IntroductionCell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model.MethodsThe induction of OA was performed surgically through bilateral anterior cruciate ligament transection (ACLT) to achieve eight weeks from ACLT a mild grade of OA. A total of 2 × 106 and 6 × 106 autologous ASCs isolated from inguinal fat, expanded in vitro and suspended in 4% rabbit serum albumin (RSA) were delivered in the hind limbs; 4% RSA was used as the control. Local bio-distribution of the cells was verified by injecting chloro-methyl-benzamido-1,1'-dioctadecyl-3,3,3'3'-tetra-methyl-indo-carbocyanine per-chlorate (CM-Dil) labeled ASCs in the hind limbs. Cartilage and synovial histological sections were scored by Laverty's scoring system to assess the severity of the pathology. Protein expression of some extracellular matrix molecules (collagen I and II), catabolic (metalloproteinase-1 and -3) and inflammatory (tumor necrosis factor- α) markers were detected by immunohistochemistry. Assessments were carried out at 16 and 24 weeks.ResultsLabeled-ASCs were detected unexpectedly in the synovial membrane and medial meniscus but not in cartilage tissue at 3 and 20 days from ASC-treatment. Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.ConclusionsOur data reveal a healing capacity of ASCs in promoting cartilage and menisci repair and attenuating inflammatory events in synovial membrane inhibiting OA progression. On the basis of the local bio-distribution findings, the benefits obtained by ASC treatment could be due to a trophic mechanism of action by the release of growth factors and cytokines.

Micro-CT proved to be a powerful nondestructive 3D analysis tool for visualizing the porous internal microstructure of dental/endodontic materials at the interface with dentine. The proportion of voids was least in the apical third of root canals. Voids reduced over time in the presence of simulated body fluid.

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Background: Guided bone regeneration (GBR) allows to achieve vertical ridge augmentation whether with nonresorbable membranes or resorbable membranes with Ti-mesh, but till now no studies are published comparing histological and histomorphometrical outcomes of these two procedures.Materials and Methods: Forty partially edentulous patients required vertical bone regeneration to place implants in the posterior mandible: 20 patients were randomly assigned to group A (Ti-PTFE); while 20 patients to group B (Collagen plus Ti-mesh).For both groups, graft material was a 50:50 mixture of autogenous bone and bone allograft. After 9 months, tissue biopsies were taken from augmented sites (regenerated bone ROI-1; native bone ROI-2) and undergone to histological and histomorphometric analysis. Percentages of bone tissue (B.Ar), biomaterial (Mat. Ar), and soft tissue (St.Ar) were measured; measurements of perimeters were calculated too. ROI-1 values were also compared to ROI-2 in both groups.Results: Twenty-five samples were collected and analyzed consecutively: 13 in group A and 12 in group B. The mean B.Ar, Mat.Ar, and St.Ar were 39. 7%, 8.6%, and 52.1% in group A; similar results were obtained in group B, with mean values of 42.1%, 9.6%, and 48.3%, respectively. No significant statistically differences were observed.Differences were observed between ROI-1 and ROI-2 in both group. Finally, bone structure index of ROI-1 and ROI-2 showed statistical differences. Conclusions:The preliminary results of this study suggest that GBR using nonresorbable membranes and Ti-mesh with resorbable membranes in combination with autogenous bone and bone allograft provide similar histological and histomorphometric results. K E Y W O R D Sbone augmentation, bone defects, histological analysis

Bone cell response to 3D bioinspired scaffolds was tested on osteoblast culture supernatants and by means of quantitative polymerase chain reaction (qPCR). Foaming and freeze-drying method was optimized in order to obtain three-dimensional interconnected porous scaffolds of gelatin at different contents of nanocrystalline hydroxyapatite (HA). Addition of a non toxic crosslinking agent during foaming stabilized the scaffolds, as confirmed by the slow and relatively low gelatin release in phosphate buffer up to 28 days. Micro-computed tomography reconstructed images showed porous interconnected structures, with interconnected pores displaying average diameter ranging from about 158 to about 71 μm as the inorganic phase content increases from 0 to 50 wt %. The high values of connectivity (>99%), porosity (> 60%), and percentage of pores with a size in the range 100-300 μm (>50%) were maintained up to 30 wt % HA, whereas higher content provoked a reduction of these parameters, as well as of the average pore size, and a significant increase of the compressive modulus and collapse strength up to 8 ± 1 and 0.9 ± 0.2 MPa, respectively. Osteoblast cultured on the scaffolds showed good adhesion, proliferation and differentiation. The presence of HA promoted ALP activity, TGF-β1, and osteocalcin production, in agreement with the observed upregulation of ALP, OC, Runx2, and TGF-β1 gene in qPCR analysis, indicating that the composite scaffolds enhanced osteoblast activation and extra-cellular matrix mineralization processes.

Bone metastases impair general health status, quality of life and survival of patients. Electrochemotherapy (ECT), which combines electroporation (EP) and the administration of anticancer drugs, has been recently introduced into clinical practice for the local treatment of solid tumours. In the present study, the ability of EP with bleomycin (Bleo) to induce MRMT-1 rat breast cancer cell death was investigated in vitro. Then, an in vivo model for bone metastases was set up by the inoculation of MRMT-1 cells in rat proximal tibia. 7 days after tumour induction the animals were treated with Bleo, EP, Bleo followed by EP (ECT), or left untreated. ECT eliminated the tumour in 6 out of 8 (75 %) treated metastases. Radiological evaluation showed that the Honore score in ECT-treated animals was significantly lower when compared with the other groups (p < 0.0005) and not significantly different from healthy controls. Bone morphology in ECT-treated animals, evaluated by histological and microtomographical analyses, showed intact cortical and trabecular bone structure with new bone apposition. Histomorphometric evaluation showed that ECT-treated metastases had significantly higher bone volume, trabecular number, trabecular thickness and bone mineral density compared with those of untreated metastases (respectively p < 0.0005 for BV/TV, Tb.N and BMD; p < 0.05 for Tb.Th) or metastases treated with Bleo (p < 0.05 for BV/TV, Tb.N, p < 0.005 for BMD) or EP (p < 0.005 for BV/TV, Tb.N; p < 0.0005 for BMD). These findings suggest that early ECT treatment of bone metastases is minimally invasive, safe and effective, thus providing pre-clinical evidence for its use in the treatment of human bone metastases.

Current therapeutic strategies for osteochondral restoration showed a limited regenerative potential. In fact, to promote the growth of articular cartilage and subchondral bone is a real challenge, due to the different functional and anatomical properties. To this purpose, alginate is a promising biomaterial for a scaffold-based approach, claiming optimal biocompatibility and good chondrogenic potential. A previously developed mineralized alginate scaffold was investigated in terms of the ability to support osteochondral regeneration both in a large and medium size animal model. The results were evaluated macroscopically and by microtomography, histology, histomorphometry, and immunohistochemical analysis. No evidence of adverse or inflammatory reactions was observed in both models, but limited subchondral bone formation was present, together with a slow scaffold resorption time.The implantation of this biphasic alginate scaffold provided partial osteochondral regeneration in the animal model. Further studies are needed to evaluate possible improvement in terms of osteochondral tissue regeneration for this biomaterial.