Age and synovitis affect the results of the treatment of knee osteoarthritis with Microfragmented Autologous Fat Tissue.

PURPOSE: This study aims to assess the effectiveness of Microfragmented Autologous Fat Tissue (MFAT) treatment for knee osteoarthritis and to investigate whether patients' pre-treatment clinical condition, such as synovitis, correlates with clinical outcomes, to identify potential predicting factors for the success or failure of the treatment. METHODS: In this prospective Cohort Study Level II multicentric trial, consecutive patients with a diagnosis of early/mild osteoarthritis and failure of previous conservative measures were enrolled to undergo diagnostic arthroscopy and a single MFAT injection. Patients were assessed with repeated scoring systems at baseline, 6 months, and 12 months after surgery. The demographic features, the arthroscopic findings, the immunophenotype of injected tissue and the histologic examination of synovia of failed patients were analyzed. RESULTS: Data from 91 patients showed a significant improvement in Lysholm, WOMAC scores at 1-year follow-up (p < 0.001). A significant decrease in VAS score was observed, while a significant improvement of measured flexion angle was registered at 1 year (p < 0.001). No major complications were reported. Age and synovitis were identified as significant factors influencing the clinical outcome (p < 0.05). Body mass index, previous or concomitant procedures, and specific cartilage defects had no influence. The mean number of injected adipose tissue-derived mesenchymal stem cells seem not to correlate with the clinical outcome. CONCLUSION: MFAT is effective in reducing pain when used with a single dose injection in early/mild OA of the knee, without major complications. Age over 60 and synovitis may be predictive for persistent pain at one year and should be considered before indications.

Proanthocyanidin may improve the shear bond strength at the composites/dentine interface.

TThis study aimed at assessing whether proanthocyanidin, a collagen cross-linker, affects the adhesion strength of resin composites on the dentine surface. Freshly extracted, caries-free, human molars (N=55) were embedded in transparent resin and bisected. The halves were then assigned to either a treated or a non-treated group, where the treatment consisted of a 10 min incubation in a 6.5% proanthocyanidin solution in PBS. A resin composite cylinder was polymerized perpendicularly to the dentinal surfaces and shear tests were made, using an Instron-like machine. The fracture surfaces were characterized by optical (Picro-Sirius Red stain) and electron microscopy (FESEM EDX analysis). Mean bond strength values were 10.73 MPa (SD 3.70) for the treated group and 8.69 MPa (SD 3.20) for the non-treated group (p less than 0.05 Student’s t-test). No constant fracture patterns could be found within the two groups. Proanthocyanidin treatment may improve the adhesion properties of the dentine-bonding interface.

Cytokine, Chemokine, and Growth Factor Profile Characterization of Undifferentiated and Osteoinduced Human Adipose-Derived Stem Cells.

Bone is the second most manipulated tissue after blood. Adipose-derived stem cells (ASCs) may become a convenient source of MSC for bone regenerative protocols. Surprisingly, little is known about the most significant biomolecules these cells produce and release after being osteoinduced. Therefore, the present study aimed at dosing 13 candidates chosen among the most representative cytokines, chemokines, and growth factors within the conditioned media of osteodifferentiated and undifferentiated ASCs. Two acknowledged osteoblastic cell models, that is, MG-63 and SaOs-2 cells, were compared. Notably, IL-6, IL-8, MCP-1, and VEGF were highly produced and detectable in ASCs. In addition, while IL-6 and IL-8 seemed to be significantly induced by the osteogenic medium, no such effect was seen for MCP-1 and VEGF. Overall SaOS-2 had a poor expression profile, which may be consistent with the more differentiated phenotype of SaOs-2 compared to ASCs and MG-63. Instead, in maintaining medium, MG-63 displayed a very rich production of IL-12, MCP-1, IP-10, and VEGF, which were significantly reduced in osteogenic conditions, with the only exception of MCP-1. The high expression of MCP-1 and VEGF, even after the osteogenic commitment, may support the usage of ASCs in bone regenerative protocols by recruiting both osteoblasts and osteoclasts of the host.

Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions.

Plasma of Argon Affects the Earliest Biological Response of Different Implant Surfaces: An In Vitro Comparative Study.

The aim of this in vitro study was to evaluate the early cell response and protein adsorption elicited by the argon plasma treatment of different commercially available titanium surfaces via a chair-side device. Sterile disks made of grade 4 titanium (n= 450, 4-mm diameter) with 3 surface topographies (machined, plasma sprayed, and zirconia blasted and acid etched) were allocated to receive 4 testing treatments (2% and 10% protein adsorption and cell adhesion with MC3T3-E1 and MG-63). Furthermore, the specimens were divided to undergo 1) argon plasma treatment (10 W, 1 bar for 12 min) in a plasma reactor, 2) ultraviolet (UV) light treatment for 2 h (positive control group), or 3) no treatment (control group). Pretreatment surface analyses based on a scanning electron microscope and profilometer images were also performed. Profilometric analysis demonstrated that the evaluated specimens perfectly suit the standard parameters. The use of argon plasma was capable of affecting the quantity of proteins adsorbed on the different surfaces, notwithstanding their roughness or topographic features at a low fetal bovine serum concentration (2%). UV light treatment for 2 h attained similar results. Moreover, both the plasma of argon and the UV light demonstrated a significant increase in the number of osteoblasts adherent at 10 min in all tested surfaces. Within its limitations, this in vitro study highlights the potential biological benefits of treating implant surfaces with plasma of argon or UV, irrespective of the roughness of the titanium surface. However, in vivo experiments are needed to confirm these preliminary data and settle the rationale of a treatment that might be clinically relevant in case of bone-reparative deficiencies.

Overcoming physical constraints in bone engineering: 'the importance of being vascularized'.

Bone plays several physiological functions and is the second most commonly transplanted tissue after blood. Since the treatment of large bone defects is still unsatisfactory, researchers have endeavoured to obtain scaffolds able to release growth and differentiation factors for mesenchymal stem cells, osteoblasts and endothelial cells in order to obtain faster mineralization and prompt a reliable vascularization. Nowadays, the application of osteoblastic cultures spans from cell physiology and pharmacology to cytocompatibility measurement and osteogenic potential evaluation of novel biomaterials. To overcome the simple traditional monocultures in vitro, co-cultures of osteogenic and vasculogenic precursors were introduced with very interesting results. Increasingly complex culture systems have been developed, where cells are seeded on proper scaffolds and stimulated so as to mimic the physiological conditions more accurately. These bioreactors aim at enabling bone regeneration by incorporating different cells types into bio-inspired materials within a surveilled habitat. This review is focused on the most recent developments in the organomimetic cultures of osteoblasts and vascular endothelial cells for bone tissue engineering.

Alumina-zirconia composites functionalized with laminin-1 and laminin-5 for dentistry: effect of protein adsorption on cellular response.

The present paper describes a study on laminin interaction with the surface of two alumina-zirconia composites with different percentages of ZrO2, both with submicrometric grain size. As major molecules within the basement membrane (BM), laminins are important protein fragments for epithelial cell adhesion and migration. On the other hand, alumina-zirconia composites are very attractive materials for dental applications due to their esthetic and mechanical properties. X-Ray photoelectron spectroscopy and atomic force microscopy were used to study the adsorption of two types of laminin, laminin-1 (Ln-1) and laminin-5 (Ln-5), onto the ceramics surfaces. The in vitro cell response was determined by intracellular phosphorylation of major kinases. Ceramics samples functionalized with laminins showed better cellular activation than untreated specimens; furthermore, cellular activation was found to be greater for the composite with higher percentage in zirconia when functionalized with Ln-5, whereas the adsorption of Ln-1 resulted in a greater activation for the alumina-rich oxide.

Healing properties of implants inserted concomitantly with anorganic bovine bone. A histomorphometric human study.

BACKGROUND: The present prospective, randomized, double-blind study evaluated the bone-forming process around implants inserted simultaneously with anorganic bovine bone (ABB) in sinus grafting. METHODS: A total of 18 threaded mini-implants with Osseotite (O) and Nanotite (N) surfaces were placed in seven patients (nine sites). After 12 months, the implants were retrieved and processed for histological analysis. A total of 18 cutting and grinding sections were investigated with bright-field light microscopy, circularly polarized light microscopy (CPLM), confocal scanning laser microscope (CSLM), and scanning electron microscope (SEM) with energy dispersive spectrometer (EDS). RESULTS: The bone-to-implant contact rate in native crestal bone was 62.6 ± 0.4% for N implants and 54.3 ± 0.5% for the O implants (p = 0.001). The collagen fibre density, as assessed by CPLM, was 79.8 ± 6.0 nm for the N group and 74.6 ± 4.6 nm for the O group (p < 0.05). Line scan EDS starting from ABB to newly formed bone showed a decrease in calcium content and an increase of carbon while phosphorus content was constant. CONCLUSIONS: While the N surface improved the peri-implant endosseous healing properties in the native bone, when compared to the O surface, it did not improve the healing properties in the bone-graft area.

Biological components in a standardized derivative of bovine colostrum.

Products of different origin, time of collection, and activities fall under the general term of colostrum and, therefore, great variability in composition as well as in the concentration of its components has been reported in the literature. In the present study, we describe the standardization of a bovine colostrum derivative and the characterization of its bioactive components. Evaluation of the most representative agents (lactoferrin, transferrin, IL-2, IFN-γ, tumor necrosis factor, IgG, and IgA) showed that a marked decrease in active components occurs after the first few hours. Bovine colostrum was, therefore, collected up to the fifth hour after delivery from Holstein cows, in the presence of preservatives, and immediately frozen. A protocol of centrifugation, filtration, and lyophilization was then applied to pools of colostrum from at least 30 cows to obtain a stable, sterile, standardized product. Preservatives were removed by dialysis. Evaluation of the active biological components of colostrum showed that the final product of colostrums contained significant and reproducible amounts of bioactive factors, including cytokines, immunomodulating factors, growth factors, and immunoglobulins. The final product appeared, therefore, as a sterile, pyrogen-free, standardized derivative of bovine colostrum with a high concentration of bioactive components.