HA Matrix Research Articles

Enhanced biomedical potential of polyurethane/hydroxyapatite composites through chemical modification: A comprehensive study on structure, morphology, and cytocompatibility for tissue regeneration.

Polyurethane/hydroxyapatite (PU/HA) composites are well-known for various biomedical applications. This study reports a chemical approach to improve the interaction between HA and PU matrix. HA was surface-modified with 1,6-hexamethylene diisocyanate (HMDI). First, an isocyanate-modified HA (IHA) was synthesized by hydro-thermal method. Second, IHA was incorporated into a separately synthesized thermoplastic PU by a solvent casting technique. A series of PU/IHA composites was prepared by varying PU᾿s soft and hard segments. The IHA was added to PU (5 and 10 %). The FTIR spectra exhibited characteristic bands of urethane and HA, confirming the synthesis of the composites. XRD study showed the crystallite size of IHA (20 Å) with hexagonal geometry and an amorphous to semicrystalline nature of composites. SEM showed that composites displayed porous and granular morphology. The TGA thermograms of the composites revealed the thermal stability up to 400 °C. The IHA addition considerably improved hydrophilicity and degradation of the composites in simulated body fluid (SBF). MTT assay revealed improved cytocompatibility (> 80 %) of the composites. These results demonstrated an appreciable improvement in structure, morphology, hydrophilicity, degradation, and cytocompatibility of PU/IHA composites by chemical modification of HA. Hence, these composites possess remarkable potential for biomedical applications such as tissue regeneration.

Sulfonated Bovine Serum Albumin Hydrogel for Anti-inflammatory Treatment of Rheumatoid Arthritis via Restoring Macrophage Phenotype

Rheumatoid arthritis (RA) is an autoimmune disease with high rates of late-stage disability. Unfortunately, effective treatments for RA are limited by side-effects and high cost of clinical drugs. Bovine serum albumin (BSA) with high biocompatibility and low cost is widely used as the carrier for drug delivery. Here, sulfonated BSA (sBSA) was first time synthesized and its hydrogel system with HA matrix (sBSA/HA) was prepared for RA treatment. In RAW 264.7 cells, sBSA, but not bare BSA, significantly reduced the generation of reactive oxygen species and pro-inflammatory cytokines induced by LPS to the normal levels or even below. The scavenger receptor on macrophages was identified responsible for the enhanced uptake of sulfonated BSA. In vivo, 3% sBSA/HA showed the abilities of anti-inflammation, bone protection and restoring clinical scores and claw thickness of healthy rats in collagen-induced arthritis (CIA). Compared with the positive control (methotrexate), sBSA/HA had significant advantages in terms of speed of action, treatment effectiveness, and duration. Notably, both sBSA and sBSA/HA promoted M2 polarization (P＜0.001) by reducing the M1(CD86)/M2(CD206) phenotype ratio, suggesting the possible immune-modulation mechanism of sBSA in treating RA. Conclusively, sBSA was verified as a promising candidate for RA treatment.

Study of the Dynamics of Diflunisal Release from a Polymer Matrix

Introduction. The effectiveness of diflunisal in the treatment of cardiac amyloidosis has been clinically proven. Currently, only tablet forms of diflunisal are registered in the world, however, long-term use of NSAIDs leads to characteristic side effects. Therefore, delivery systems for diflunisal (including a form for external use) are now being actively developed to reduce side effects and improve its bioavailability.Aim. Research of the dynamics of release of the active substance diflunisal from the polymer matrix of hyaluronic acid.Materials and methods. The objects of the study are diflunisal gels in hyaluronic acid with a concentration of the main substance of 0.093, 0.14, 0.19 and 0.25 %. Quantitative determination was carried out by reverse-phase HPLC using a Prontosil C18, 120-5, 75 × 2 mm chromatographic column, thermostatically controlled at 40 °C. Eluent: phosphate buffer solution (PBS) with pH 3.0 and acetonitrile (30 : 70), flow rate 0.1 ml/min. Eluates were detected at wavelengths of 230, 270, 310 nm.Results and discussion. During the work, a method (HPLC) was selected and a method for determining diflunisal in a HA matrix was developed. The delivery system under study significantly increases the solubility of diflunisal in an aqueous solution compared to the dissolution of the substance. The release of the active substance from the matrices was carried out in a phosphate buffer solution with pH 7.6. The release rate for all samples exceeded 90 % after 3 hours after the start of the experiment, with most of the active substance released within an hour.Conclusion. The data obtained suggest that the release profile is characteristic of biodegradable matrices and diffusion-controlled delivery systems. Complete extraction of diflunisal from HA was achieved using PBS with pH 7.6 as a dissolution medium.

Green synthesis of graphene-hydroxyapatite nanocomposites with improved mechanical properties for bone implant materials

Herein, an in-situ synthesis of reduced graphene oxide-hydroxyapatite (RGO-HA) nanocomposites via a green reduction protocol is presented. 0.5, 1.0, and 1.5 wt% of RGO in HA are obtained by reducing the precursor solution with custard apple leaf extract. The 10x5 mm-sized discs of the RGO-HA nanocomposites are prepared and investigated for their mechanical properties. The presence of graphene in the composites is confirmed by UV–Visible, Raman spectroscopic techniques while XRD spectral analysis confirmed the α-tricalcium phosphate (TCP, JCPDS PDF No 00-009-0432) structure of HA. Nanoindentation and Vicker indentation studies revealed the enhancement in the mechanical properties of RGO-HA nanocomposites: elastic modulus, microhardness, and fracture toughness values are enhanced by 100%, 33.3%, and 64.5 %respectively for 1.5 wt% of graphene in HA matrix. The FE SEM analysis of the indentation cracks revealed that the wrapped and tucked graphene sheets in the HA matrix have hindered the propagation of the crack through pull-out, ridge growth, bridging, and deflection mechanisms. Nano scratch analysis revealed the enhanced surface roughness (120%) and coefficient of friction (102%) for 1.5 wt% composites than pure HA. The same composite showed 100% viability of HEK 293 cells at 12.5 μg/mL concentration and in vitro apatite mineralization when immersed for 7 days under SBF solution.

The effect of ZnO nanoparticles on nanomechanical behavior of Hydroxyapatite electrodeposited on NiTi biomedical alloy

This paper aims at surface characterization, chemical composition, and mechanical properties of Hydroxyapatite/ZnO (HA/ZnO) nanocomposite coatings on NiTi biomedical alloy. Morphological observations by FESEM and AFM techniques showed that ZnO NPs were responsible for a uniform, porous HA matrix. XRD analysis proved the pure HA phase synthesis in the presence of ZnO NPs; without them, there were other secondary CaP phases. XPS chemical state investigations firmly confirmed the presence of ZnO NPs by showing peaks at 531.05 eV (O ─ Zn bond) and 1021.82 eV (Zn ─ O bond). Nano-hardness test highlighted a significant enhancement in hardness of composite coating (0.37 GPa) compared to pure HA coating (0.19 GPa). The notable point was that HA/ZnO nanocomposite exhibited more plasticity than HA simple coating. This is beneficial as it provides a comfortable spot for cellular activities. Last but not least, the nano-scratch analysis revealed a great effect of ZnO inclusion on reducing friction coefficient by around 40%. The critical load was also much higher for HA/ZnO composite coating (91.4 mN) than HA coating (58.5 mN). Owing to higher plasticity and lower friction coefficient, HA/ZnO composite managed to ease the movement of the indenter tip on its surface, thereby suffering less shear stress.

Hyaluronan supports the limbal stem cell phenotype during ex vivo culture

BackgroundHyaluronan (HA) has previously been identified as an integral component of the limbal stem cell niche in vivo. In this study, we investigated whether a similar HA matrix is also expressed in vitro providing a niche supporting limbal epithelial stem cells (LESCs) during ex vivo expansion. We also investigated whether providing exogenous HA in vitro is beneficial to LESCs during ex vivo expansion.MethodHuman LESCs (hLESCs) were isolated from donor corneas and a mouse corneal epithelial progenitor cell line (TKE2) was obtained. The HA matrix was identified surrounding LESCs in vitro using immunocytochemistry, flow cytometry and red blood exclusion assay. Thereafter, LESCs were maintained on HA coated dishes or in the presence of HA supplemented in the media, and viability, proliferation, cell size, colony formation capabilities and expression of putative stem cell markers were compared with cells maintained on commonly used coated dishes.ResultshLESCs and TKE2 cells express an HA-rich matrix in vitro, and this matrix is essential for maintaining LESCs. Further supplying exogenous HA, as a substrate and supplemented to the media, increases LESC proliferation, colony formation capabilities and the expression levels of putative limbal stem cell markers.ConclusionOur data show that both exogenous and endogenous HA help to maintain the LESC phenotype. Exogenous HA provides improved culture conditions for LESC during ex vivo expansion. Thus, HA forms a favorable microenvironment for LESCs during ex vivo expansion and, therefore, could be considered as an easy and cost-effective substrate and/or supplement for culturing LESCs in the clinic.

Calcium Phosphate/Hyaluronic Acid Composite Hydrogels for Local Antiosteoporotic Drug Delivery.

Despite the bone ability of self-regeneration, large bone defects require surgical intervention. Likewise, when it comes to osteoporotic bone fractures, new approaches should be considered a supportive mechanism for the surgery. In recent years, more and more attention has been attracted to advanced drug delivery systems for local osteoporosis treatment, combining appropriate biomaterials with antiosteoporotic drugs, allowing simultaneously to regenerate the bone and locally treat the osteoporosis. Within the current research, hyaluronic acid/strontium ranelate (HA/SrRan), HA/calcium phosphate nanoparticles (HA/CaP NPs), and HA/CaP NPs/SrRan hydrogels were prepared. The effect of CaP and SrRan presence in the composites on the swelling behavior, gel fraction, molecular structure, microstructure, and SrRan and Sr2+ release, as well as in vitro cell viability was evaluated. Obtained results revealed that the route of CaP nanoparticle incorporation into the HA matrix had a significant effect on the hydrogel gel fraction, rheological properties, swelling behavior, and microstructure. Nevertheless, it had a negligible effect on the release kinetics of SrRan and Sr2+. The highest cell (3T3) viability (>80%) was observed for HA hydrogels, with and without SrRan. Moreover, the positive effect of SrRan on 3T3 cells was also demonstrated, showing a significant increase (up to 50%) in cell viability if the used concentrations of SrRan were in the range of 0.05–0.2 μg/ml.

Novel 8%‐TiO2‐nanoparticle‐reinforced dense polycrystalline bovine hydroxyapatite bioceramic

AbstractThis study aimed to produce and characterize the microstructure and mechanical properties of dense polycrystalline bovine hydroxyapatite (DPBHA) bioceramics with 5% and 8% of TiO2 nanoparticles after final synthetization for future use in dental implants. Structural characterization was obtained from analyzes by Fourier transform infrared spectroscopy, X‐ray diffraction, scanning electron microscope, energy dispersive spectroscopy, and relative density and apparent porosity. The mechanical characterization was performed by measuring the fracture toughness after three‐point flexural strength (FS) test. The microstructural characterization results showed no secondary phase formation and nonhomogeneous nanoparticle dispersion in HA matrix. DPBHA/Np8% (2.9 ± 0.09 g/cm3) exhibited significantly greater density than DPBHA (2.7 ± 0.03 g/cm3) (p = 0.011) and DPBHA/Np5% (2.7 ± 0.05 g/cm3) (p = 0.041). DPBHA (0.9%) had the smallest porosity followed by DPBHA/Np8% (3.4%). DPBHA/Np5% (4.5%) exhibited the greatest proportion of pores. Pure HA (51.7 ± 10.3 MPa) and DPBHA/Np8% (47.4 ± 6.4 MPa) had significant greater FS (p < 0.001) than DPBHA/Np5% (28.8 ± 3.1 MPa). DPBHA (0.43 ± 0.01 MPa m1/2) and DPBHA/Np8% (0.40 ± 0.06 MPa m1/2) presented greater KIc than DPBHA/Np5% (0.23 ± 0.02 MPa m1/2) (p < 0.003; p < 0.007). In conclusion, 8% TiO2 nanoparticle addition to this synthesis would be a promising HA blend, as mechanical properties were similar, and the relative density/apparent porosity showed superior results than those of the DPBHA.

Preparation of carbon fiber/Mg-doped nano-hydroxyapatite composites under low temperature by pressureless sintering

In order to protect carbon fibers (CF) from oxidation damage during sintering process, rod-like Mg-doped nano-hydroxyapatite (Mg-nHA) with an increased thermal decomposition temperature and reduced sintering temperature was synthesized by hydrothermal method. The synthesized bone-like Mg-nHA with similar composition and morphology to bone apatite was used as the matrix to prepare CF reinforced Mg-nHA composites (CF/Mg-nHA) at a low temperature of 700 °C by pressureless sintering. The increase of temperature slightly influenced the growth of Mg-nHA prepared by hydrothermal method from 160 °C to 200 °C. The Mg-nHA were short and rod-like in structure with a length of approximate 100 nm. When doping 1% magnesium, the decomposition temperature of Mg-nHA increased by 100 °C compared with that of nHA. This can protect CF from oxidation damage which is often encountered when sintering CF reinforced hydroxyapatite composites at high temperature and enhance reinforcing effects of CF. The bending strength of CF/Mg-nHA with 1 wt% CF was 8.51 MPa, which increased by 19.5% compared with Mg-nHA. Alternatively, the rod-like Mg-nHA was prepared on the surface of CF by electrochemical deposition and Mg-nHA coated CF was used to reinforce Mg-nHA, the coefficient of thermal expansion mismatch between CF and HA matrix could be mitigated. The compressive strength of Mg-nHA coated CF reinforced Mg-nHA (CF/Mg-nHA/Mg-nHA) composites with 0.5% CF sintered at 800 °C were 41.3 ± 1.56 MPa, which was attributed to the improved strengthening effect of CF and the good interface between CF and Mg-nHA matrix.

Impact Evaluation of High Energy Ball Milling Homogenization Process in the Phase Distribution of Hydroxyapatite-Barium Titanate Plasma Spray Biocoating

Air plasma spray technique (APS) is widely used in the biomedical industry for the development of HA-based biocoatings. The present study focuses on the influence of powder homogenization treatment by high-energy ball milling (HEBM) in developing a novel hydroxyapatite-barium titanate (HA/BT) composite coating deposited by APS; in order to compare the impact of the milling process, powders were homogenized by mechanical stirring homogenization (MSH) too. For the two-homogenization process, three weight percent ratios were studied; 10%, 30%, and 50% w/w of BT in the HA matrix. The phase and crystallite size were analyzed by X-ray diffraction patterns (XRD); the BT-phase distribution in the coating was analyzed by backscattered electron image (BSE) with a scanning electron microscope (SEM); the energy-dispersive X-ray spectroscopy (EDS) analysis was used to determinate the Ca/P molar ratio of the coatings, the degree of adhesion (bonding strength) of coatings was determinate by pull-out test according to ASTM C633, and finally the nanomechanical properties was determinate by nanoindentation. In the results, the HEBM powder processing shows better efficiency in phase distribution, being the 30% (w/w) of BT in HA matrix that promotes the best bonding strength performance and failure type conduct (cohesive-type), on the other hand HEBM powder treatment promotes a slightly greater crystal phase stability and crystal shrank conduct against MSH; the HEBM promotes a better behavior in the nanomechanical properties of (i) adhesive strength, (ii) cohesive/adhesive failure-type, (iii) stiffness, (iv) elastic modulus, and (v) hardness properties.

Fabrication of Hydroxyapatite/Tantalum Composites by Pressureless Sintering in Different Atmosphere.

The effect of sintering atmosphere (air and Ar) and temperature (1100, 1200, 1300 °C) on the microstructure, mechanical properties, and bioactivity of hydroxyapatite/tantalum (HA/Ta) composites were systematically investigated by pressureless sintering of the mixture of HA and Ta powders. It shows that the sintering atmosphere greatly impacts the phase composition and microstructure of the HA/Ta composites. The higher diffusion of atoms promotes shrinkage and causes deeper reaction fusion between the HA matrix and Ta, which improved the interfacial binding of the HA/Ta composites. The refined grain structure and improved interfacial binding obtained within the Ar atmosphere compared to the air atmosphere benefit the mechanical properties. The maximum bending strength and shrinkage observed for the composites sintered at 1300 °C in the Ar atmosphere are 27.24 MPa and 6.65%, respectively. The cell counting kit-8 (CCK-8) method was used to investigate the in vitro cytocompatibility of HA/Ta composites. The results revealed that the HA/Ta composites sintered with different conditions have no cytotoxicity. The simulated body fluid (SBF) soaking results showed that all of the studied composites possess desirable bioactivity, as demonstrated by their ability to form calcium-deficient carbonate apatite layer on the surfaces. For composites sintered at 1300 °C, the surface apatite layer coverage of the composites obtained in the Ar atmosphere was increased by 139.7% than the ones obtained in air, which confirmed an enhanced bioactive mineralization ability. The results indicated that the HA/Ta composites sintered at 1300 °C in Ar possess desirable mechanical properties and bioactivity. This work opens up the new possibility for preparing HA-based composites and is of great value in biomedical applications.

Efficacy of Graphene Nanosheets on the Plasma Sprayed Hydroxyapatite Coating: Improved Strength, Toughness and In-Vitro Bioperformance With Osteoblast

Graphene nanosheet (GNS) reinforced HA coating on Ti6Al4V substrate, fabricated using plasma spray, was developed for biomedical applications. Microstructural observation corroborated that the adding GNSs homogeneously distributed in the GNS/HA coating with typical lamellar structure featured by GNSs acting as binder between the discrete HA splats. Meanwhile, GNSs were observed to get in direct contact with HA matrix and form a clean GNS-HA interface without interfacial product. Results of various indentation tests showed simultaneous improvement in both indentation yield strength (~379 MPa) and fracture toughness (0.78±0.17 MPam1/2 ), mainly attributing to synergetic toughening and strengthening mechanisms associated with the adding GNSs such as load transfer, GNS pull-out, inter-layer sliding of a GNS, crack branching, GNS bridging and crack deflection. In addition, the GNS/HA coating exhibited improved biocompatible with MG-63 cell in terms of its attachment, adhesion strength, proliferation and differentiation. Hence, the GNS/HA composite coating with improved strength, toughness and enhanced biocompatibility makes it a promising candidate for bone regeneration and implantation.

Efficacy of graphene nanosheets on the plasma sprayed hydroxyapatite coating: Improved strength, toughness and in-vitro bioperformance with osteoblast

Graphene nanosheet (GNS) reinforced HA coating on Ti6Al4V substrate, fabricated using plasma spray, was developed for biomedical applications. Microstructural observation corroborated that the adding GNSs homogeneously distributed in the GNS/HA coating with typical lamellar structure featured by GNSs acting as binder between the discrete HA splats. Meanwhile, GNSs were observed to get in direct contact with HA matrix and form a clean GNS-HA interface without interfacial product. Results of various indentation tests showed simultaneous improvement in both indentation yield strength (~379 MPa) and fracture toughness (0.78 ± 0.17 MPam1/2), mainly attributing to synergetic toughening and strengthening mechanisms associated with the adding GNSs such as load transfer, GNS pull-out, inter-layer sliding of a GNS, crack branching, GNS bridging and crack deflection. In addition, the GNS/HA coating exhibited improved biocompatible with MG-63 cell in terms of its attachment, adhesion strength, proliferation and differentiation. Hence, the GNS/HA composite coating with improved strength, toughness and enhanced biocompatibility makes it a promising candidate for bone regeneration and implantation.

A new Ag-nanostructured hydroxyapatite porous scaffold: Antibacterial effect and cytotoxicity study.

We report a new chemical method for the functionalization of Mg-hydroxyapatite (Mg-HA) scaffold with Ag nanoparticles (Ag NPs) integrating in one step both the synthesis of the Ag NPs and their nano-structuring into the HA matrix (Ag-Mg-HA scaffold). This method exploits a green photochemical synthesis and allows the direct growth of Ag NPs on the Mg-HA surface. The surface structure of Ag-Mg-HA scaffold, investigated by scanning electron microscopy, shows no significant changes in the morphology upon Ag NPs incorporation. The presence of Ag was confirmed by EDX analysis. TEM and spectroscopic investigations show Ag NPs spherical shaped with a mean diameter of about 20nm exhibiting the typical plasmon absorption band with maximum at 420nm. The antibacterial properties of Ag-Mg-HA scaffolds were tested against two bacterial strains, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results show excellent antibacterial properties achieving up to 99% and 100% reduction of colonies for both bacteria cultures after 24h of incubation and 100% of reduction after 48h of incubation. The cytotoxicity of Ag-Mg-HA was also in deep investigated assessing both cell proliferation and differentiation using hADSCs (human Adipose Derived Stem Cells) and testing data point at 0, 7, 14 and 24days. The results show cytotoxic effect with cell proliferation decreasing up to 90% at 24days and osteogenic differentiation inhibition. The observed cytotoxicity can be probable ascribed to the oxidative stress by ROS. Indeed, considering the effectiveness of the nanofunctionalization method and the excellent antibacterial properties showed by the Ag-Mg-HA scaffold, future works will be devoted to create nanofunctionalized scaffold satisfying both antimicrobial and osteo-regenerative properties.

A pericellular hyaluronan matrix is required for the morphological maturation of cortical neurons.

BackgroundHyaluronan (HA) is a major component of the extracellular matrix (ECM) and is involved in many cellular functions. In the adult brain, HA forms macromolecular aggregates around synapses and plays important roles in neural plasticity. In contrast to the well-characterized function of HA in the adult brain, its roles in the developing brain remain largely unknown. MethodsBiochemical and histochemical analyses were performed to analyze the amount, solubility, and localization of HA in the developing mouse brain. By combining in utero labeling, cell isolation, and in vitro cultures, we examined the expression of hyaluronan synthase (HAS) and morphological maturation of cortical neurons. ResultsThe amount of HA increased during perinatal development and decreased in the adult. HA existed as a soluble form in the early stages; however, its solubility markedly decreased during postnatal development. HA localized in cell-sparse regions in the embryonic stages, but was broadly distributed during the postnatal development of the cerebral cortex. Developing cortical neurons expressed both Has2 and Has3, but not Has1, suggesting the autonomous production of HA by neurons themselves. HA formed a pericellular matrix around the cell bodies and neurites of developing cortical neurons, and the inhibition of HA synthesis reduced neurite outgrowth. ConclusionThe formation of the pericellular HA matrix is essential for the proper morphological maturation of developing neurons. General significanceThis study provides new insights into the roles of hyaluronan in the brain.development.

Use of recombinant influenza vaccines expressing exogenous miRNAs for increased vaccine production

Abstract Vaccination remains the most effective means by which influenza virus infection can be controlled. Traditionally vaccine production has focused on egg-based technology. Increasingly cell culture-based vaccine production is being used to improve preparedness. Cell cultured based production methods offer significant advantages over traditional egg-based strategies by allowing (i) rapid scale-up (ii) elimination of allergic egg components and (iii) circumvention of issues relating to egg-adaption. Our aim was to improve influenza vaccines and preparedness through the establishment of mammalian cell (Vero)-based vaccines using plasmid-based recombinant flu constructs expressing exogenous miRNA19 (flu-miR19), a regulator of key host anti-viral pathways that has previously been shown to modulate influenza virus replication. We successfully rescued recombinant influenza viruses expressing miR19 using reverse genetics; validated expression of miR19 and showed increased virus replication in vitro that corresponded with increased HA titres and matrix gene expression. Knockdown of miR19 host target genes was confirmed through qRT-PCR to validate the mechanism of action. This new influenza vaccine platform is scalable and can be merged with existing production technology to offer rapid clinical translation and improve vaccine quality and production times. In summary, silencing of anti-viral host genes using a flu-miR resulted in an increase of influenza vaccine and HA antigen yield. We now plan to further augment antigen yield by propagating these viruses in enhanced Vero cell vaccine substrates.

Controlled adsorption and release of amoxicillin in GO/HA composite materials

Present work is aimed at preparing hybrid composites based on graphene oxide and hydroxyapatite as a matrix (GO/HA), which can be used as a template for drug delivery after chirurgical operation. Composite materials were synthesized through an in situ precipitation as simple and save-time method. The obtained materials were characterized using infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Hybrid materials were loaded with amoxicillin and the drug delivery during various periods of time was assessed with UV spectroscopy. During loading periods, it was noted that GO has a much larger cumulative drug concentration compared to hydroxyapatite and other composites. Similarly, and during the release process, amoxicillin is released much faster during the earlier stage of immersion before reaching a stationary state towards long periods of time. This variation was found to be dependent on the amount of GO in the HA matrix, as well as on the number of oxygen available on the GO sheets and the HA surfaces.

Drug Release Behavior of Doxorubicin Hydrochloride-Loaded Poly(L-Lactic Acid)/Hydroxyapatite/Gelatin by Surface Modification of Hydroxyapatite.

The doxorubicin hydrochloride (DOX)-loaded poly(L-lactic acid)/hydroxyapatite/gelatin (PLLA/a-HA/gelatin) particle was prepared by emulsion/solvent evaporation method using CH2Cl2 as a solvent. HA nanoparticles were prepared via a facile chemical precipitate method and HA nanoparticles were functionalized by adding aminopropyltriethoxysilane (APTS) under microwave radiation. The physical and chemical properties of HA and modified HA were characterized by XRD, TEM, FT-IR, and XPS. Furthermore, the release of DOX from PLLA/a-HA/gelatin was also estimated. Results indicated that HA was successfully functionalized via APTS and functionalized HA has primary amino groups on its surface which improved the surface chemical compatibility between HA and PLLA matrix. The prepared PLLA/a-HA/gelatin was considered as a drug release carrier to study sustained release behavior of doxorubicin hydrochloride (DOX). The PLLA/a-HA/gelatin can effectively prolong the release time of DOX and exhibits a stable and sustainable drug release which indicates that the PLLA/a-HA/gelatin nanocomposite material could serve as a potential carrier for novel drug release system.

In vivo monitoring of tumor distribution of hyaluronan polymeric micelles labeled or loaded with near-infrared fluorescence dye

Development of delivery systems which allow real-time visual inspection of tumors is critical for effective therapy. Near-infrared (NIR) fluorophores have a great potential for such an application. To overcome NIR dyes short blood circulation time and increase tumor accumulation, a NIR dye, cypate, was associated with oleyl hyaluronan, which can self-assemble into polymeric aggregates. The cypate association with oleyl hyaluronan was performed either by a covalent linkage, or physical entrapment. The two systems were compared for tumor targeting and contrast enhancement using BALB/c mice bearing 4T1 breast cancer tumors. Independently on the way of cypate association, it took more than 24 h from intravenous administration to detect NIR signal in tumors and the tumors were clearly visualized for 2 following weeks without substrate reinjection. Covalently linked cypate generated 2–3 fold stronger fluorescence signal than physically loaded cypate. This study demonstrates the potential of HA matrix to be used as carrier of contrast agents for non-invasive long-term tumor visualization.

Boron nitride nanoplatelets induced synergetic strengthening and toughening effects on splats and their boundaries of plasma sprayed hydroxyapatite coatings

Boron nitride nanoplatelets (BNNPs) with excellent mechanical properties were introduced into HA coatings fabricated through plasma spray in this research. SEM observation and Raman results revealed the added BNNPs retained their original structure even after harsh process and distributed homogeneously in the as-sprayed coatings. As compared with the monolithic HA coating, a 2.0 wt%BNNP/HA coating exhibited significant improvement (~ 40.3%) in fracture toughness and moderate enhancement (~ 20.0%) in indentation yield strength. Synergetic strengthening and toughening mechanisms which are operative through splat boundaries and individual splats were proposed. At splat boundaries, these embedded BNNPs induced stronger adhesion between the adjacent splats to resist splat sliding, which is evident from the fact that the calculated inter-splat friction force of an as-sprayed BNNP/HA coating was increased by ~7.3% at 2.0% BNNP weight fraction. Within splats, toughening mechanisms such as BNNP pullout, crack bridging by both anchored BNNPs and nanosized HA grains, crack deflection and crack propagation arrested by the embedded BNNPs were observed to improve toughness. Moreover, thermal mismatch between HA matrix and BNNPs during cooling process after plasma spray would induce the pre-existing dislocations formed around these BNNP nanofillers, which was assumed to hold out the effect of Orowan-type strengthening within splats.