Improved Biocompatibility Properties Research Articles

DMP1 and IFITM5 Regulate Osteogenic Differentiation of MC3T3-E1 on PEO-Treated Ti-6Al-4V-Ca2+/Pi surface.

Despite numerous studies on various surface modifications on titanium and its alloys, it remains unclear what kind of titanium-based surface modifications are capable of controlling cell activity. This study aimed to understand the mechanism at the cellular and molecular levels and investigate the in vitro response of osteoblastic MC3T3-E1 cultured on the Ti-6Al-4V surface modified by plasma electrolytic oxidation (PEO) treatment. A Ti-6Al-4V surface was prepared by PEO at 180, 280, and 380 V for 3 or 10 min in an electrolyte containing Ca2+/Pi ions. Our results showed that PEO-treated Ti-6Al-4V-Ca2+/Pi surfaces enhanced the cell attachment and differentiation of MC3T3-E1 compared to the untreated Ti-6Al-4V control but did not affect cytotoxicity as shown by cell proliferation and cell death. Interestingly, on the Ti-6Al-4V-Ca2+/Pi surface treated by PEO at 280 V for 3 or 10 min, MC3T3-E1 showed a higher initial adhesion and mineralization. In addition, the alkaline phosphatase (ALP) activity significantly increased in MC3T3-E1 on the PEO-treated Ti-6Al-4V-Ca2+/Pi (280 V for 3 or 10 min). In RNA-seq analysis, the expression of dentin matrix protein 1 (DMP1), sortilin 1 (Sort1), signal-induced proliferation-associated 1 like 2 (SIPA1L2), and interferon-induced transmembrane protein 5 (IFITM5) was induced during the osteogenic differentiation of MC3T3-E1 on the PEO-treated Ti-6Al-4V-Ca2+/Pi. DMP1 and IFITM5 silencing decreased the expression of bone differentiation-related mRNAs and proteins and ALP activity in MC3T3-E1. These results suggest that the PEO-treated Ti-6Al-4V-Ca2+/Pi surface induces osteoblast differentiation by regulating the expression of DMP1 and IFITM5. Therefore, surface microstructure modification through PEO coatings with Ca2+/Pi ions could be used as a valuable method to improve biocompatibility properties of titanium alloys.

Influence of precursor deficiency sites for borate incorporation on the structural and biological properties of boronated hydroxyapatite

The biological properties of hydroxyapatite (HA) are significantly influenced by its compositional characteristics especially doping elements and/or Ca/P ratio, which can be altered by precursor chemistry. In this study, a group of boronated (B-incorporated) hydroxyapatite (BHA) was synthesized using a precipitation method by setting the Ca/P ratio to the stoichiometric value of HA (1.67), while altering the precursor chemistry by adjusting either (Ca + B)/P (Ca-deficient precursor, BC) or Ca/(P + B) (P-deficient precursor, BP). After heat-treatment, the partial decomposition of the BC was observed, forming tricalcium phosphate as the byproduct, however, the BP showed phase stability at all temperatures. The B-ionic species in the form of (BO2)− and (BO3)3− were incorporated into the HA structure at the (PO4)3− and (OH)− positions, respectively. The incorporation of the B species also facilitated the incorporation of (CO3)2− groups specifically in the BPs. This is the first finding on BHA reporting that preferential (CO3)2− incorporation depends on the precursor chemistry used. As a result, osteoblast adhesion was superior on the BPs compared to pure HA owing to the carbonated structure, increasing cell spreading area. As such, this in vitro study highlighted that the present P-deficient precursor approach for synthesizing BHA improved biocompatibility properties and should, thus, be further considered for the next-generation of improved orthopedic applications.

Surface modification of Ti6Al4V by nanosecond laser ablation for biomedical applications

This paper presents the surface textured process of biometal Ti6Al4V by means of 355 nm Nd:YVO4 nanosecond laser. Our target is to create structures with sizes which favour osseointegration. In this work a pattern of parallel grooves was generated after a deep analysis of the irradiation parameters involved. Ablation modifies not only the topography but also physico-chemical properties of the metal surface. Changes in the morphology and the physico-chemical state of the laser induced groove pattern were studied by a scanning electron microscopy, X-ray diffraction and X- ray photoelectron spectroscopy, which revealed, among others, an increase of micro roughness and a oxide layer entirely formed by TiO2, which can improve biocompatibility properties of the textured surface.

Metallic Biomaterials Processing Technologies in Order to Obtain a New Design for a Hip Prosthesis Femoral Component

The paper presents the processing technology that could be used in order to obtain a new design of a stem component for a hip prosthesis type lattice beam. This new design was made based on the analysis of the currently successful stems used in clinical practice and on different biomechanical and biomaterials criteria. Metallic biomaterials used for manufacturing different components for hip prosthesis are usually austenitic stainless steel type 316L, Co-Cr alloy and titanium based alloy. In our study, considering the specific design of the stem, stainless steel type 316L with the nominal compositions (%weight): C <0.03, Cr 17, Ni 14.5, Mo 2.7, Mn <2.0, Si <1.0, P <0.025, S <0.010, Fe balance is used. Different mechanical processing techniques were used in order to obtain the experimental prototype. According to the well-known limitation of the stainless steel type 316L as biomaterial for long term implants, we propose for the new stem component to use a TiN coating obtained using magnetron sputtering technique. The cytotoxicity studies were performed using a CCl 81 (VERO) stabilized cellular line, in order to analyse the biocompatibility properties. The samples were examined for the development of the cellular culture, in order to compare the results obtained using direct contact method. From the point of view of these tests, it was not observed an essential modification of cells and the cellular morphology is not affected by the presence of the TiN coated metallic samples. In the conclusion, the new geometry proposed for a stem component of cemented hip prosthesis could be made using different mechanical processing techniques and appears to be a potential solution in order to solve the problems related to the stability of the total hip prosthesis, with improved biocompatibility properties due to the TiN coatings.

P-Glycoprotein Silencing with siRNA Delivered by Dope-Modified Pei Overcomes Doxorubicin Resistance in Breast Cancer Cells

Multidrug resistance (MDR) mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem, limiting successful chemotherapy of breast cancer. The use of siRNA to inhibit P-gp expression in MDR tumors is an attractive strategy to improve the effectiveness of anticancer drugs. We have synthesized a novel conjugate between a phospholipid (dioleoylphosphatidylethanolamine) and polyethylenimine (PEI) for siRNA delivery, for the purpose of silencing P-gp to overcome doxorubicin resistance in MCF-7 human breast cancer cells. The dioleoylphosphatidylethanolamine-PEI conjugate enhanced the transfection efficacy of low-molecular-weight PEI, which was otherwise totally ineffective. In addition, the polyethylene glycol/lipid coating of the new complexes gave rise to small micelle-like nanoparticles with improved biocompatibility properties. Both coated and noncoated formulations delivered P-gp-specific siRNA to MDR cells. The combination of doxorubicin and P-gp silencing formulations led to a twofold increase of doxorubicin uptake and a significant improvement of the therapeutic effect of doxorubicin in resistant cells.

Preparation of enhanced three-dimensional porous chitosan scaffolds by acetylation and aqueous extraction

We have devised a method to prepare a 3-dimensional (3D) porous acetylated chitosan scaffold for use as a cell adhesion matrix in tissue engineering applications. The scaffold was prepared by molding a mixture of chitosan and gelatin (as porogen), then removing the uncomplexed porogen by aqueous extraction from the freeze-dried material prior to acetylation. The extent of chitosan acetylation according to the reaction time was observed by X-ray diffraction (XRD) analysis. The differences between the aqueous-extracted and control phase-separated chitosan scaffolds in terms of pore morphology and interconnectivity were examined by scanning electron microscopy (SEM), enzymatic degradation, and surface roughness tests. The fibroblast cell line NIH-3T3 was used to test relative cell affinities for the acetylated versus untreated (control) chitosan scaffolds. The acetylated 3D porous scaffolds showed high interconnectivity and improved biocompatibility properties. Thus, these scaffolds may be very useful for a variety of tissue engineering applications.

In vitro biocompatibility evaluation of a novel bicarbonate-buffered amino-acid solution for peritoneal dialysis.

Conventional lactate-buffered peritoneal dialysis fluids containing glucose as the osmotic agent have been shown to compromise important peritoneal host defence functions. The current study employed an in vitro model using activated peripheral blood mononuclear leukocytes (PBMC) for the preclinical biocompatibility assessment of a novel bicarbonate-buffered peritoneal dialysis fluid containing 1.0% amino acids as the osmotic agent. PBMC (5 x 10(6)/ml) were pre-exposed (10-30 mm, 37 degrees C) to bicarbonate-buffered 1% amino-acid solution, bicarbonate- or lactate-buffered 1.5% glucose fluid, or control medium (RPMI). The cells were then washed and stimulated for 2 h at 37 degrees C in RPMI containing 100 ng/ml E.coli endotoxin from strain O55:B5. The cytokines IL-6 and TNF alpha in cell supernatants were assessed using specific enzyme immunoassays, cytokine mRNA expression by reverse transcription polymerase chain reaction. Short, i.e. 10 min, exposure to conventional, lactate-buffered glucose fluid resulted in a significant and time-dependent inhibition of cytokine release and mRNA expression by activated PBMC, whereas the cytokine response was improved even following prolonged (up to 2 h) exposure to bicarbonate-buffered 1% amino-acid solution or bicarbonate-buffered 1.5% glucose fluid. Our results suggest that very short, i.e. potentially clinically relevant, exposure to conventional dialysis fluid impairs the cytokine response by activated leukocytes. In this respect, the use of bicarbonate-buffered solutions containing 1.0% amino acids or 1.5% glucose may result in improved biocompatibility properties.