Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy

Laboratory for, Italy

Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy

Laboratory for, Italy
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Boriani F.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | Fazio N.,Prometeo LaboratoryRizzoli Orthopaedic InstituteBologna Italy | Fotia C.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | Savarino L.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | And 4 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2017

Autografts represent the gold standard for peripheral nerve reconstruction but their limited availability, the discrepancy of nerve caliber, and long surgical times are drawbacks. Allografts have therefore become a valid alternative option. In particular, acellular nerve allografts (ANAs) rather than fresh allografts do not need immunosuppression and appear to be safe and effective based on recent studies. An innovative method was conceived to obtain ANAs, so as to speed up nerve decellularization, without compromising nerve architecture, and without breaking the asepsis chain. Several detergent-based techniques, integrated with sonication and mechanical stirring, were tested in vitro on rabbit nerves, to identify, by microscopy and immunohistochemistry, the most effective protocol in terms of cell lysis and cellular debris clearance, while maintaining nerve architecture. Furthermore, a pilot in vivo study was performed: ANAs were implanted into tibial nerve defects of three rabbits, and autografts, representing the gold standard, in other three animals. Twelve weeks postoperatively, rabbits were clinically evaluated and euthanasized; grafts were harvested and microscopically and histomorphometrically analyzed. The method proved to be effective in vitro: the treatment removed axons, myelin and cells, without altering nerve architecture. The in vivo study did not reveal any adverse effect: animals maintained normal weight and function of posterior limb during the entire experimental time. A mild fibrotic reaction was observed, macrophages and leukocytes were rare or absent; ANAs regenerated fascicles and bundles were comparable versus autografts. Based on these results, this decellularization protocol is encouraging and deserves deeper investigations with further preclinical and clinical studies. © 2017 Wiley Periodicals, Inc.


Savarino L.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | Fotia C.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | Roncuzzi L.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | Greco M.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy | Baldini N.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy
Journal of Biomedical Materials Research - Part B Applied Biomaterials | Year: 2015

Metal-on-metal hip resurfacing (MOM-HR) represents a viable alternative to traditional arthroplasty. Nevertheless, in MOM coupling both metal nanoparticles and ions are released, whose toxicity remains a matter of concern. We investigated whether 'endogenous' chronic exposure to cobalt and chromium induced a state of oxidative stress, DNA damage and a hypoxia-like response in patients with well-functioning MOM-HR. Twenty-two patients with unilateral MOM-HR were recruited at long-term. Twenty-one osteoarthritic subjects were enrolled for comparison. Serum ion levels were measured and correlated with 8-hydroxydeoxyguanosine and circulating-free-DNA, as markers of oxidative DNA damage. Moreover, the hypoxia-inducible factor-1α, marker of hypoxic state, was evaluated. Ion concentrations were found to be 5-to-15 times higher in MOM-HR patients than in presurgery subjects (p<0.001); circulating-free-DNA, 8-hydroxydeoxyguanosine, and hypoxia-inducible factor-1α levels were not significantly different between groups and did not correlate with ion levels. Analyzing the results according to gender, MOM-HR males had higher 8-hydroxydeoxyguanosine levels (p=0.01) compared with MOM-HR females. Similarly, circulating-free-DNA values were higher in males than females, even if this difference did not reach statistical significance. This research is the first that attempted to investigate the long-term effects of ion dissemination in subjects with well-fixed MOM implants. A significant correlation between biomarkers increase and ion levels was not demonstrated. Nevertheless, both circulating-free-DNA and 8-hydroxydeoxyguanosine showed a tendency to increase in MOM-HR males. Further studies with a larger sample size should be performed to detect the clinical relevance of biomarkers increase especially in younger subjects, where a chronic moderately elevated exposure has to be faced. © 2015 Wiley Periodicals, Inc.


Mazzotti A.,University of Bologna | Baldini N.,University of Bologna | Savarino L.,Laboratory for Orthopaedic Pathophysiology and Regenerative MedicineRizzoli Orthopaedic InstituteBologna Italy
Journal of Biomedical Materials Research - Part B Applied Biomaterials | Year: 2015

Ceramic-on-metal (CoM) total hip arthroplasty (THA) theoretically combines both the advantages of ceramic-on-ceramic (CoC) and metal-on-metal (MoM) bearings: negligible rupture risk of the liner with a limited ion release. As primary endpoint, we asked whether serum cobalt, chromium and molybdenum concentrations in 20 CoM-THA patients at an average of 3-years follow-up were higher than those measured in the pre-operative population and correlate with clinical/radiological parameters. As secondary endpoint, we wanted to verify whether ion levels in CoM-THA patients were different from those obtained in a similar cohort of 29 MoM-THA patients at the same average follow-up. Ion values were measured by atomic absorption spectrometry. Functional outcome was assessed with Harris Hip Score and UCLA scale. Presence of radiographic radiolucencies around the implant, and acetabular inclination angle were evaluated. Chromium and cobalt levels in CoM-THA patients were significantly higher (p<0.001) at 3-years follow-up than before surgery. Molybdenum concentrations were not significantly different (p=0.45). No signs of implant loosening were recorded. Functional outcome was excellent with HHS and UCLA scale rising from 50 and 3.6 pre-operatively to 90.8 and 6.3, respectively at 3-years follow-up (p<0.001). Chromium serum levels were significantly lower in CoM-THA than in MoM-THA group (p=0.02) while cobalt values, even if lower, did not reach statistically significance (p=0.054). Our results show that CoM-THA patients achieve excellent clinical outcome with a limited chromium release at 3-years follow-up. © 2015 Wiley Periodicals, Inc.

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