagen scaffold can promote NB formation around an uncemented hip prosthesis stem.

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• Total hip arthroplasty with shortening osteotomy in congenital major hip dislocation sequelae.

  Authors: Dante Dallari, Giovanni Pignatti, Cesare Stagni, Gianluca Giavaresi, Nicolandrea Del Piccolo, Nicola Rani, Francesca Veronesi, Milena Fini

  Orthopedics. 01/2011; 34(8):e328-33.

  We retrospectively evaluated the postoperative results of total hip arthroplasty (THA) in patients presenting with Crowe group IV dislocated hips. Overall, results were compared with regard to theWe retrospectively evaluated the postoperative results of total hip arthroplasty (THA) in patients presenting with Crowe group IV dislocated hips. Overall, results were compared with regard to the type of osteotomy performed (Z or oblique) to define the correct indications for surgical technique and choice of prosthetic implant. Thirty-three subtrochanteric shortening and derotational osteotomies in primary THA were performed in 26 patients secondary to congenital hip dislocation. A Z osteotomy was performed in 14 cases and an oblique osteotomy in 19. The surgical approach was direct lateral, and surgery was aimed at restoring the anatomic hip center. Femoral and acetabular fixation was uncemented. The most used stem was the S-ROM (DePuy, Leeds, United Kingdom), and the couplings used were ceramic-ceramic (7 cases), ceramic-polyethylene (3 cases), metal-polyethylene (15 cases), and metal-metal (3 cases). Mean follow-up was 88±45 months. According to the Merle D'Aubigné score, the overall clinical results were good in 23 cases, satisfactory in 6, and fair in 4. Union of the osteotomy occurred in 97% of cases, and the mean time required for osteotomy union was 6±2 months without significant differences between Z and oblique osteotomies. At last follow-up, there was loosening of 1 cup and 1 stem, and revision was necessary. Twelve percent of patients experienced postoperative dislocation and 9% developed neuropraxia of the femoral nerve. The clinical and radiological results were similar in both groups, with a high rate of pain relief, an improvement in limb-length discrepancy, and reduced limping, leading to a smaller or no insole. Currently, the more complex Z osteotomy has been abandoned, because a modular stem prosthesis with metaphyseal sleeve allows the oblique osteotomy to be used with an easier and shorter surgical procedure.

• Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model.

  Authors: Elizaveta Kon, Giuseppe Filardo, Marco Delcogliano, Milena Fini, Francesca Salamanna, Gianluca Giavaresi, Ivan Martin, Maurilio Marcacci

  BMC musculoskeletal disorders. 01/2010; 11:220.

  Current research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-richCurrent research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-rich plasma (PRP) to enhance the repair process of a collagen-hydroxyapatite scaffold in osteochondral defects in a sheep model. PRP was added to a new, multi-layer gradient, nanocomposite scaffold that was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Twenty-four osteochondral lesions were created in sheep femoral condyles. The animals were randomised to three treatment groups: scaffold, scaffold loaded with autologous PRP, and empty defect (control). The animals were sacrificed and evaluated six months after surgery. Gross evaluation and histology of the specimens showed good integration of the chondral surface in both treatment groups. Significantly better bone regeneration and cartilage surface reconstruction were observed in the group treated with the scaffold alone. Incomplete bone regeneration and irregular cartilage surface integration were observed in the group treated with the scaffold where PRP was added. In the control group, no bone and cartilage defect healing occurred; defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The hydroxyapatite-collagen scaffold enhanced osteochondral lesion repair, but the combination with platelet growth factors did not have an additive effect; on the contrary, PRP administration had a negative effect on the results obtained by disturbing the regenerative process. In the scaffold + PRP group, highly amorphous cartilaginous repair tissue and poorly spatially organised underlying bone tissue were found.

• 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.

• Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial.

  Authors: Elizaveta Kon, Marco Delcogliano, Giuseppe Filardo, Milena Fini, Gianluca Giavaresi, Silvia Francioli, Ivan Martin, Daniele Pressato, Elena Arcangeli, Rodolfo Quarto, Monica Sandri, Maurillo Marcacci

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 08/2009;

  The objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A newThe objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A new multilayer gradient nano-composite scaffold was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. In the femoral condyles of 12 sheep, 24 osteochondral lesions were created. Animals were randomized into three treatment groups: scaffold alone, scaffold colonized in vitro with autologous chondrocytes and empty defects. Six months after surgery, the animals were sacrificed and the lesions were histologically evaluated. Histologic and gross evaluation of specimens showed good integration of the chondral surface in all groups except for the control group. Significantly better bone regeneration was observed both in the group receiving the scaffold alone and in the group with scaffold loaded with autologous chondrocytes. No difference in cartilage surface reconstruction and osteochondral defect filling was noted between cell-seeded and cell-free groups. In the control group, no bone or cartilage defect healing occurred, and the defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The results of the present study showed that this novel osteochondral scaffold is safe and easy to use, and may represent a suitable matrix to direct and coordinate the process of bone and hyaline-like cartilage regeneration. The comparable regeneration process observed with or without autologous chondrocytes suggests that the main mode of action of the scaffold is based on the recruitment of local cells. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

• 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.

• 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.

• A novel multiphase anodic spark deposition coating for the improvement of orthopedic implant osseointegration: an experimental study in cortical bone of sheep.

  Authors: Gianluca Giavaresi, Milena Fini, Roberto Chiesa, Carmen Giordano, Enrico Sandrini, Andrea E Bianchi, Paolo Ceribelli, Roberto Giardino

  Journal of biomedical materials research. Part A. 07/2008; 85(4):1022-31.

  The effect of a new three-step anodic spark deposition process, labeled TiSpark, including two consecutive treatments performed first in a P solution and second in Ca solution, followed by anThe effect of a new three-step anodic spark deposition process, labeled TiSpark, including two consecutive treatments performed first in a P solution and second in Ca solution, followed by an additional alkali etching step, was investigated for the improvement of osseointegration of commercial grade 2 titanium, machined (Ti) or Al(2)O(3) sandblasted (Ti-SA), cylindrical implants (12 mm in length and 4 mm in diameter) in cortical bone of 12 adult sheep. Histomorphometric and microhardness measurements were carried out at each experimental time (4, 8, and 12 weeks) to quantify the bone-to-implant contact around the implants as well as the newly bone hardness and bone maturation index. TiSpark treated surfaces were covered by a thick layer of crystalline anatase TiO(2) and by a further Ca/P layer. Bone tissue extends and grows on the surface of the TiSpark treated implants without any fibrous tissue, enhancing the short-term osseointegration properties of implant. Bone mineralization rate was also influenced by the chemical composition of implants and sandblasted materials presented the lowest bone maturation rate at the interface. Data suggests that the TiSpark treatment produces a modification of the Ti surface, which presents good bioactivity and may be suitable for achieving a stable implant osseointegration.