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Castel Guelfo di Bologna, Italy

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.


Nicoletti A.,Fin Ceramica Faenza S.p.A. | Torricelli P.,Laboratory of Preclinical and Surgical Studies | Torricelli P.,Laboratory of Biocompatibility | Bigi A.,University of Bologna | And 5 more authors.
Biointerphases | Year: 2015

Demineralized bone matrix (DBM) is currently used in many clinical applications for bone augmentation and repair. DBM is normally characterized by the presence of bone morphogenetic proteins. In this study, the authors have optimized methods to obtain DBM under good manufacturing practice, resulting in enhanced bioactivity. The processed DBM can be used alone, together with nanostructured hydroxyapatite (nanoHA), or dispersed in a physiological carrier or hydrogel. In this study, osteoblasts (MG-63) and human bone marrow derived mesenchymal stem cells (hMSCs) were cultured on DBM pastes made in phosphate buffered saline solution or poly(N-isopropylacrylamide) (PNIPAAM) hydrogels with or without nanoHA. The authors observed that the presence of PNIPAAM reduced osteoblast adhesion, while the addition of nanoHA increased osteoblast adhesion, proliferation, interleukin-6 (IL-6) production, and reduced lactate dehydrogenase (LDH) production. Increasing concentrations of PNIPAAM in combination with nanoHA further increased osteoblast proliferation, and decreased IL-6 and LDH production. Incorporation of PNIPAAM in DBM enhanced hMSCs proliferation and collagen type-I production. Furthermore, a combination of PNIPAAM and nanoHA further increased alkaline phosphatase and osteocalcin production in hMSCs, independently from the concentration of PNIPAAM. This study shows that combinations of DBM with nanoHA and PNIPAAM seem to offer a promising route to enhance cell activity and induce osteogenic differentiation. © 2015 American Vacuum Society.


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.


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.

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