Chemical Compounds Released from Specific Osteoinductive Bioactive Materials Stimulate Human Bone Marrow Mesenchymal Stem Cell Migration.

In this work, a poly(L-lactide-co-glycolide) (PLGA)-based composite was enriched with one of the following sol-gel bioactive glasses (SBG) at 50 wt.%: A1-40 mol% SiO2, 60 mol% CaO, CaO/SiO2 ratio of 1.50; S1-80 mol% SiO2, 20 mol% CaO, CaO/SiO2 ratio of 0.25; A2-40 mol% SiO2, 54 mol% CaO, 6 mol% P2O5, CaO/SiO2 ratio of 1.35; S2-80 mol% SiO2,16 mol% CaO, 4 mol% P2O5, CaO/SiO2 ratio of 0.20. The composites and PLGA control sheets were then soaked for 24 h in culture media, and the obtained condition media (CM) were used to treat human bone marrow stromal cells (hBMSCs) for 72 h. All CMs from the composites increased ERK 1/2 activity vs. the control PLGA CM. However, expressions of cell migration-related c-Fos, osteopontin, matrix metalloproteinase-2, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and bone morphogenetic protein 2 were significantly increased only in cells treated with the CM from the A1/PLGA composite. This CM also significantly increased the rate of human BMSC migration but did not affect cell metabolic activity. These results indicate important biological markers that are upregulated by products released from the bioactive composites of a specific chemical composition, which may eventually prompt osteoprogenitor cells to colonize the bioactive material and accelerate the process of tissue regeneration.

Investigating the Anticancer Potential of Zinc and Magnesium Alloys: From Base Materials to Nanocoated Titanium Implants.

In this work, we show the in vitro anticancer potential of surgical wires, obtained from zinc (ZnMg0.004) or magnesium (MgCa0.7) alloys by spatial technology comprising casting, extrusion, and final drawing processes. We also present the selective anticancer effects of applied soluble multilayer nanocoatings of zinc and magnesium onto titanium surfaces using the pulse laser deposition method. In the latter, the titanium samples were produced via 3D printing using the selective laser melting method and coated with various combinations of zinc and magnesium layers. For cytotoxicity studies, human dental pulp-derived stem cells (hDPSCs) and human osteosarcoma SaOS-2 cell line were used as representatives of healthy and cancer cells. Cells were examined against the 0.3-3.0 cm2/mL material extract ratios obtained from experimental and steel surgical wires, the latter being the current clinical industry standard. The MgCa0.7 alloy wires were approx. 1.5 times more toxic to cancer cells at all examined extract ratios vs. the extracts from steel surgical wires that exhibited comparable toxicity towards healthy and cancer cells. The ZnMg0.004 alloy wires displayed increased toxicity towards cancer cells with decreasing extract ratios. This was also reflected in the increased anticancer effectiveness, calculated based on the viability ratio of healthy cells to cancer cells, from 1.1 to 4.0 times. Healthy cell viability remained at 80-100%, whereas cancer cell survival fluctuated at 20-75%, depending on the extract ratio. Furthermore, the culture of normal or cancer cells on the surface of Zn/Mg-coated titanium allowed us to select combinations of specific coating layers that yielded a comparable anticancer effectiveness to that observed with the experimental wires that ranged between 2 and 3. Overall, this work not only demonstrates the substantial anticancer properties of the studied wires but also indicates that similar anticancer effects can be replicated with appropriate nanocoatings on titanium samples. We believe that this work lays the groundwork for the future potential development of the category of new implants endowed with anticancer properties.

The role of CaO/SiO2 ratio and P2O5 content in gel-derived bioactive glass-polymer composites in the modulation of their bioactivity and osteoinductivity in human BMSCs.

We obtained a range of PLGA-based composites containing sol-gel bioactive glasses (SBG) from the SiO2-CaO and SiO2-CaO-P2O5 systems. Eight SBGs with different CaO/SiO2 ratios with and without P2O5 were incorporated at 50% w/w to PLGA matrix and structured into thin films suitable for cell culture. The SBG/PLGA composites were examined for their bioactivity in simulated body fluid (SBF), ion release profile in culture media with and without cells, and osteoinductivity in standard human bone marrow stromal cell (hBMSC) cultures without osteogenic growth factors. Our results indicate different surface activity of composites depending on the presence/absence of P2O5 in SBG composition. Furthermore, ion release profile to culture medium differed depending on the presence/absence of cells. Direct culture of hBMSC on the SiO2-CaO/PLGA composite films resulted in elevated Runx-2 mRNA, opposite to low Runx-2 mRNA levels on SiO2-CaO-P2O5/PLGA films. All studied composites increased Osx mRNA levels. Whereas some of SiO2-CaO/PLGA composites did not elevate BMP-2 and -6 proteins in hBMSC cultures, high levels of these BMPs were present in all cultures on SiO2-CaO-P2O5/PLGA composites. All composites induced BMP-related Tak1 signalling, whereas Smad1 signalling was restricted mostly to composites containing three-component SBGs. ALP activity of hBMSC and BMP-related luciferase activity of mouse BRITE cells differed depending on whether the cells were stimulated with culture medium conditioned with SBG/PLGA composites or the cells were directly cultured on the composite surfaces. Altogether, beyond bioactivity and osteoinductivity of SBG/PLGA composites, our studies show key differences in the biological response to both the bioactive material dissolution products and upon direct cell-material contacts.

In vitro osteogenic potential of collagen/chitosan-based hydrogels-silica particles hybrids in human bone marrow-derived mesenchymal stromal cell cultures.

The aim of this study was to assess osteogenic potential of three groups of biopolymeric hydrogel-based surfaces made of plain collagen, chitosan or collagen/chitosan, crosslinked with genipin or all three biopolymers modified with silica particles of two sizes (S1=240nm and S2=450nm). Biocompatibility and osteoinductive properties of the resulting composites were analyzed in the human bone marrow-derived mesenchymal stromal cells (hBMSCs) in vitro cultures. It was revealed that all tested materials are biocompatible and significantly enhance ALP activity in hBMSCs which was particularly pronounced for collagen/chitosan based hybrids. Gene expression (RUNX-2, COL-I, OC and VEGF mRNA) analyses performed in hBMSCs cultured at collagen/chitosan materials showed that ColChS1 hybrid the most effectively promotes osteogenic differentiation of hBMSCs. SEM and EDS analyses of materials carried out after 20days of hBMSCs culturing on ColCh-based hydrogels revealed that the hybrid materials enhanced hBMSCs-mediated mineralization of ECM. Our studies revealed that collagen/chitosan hydrogels modified with silica particles of smaller sizes (ColChS1) exhibit high pro-osteogenic properties without the need of applying any additional osteogenic inducers. That suggests that ColChS1 having the intrinsic osteoinductive activity holds great potential as material of choice for bone regeneration procedures, especially in regeneration of small bone losses.

Degradation, bioactivity, and osteogenic potential of composites made of PLGA and two different sol-gel bioactive glasses.

We have developed poly(L: -lactide-co-glycolide) (PLGA) based composites using sol-gel derived bioactive glasses (S-BG), previously described by our group, as composite components. Two different composite types were manufactured that contained either S2-high content silica S-BG, or A2-high content lime S-BG. The composites were evaluated in the form of sheets and 3D scaffolds. Sheets containing 12, 21, and 33 vol.% of each bioactive glass were characterized for mechanical properties, wettability, hydrolytic degradation, and surface bioactivity. Sheets containing A2 S-BG rapidly formed a hydroxyapatite surface layer after incubation in simulated body fluid. The incorporation of either S-BG increased the tensile strength and Young's modulus of the composites and tailored their degradation rates compared to starting compounds. Sheets and 3D scaffolds were evaluated for their ability to support growth of human bone marrow cells (BMC) and MG-63 cells, respectively. Cells were grown in non-differentiating, osteogenic or osteoclast-inducing conditions. Osteogenesis was induced with either recombinant human BMP-2 or dexamethasone, and osteoclast formation with M-CSF. BMC viability was lower at higher S-BG content, though specific ALP/cell was significantly higher on PLGA/A2-33 composites. Composites containing S2 S-BG enhanced calcification of extracellular matrix by BMC, whereas incorporation of A2 S-BG in the composites promoted osteoclast formation from BMC. MG-63 osteoblast-like cells seeded in porous scaffolds containing S2 maintained viability and secreted collagen and calcium throughout the scaffolds. Overall, the presented data show functional versatility of the composites studied and indicate their potential to design a wide variety of implant materials differing in physico-chemical properties and biological applications. We propose these sol-gel derived bioactive glass-PLGA composites may prove excellent potential orthopedic and dental biomaterials supporting bone formation and remodeling.

Gel-derived bioglass as a compound of hydroxyapatite composites.

Despite the excellent biocompatibility of hydroxyapatite and bioglass, their clinical applications are limited to non-load-bearing implants and implant coatings due to their low mechanical properties. We have developed two different composites made of hydroxyapatite (HA) and gel-derived bioglasses designated S2 (80 mol% SiO(2)-16 mol% CaO-4 mol% P(2)O(5)) or A2 (40 mol% SiO(2)-54 mol% CaO-6 mol% P(2)O(5)). We show that the combination of hydroxyapatite with either bioglass results in better composite bioactivity and biocompatibility compared to HA alone. We used a commercially available hydroxyapatite that was sintered with varying additions (10%, 50%) of A2 or S2 bioglass. Scanning electron microscopy and x-ray diffraction were used to characterize the microstructure and phases of the composites. The elastic properties of bioglass/HA composites were analyzed with the use of the pulse ultrasonic technique. The bioactivity (surface activity) of the composites was assessed by determining the changes of surface morphology and composition after soaking in simulated body fluid (SBF) for 7 and 14 days. The biocompatibility of the obtained composites was then assessed in vitro using adult human bone marrow stromal cells. Cells were seeded on the material surfaces at a density of 10(4) cells cm(-2) and cultured for 7 days in non-differentiating and osteogenic conditions. The number of live cells was estimated in both standard and osteogenic cultures, followed by alkaline phosphatase (ALP) activity assay in osteogenic cultures. We determined that 10 wt% addition of A2 (E = 12.24 GPa) and 50 wt% addition of S2 (E = 16.96 GPa) to the HA base results in higher Young's modulus of the composites compared to pure hydroxyapatite (E = 9.03 GPa). The rate of Ca-P rich layer formation is higher for bioglass/HA composites containing A2 bioglass compared to the composites containing S2 bioglass. Evaluation of cell growth on the bioglass/HA composites showed that the incorporation of either 50 wt% S2 or 50 wt% A2 into the hydroxyapatite base significantly improves cell viability when compared to cells grown on pure HA. Also the cellular activity of ALP, an early marker of osteoblasts, increases with the amount of bioglass addition to the composites.

[Revision arthroplasty in aseptic loosening of cemented sockets of hip prosthesis]. / Wymiana aseptycznie obluzowanych panewek cementowych stawu biodrowego.

The aim of this paper was to assess early results of revision arthroplasty in aseptic loosening of cemented sockets. A group of 67 patients (53 females and 14 males) age ranging from 47 to 78 years (average: 72 years) who underwent revision arthroplasty because of aseptic loosening of cemented sockets. Early surgical treatment can spare the patient from a risky procedure and lead to better end results. In cases with massive bone destruction of the pelvis good results can be achieved by using bone grafts and anti-protrusion cages.