Laboratory of Biocompatibility

Bologna, Italy

Laboratory of Biocompatibility

Bologna, Italy
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Filardo G.,Rizzoli Orthopaedic Institute | Kon E.,Rizzoli Orthopaedic Institute | Tampieri A.,National Research Council Italy | Cabezas-Rodriguez R.,University of Seville | And 14 more authors.
Tissue Engineering - Part A | Year: 2014

Bone loss is still a major problem in orthopedics. The purpose of this experimental study is to evaluate the safety and regenerative potential of a new scaffold based on a bio-ceramization process for bone regeneration in long diaphyseal defects in a sheep model. The scaffold was obtained by transformation of wood pieces into porous biomorphic silicon carbide (BioSiC®). The process enabled the maintenance of the original wood microstructure, thus exhibiting hierarchically organized porosity and high mechanical strength. To improve cell adhesion and osseointegration, the external surface of the hollow cylinder was made more bioactive by electrodeposition of a uniform layer of collagen fibers that were mineralized with biomimetic hydroxyapatite, whereas the internal part was filled with a bio-hybrid HA/collagen composite. The final scaffold was then implanted in the metatarsus of 15 crossbred (Merinos-Sarda) adult sheep, divided into 3 groups: scaffold alone, scaffold with platelet-rich plasma (PRP) augmentation, and scaffold with bone marrow stromal cells (BMSCs) added during implantation. Radiological analysis was performed at 4, 8, 12 weeks, and 4 months, when animals were sacrificed for the final radiological, histological, and histomorphometric evaluation. In all tested treatments, these analyses highlighted the presence of newly formed bone at the bone scaffolds' interface. Although a lack of substantial effect of PRP was demonstrated, the scaffold+BMSC augmentation showed the highest value of bone-to-implant contact and new bone growth inside the scaffold. The findings of this study suggest the potential of bio-ceramization processes applied to vegetable hierarchical structures for the production of wood-derived bone scaffolds, and document a suitable augmentation procedure in enhancing bone regeneration, particularly when combined with BMSCs. © 2014 Mary Ann Liebert, Inc.


Della Bella E.,Rizzoli Orthopaedic Institute | Della Bella E.,University of Bologna | Cepollaro S.,Rizzoli Orthopaedic Institute | Cepollaro S.,University of Bologna | And 5 more authors.
Cytotherapy | Year: 2016

Osteoarthritis (OA) can affect every joint, especially the knee. Given the complexity of this pathology, OA is difficult to treat with current therapies, which only relieve pain and inflammation and are not capable of restoring tissues once OA has started. Currently, researchers focus on finding a therapeutic strategy that may help to arrest disease progression.The present narrative review gives an overview of the genes involved in the development and progression of OA, assessing in vivo studies performed in knock-out mice affected by OA, to suggest new therapeutic strategies. The article search was performed on the PubMed database and www.webofknowledge.com website with the following keywords: "knee osteoarthritis" AND "knockout mice". The included studies were in English and published from 2005 to 2015. Additional papers were found within the references of the selected articles. In the 55 analyzed in vivo studies, genes mainly affected chondrocyte homeostasis, inflammatory processes, extracellular matrix and the relationship between obesity and OA. Genes are defined as inducing, preventing and not influencing OA. This review shows that joint homeostasis depends on a variety of genetic factors, and preventing or restoring the loss of a gene encoding for protective proteins, or inhibiting the expression of proteins that induce OA, might be a potential therapeutic approach. However, conclusions cannot be drawn because of the wide variability concerning the technique used for OA induction, the role of the genes, the method for tissue evaluations and the lack of assessments of all joint tissues. © 2016 International Society for Cellular Therapy.


Torricelli P.,Rizzoli Orthopaedic Institute | Torricelli P.,Laboratory of Biocompatibility | Veronesi F.,Rizzoli Orthopaedic Institute | Pagani S.,Rizzoli Orthopaedic Institute | And 6 more authors.
Age | Year: 2013

Little is known about tendons and tenocyte biological behaviour during aging and, especially, oestrogen deficiency. The aim of this study was to evaluate in vitro the proliferation and metabolism of tenocytes isolated from the Achilles tendons of ovariectomised (OVX), middle-aged (OLD) and young (YOUNG) rats. An in vitro model of micro-wound healing was also used to assess age and oestrogen deficiency differences in tendon healing. In standard culture condition, OLD and OVX tenocytes showed a significantly lower proliferation rate, collagen I, aggrecan and elastin than YOUNG ones. In OVX group, fibronectin and elastin significantly decreased in comparison to YOUNG and OLD groups, respectively, whereas vascular endothelial growth factor and metalloproteinases-13 increased than those of both YOUNG and OLD groups. In the microwound healing model, tenocytes from both OVX andj OLD showed a significantly lower healing rate, proliferation rate, collagen I and nitrix oxide in comparison to YOUNG. OVX elastin value was significantly lower than YOUNG one and OVX healing rate and cell migration speed, proliferation rate and fibronectin results were lower, whereas collagen III and metalloproteinase-13 higher in comparison to both YOUNG and OLD groups. These results highlighted how aging and, more significantly, oestrogen deficiency negatively affect tendon metabolism and healing. Our work improves the body of knowledge on the effects of senescence and oestrogen deficiency on tenocyte behaviour and allows further studies to find solution for the prevention of tendon injuries in aging and menopause. © American Aging Association 2012.


Veronesi F.,Rizzoli Orthopaedic Institute | Pagani S.,Rizzoli Orthopaedic Institute | Pagani S.,Laboratory of Biocompatibility | Della Bella E.,Rizzoli Orthopaedic Institute | And 4 more authors.
Age | Year: 2014

Osteoporosis due to estrogen deficiency is an increasing bone health issue worldwide: new strategies are being studied for regenerative medicine of bone pathologies in these patients. The most commonly used cells for tissue engineering therapy are the bone marrow mesenchymal stem cells (BMSCs), but they might be negatively affected by aging and estrogen deficiency. Besides the general advantages of adipose-derived mesenchymal stem cells (ADSCs) over BMSCs, ADSCs also seem to be less affected by aging than BMSCs, but in the literature, little is known about ADSCs in estrogen deficiency. The present study investigated the in vitro behavior of ADSCs, isolated from healthy (SHAM) and estrogen-deficient (OVX) rats. Phenotype, clonogenicity, viability, and osteogenic differentiation, at both cellular and molecular levels, were evaluated with or without osteogenic stimuli. Pro-inflammatory cytokines, growth factors, and adipogenic differentiation markers were also analyzed. There were no significant differences between OVX and SHAM ADSCs in some analyzed parameters. In addition, clonogenicity, osteopontin (Spp1) gene expression, alkaline phosphatase (ALP) activity at 2 weeks of culture, total collagen (COLL), osteocalcin (Bglap) gene expression and production, and matrix mineralization were significantly higher in OVX than in SHAM ADSCs. Besides the increase in some osteogenic markers, peroxisome proliferator-activated receptor gamma (Pparg) gene was also more expressed in OVX in osteogenic medium, with a concomitant estrogen receptor 1 (Esr1) gene expression decrease. These results underlined that ADSCs were not affected by estrogen deficiency in an osteogenic microenvironment. © 2014 American Aging Association.


Guarino V.,National Research Council Italy | Veronesi F.,Laboratory of Biocompatibility | Marrese M.,National Research Council Italy | Giavaresi G.,Laboratory of Biocompatibility | And 7 more authors.
Biomedical Materials (Bristol) | Year: 2016

Surface topography and chemistry both play a crucial role on influencing cell response in 3D porous scaffolds in terms of osteogenesis. Inorganic materials with peculiar morphology and chemical functionalities may be proficiently used to improve scaffold properties - in the bulk and along pore surface - promoting in vitro and in vivo osseous tissue in-growth. The present study is aimed at investigating how bone regenerative properties of composite scaffolds made of poly(ε-caprolactone) (PCL) can be augmented by the peculiar properties of Mg2+ ion doped hydroxyapatite (dHA) crystals, mainly emphasizing the role of crystal shape on cell activities mediated by microstructural properties. At the first stage, the study of mechanical response by crossing experimental compression tests and theoretical simulation via empirical models, allow recognizing a significant contribution of dHA shape factor on scaffold elastic moduli variation as a function of the relative volume fraction. Secondly, the peculiar needle-like shape of dHA crystals also influences microscopic (i.e. crystallinity, adhesion forces) and macroscopic (i.e. roughness) properties with relevant effects on biological response of the composite scaffold: differential scanning calorimetry (DSC) analyses clearly indicate a reduction of crystallization heat - from 66.75 to 43.05 J g-1 - while atomic force microscopy (AFM) ones show a significant increase of roughness - from (78.15 ± 32.71) to (136.13 ± 63.21) nm - and of pull-off forces - from 33.7% to 48.7%. Accordingly, experimental studies with MG-63 osteoblast-like cells show a more efficient in vitro secretion of alkaline phosphatase (ALP) and collagen I and a more copious in vivo formation of new bone trabeculae, thus suggesting a relevant role of dHA to support the main mechanisms involved in bone regeneration. © 2016 IOP Publishing Ltd.


Torricelli P.,Rizzoli Orthopaedic Institute | Torricelli P.,Laboratory of Biocompatibility | Gioffre M.,University of Bologna | Fiorani A.,University of Bologna | And 6 more authors.
Materials Science and Engineering C | Year: 2014

Bio-synthetic scaffolds of interspersed poly(l-lactic acid) (PLLA) and gelatin (GEL) fibers are fabricated by co-electrospinning. Tailored PLLA/GEL compositions are obtained and GEL crosslinking with genipin provides for the maintenance of good fiber morphology. Scaffold tensile mechanical properties are intermediate between those of pure PLLA and GEL and vary as a function of PLLA content. Primary human chondrocytes grown on the scaffolds exhibit good proliferation and increased values of the differentiation parameters, especially for intermediate PLLA/GEL compositions. Mineralization tests enable the deposition of a uniform layer of poorly crystalline apatite onto the scaffolds, suggesting potential applications involving cartilage as well as cartilage-bone interface tissue engineering. © 2013 Elsevier B.V. All rights reserved.


Fini M.,Rizzoli Orthopaedic Institute | Fini M.,Laboratory of Biocompatibility | Giavaresi G.,Rizzoli Orthopaedic Institute | Giavaresi G.,Laboratory of Biocompatibility | And 7 more authors.
Journal of Bone and Mineral Metabolism | Year: 2011

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 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. © 2011 The Japanese Society for Bone and Mineral Research and Springer.


Veronesi F.,Rizzoli Orthopaedic Institute | Torricelli P.,Rizzoli Orthopaedic Institute | Torricelli P.,Laboratory of Biocompatibility | Della Bella E.,Rizzoli Orthopaedic Institute | And 5 more authors.
Cytotherapy | Year: 2015

Background aims: Tendon is a complex tissue with a reduced regenerative ability. Nowadays, little or nothing is known about the regenerative effect of adipose-derived mesenchymal stromal cells (ADSCs) on tendons. Methods: The study aimed to evaluate the invitro mutual interaction of ADSCs and tenocytes in standard culture conditions and a microwound healing model. Tenocyte viability, microwound recovery and the expression of genes encoding for the main extracellular matrix components and ADSC viability, differentiation and growth factor gene expression were evaluated. Results: The effects of ADSCs on tenocytes were observed more in the microwound healing model, in which the rate of microwound healing and the expression of decorin, tenascin and collagens were significantly increased. The influence of tenocytes on ADSCs was also found in standard culture conditions: ADSCs were directed toward a tenogenic lineage, and growth factor expression increased. Conclusions: This study clarifies some aspects of the mutual interaction of ADSCs and tenocytes and provides invitro evidence for a possible future application of ADSCs as a therapeutic strategy for tendon repair. © 2015 International Society for Cellular Therapy.


Veronesi F.,Rizzoli Orthopaedic Institute | Della Bella E.,Rizzoli Orthopaedic Institute | Della Bella E.,University of Bologna | Torricelli P.,Rizzoli Orthopaedic Institute | And 5 more authors.
Cytotherapy | Year: 2015

Background aims: Aging and estrogen deficiency play a pivotal role in reducing tenocyte proliferation, collagen turnover and extracellular matrix remodeling. Mesenchymal stromal cells are being studied as an alternative for tendon regeneration, but little is known about the molecular events of adipose-derived mesenchymal stromal cells (ADSCs) on tenocytes in tendons compromised by aging and estrogen deficiency. The present in vitro study aims to compare the potential therapeutic effects of ADSCs, harvested from healthy young (sham) and aged estrogen-deficient (OVX) subjects, for tendon healing. Methods: An indirect co-culture system was set up with ADSCs, isolated from OVX or sham rats, and tenocytes from OVX rats. Cell proliferation, healing rate and gene expression were evaluated in both a standard culture condition and a microwound-healing model. Results: It was observed that tenocyte proliferation, healing rate and collagen expression improved after the addition of sham ADSCs in both culture situations. OVX ADSCs also increased tenocyte proliferation and healing rate but less compared with sham ADSCs. Decorin and Tenascin C expression increased in the presence of OVX ADSCs. Conclusions: Findings suggest that ADSCs might be a promising treatment for tendon regeneration in advanced age and estrogen deficiency. However, some differences between allogenic and autologous cells were found and should be investigated in further in vivo studies. It appears that allogenic ADSCs improve tenocyte proliferation, collagen expression and the healing rate more than autologous cells. Autologous cells increase collagen expression only in the absence of an injury and increase Decorin and Tenascin C more than allogenic cells. © 2015 International Society for Cellular Therapy.


PubMed | Laboratory of Biocompatibility, University of Bologna and Rizzoli Orthopaedic Institute
Type: Journal Article | Journal: Histology and histopathology | Year: 2015

To reduce the burden of bone metastases, the pathophysiology of the metastatic niche should be elucidated and targeted. The aim of the present study was to assess the effect of tumor cells on osteoclast (OC) recruitment and activity in the presence of altered bone remodelling. Peripheral blood mononuclear cells (PBMC) were isolated from healthy and ovariectomized (OVX) rats and co-cultured with MRMT-1 rat breast carcinoma cells or with their conditioned medium for 1 and 2 weeks. Alamar Blue viability test, synthesis of cathepsin K, transforming growth factor-beta 1 (TGF-1), tumor necrosis factor alpha (TNF-), vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-7, MMP-9, FITC-conjugate phalloidin staining and tartrate-resistant acid phosphatase (TRAP) staining were evaluated. The results indicate that breast carcinoma cells induced different responses in PBMC derived from rats affected by estrogen deficiency osteoporosis (OP) in comparison with healthy ones, with a significant increase in proliferation rate, OC differentiation, synthesis of TNF-, MMP-7 and MMP-9. The data support the proof of concept that OP due to estrogen deficiency might offer a receptive site for cancer cells to form bone metastases.

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