Carbonated Nano Hydroxyapatite Crystal Growth Modulated by Poly(ethylene glycol) with Different Molecular Weights

The effects of poly­(ethylene glycol) (PEG) molecular weights on nano hydroxyapatite (n-HA) crystal growth were studied, and a possible mechanism was proposed. n-HA crystals were synthesized in the presence of PEG with different molecular weights via hydrothermal method. Transmission electron microscopy (TEM) analysis showed that the presence of PEG increased the size of n-HA crystals; PEG with larger molecular weights produced larger n-HA crystals. High-resolution TEM observation indicated that all of the n-HA crystals tended to grow along the ⟨002⟩ axis. X-ray diffraction patterns showed that all of the samples consisted of only the HA phase. Besides, PEG increased the crystallinity of n-HA crystals, and this effect was more significant for PEGs with larger molecular weights. Fourier transform infrared results further revealed that all of the crystals were carbonated HA. Thermogravimetry/differential scanning calorimetry analysis detected PEG residues on n-HA particles. To thoroughly study the modulating mechanism of PEGs on n-HA crystal growth, n-HA samples heat-treated for various times were prepared in the presence of PEG20000, and a possible mechanism in which PEG modulated the growth of n-HA crystals was discussed

Surface Structure of Hydroxyapatite from Simulated Annealing Molecular Dynamics Simulations

The surface structure of hydroxyapatite (HAP) is crucial for its bioactivity. Using a molecular dynamics simulated annealing method, we studied the structure and its variation with annealing temperature of the HAP (100) surface. In contrast to the commonly used HAP surface model, which is sliced from HAP crystal and then relaxed at 0 K with first-principles or force-field calculations, a new surface structure with gradual changes from ordered inside to disordered on the surface was revealed. The disordering is dependent on the annealing temperature, <i>T</i>_max. When <i>T</i>_max increases up to the melting point, which was usually adopted in experiments, the disordering increases, as reflected by its radial distribution functions, structural factors, and atomic coordination numbers. The disordering of annealed structures does not show significant changes when <i>T</i>_max is above the melting point. The thickness of disordered layers is about 10 Å. The surface energy of the annealed structures at high temperature is significantly less than that of the crystal structure relaxed at room temperature. A three-layer model of interior, middle, and surface was then proposed to describe the surface structure of HAP. The interior layer retains the atomic configurations in crystal. The middle layer has its atoms moved and its groups rotated about their original locations. In the surface layer, the atomic arrangements are totally different from those in crystal. In particular for the hydroxyl groups, they move outward and cover the Ca²⁺ ions, leaving holes occupied by the phosphate groups. Our study suggested a new model with disordered surface structures for studying the interaction of HAP-based biomaterials with other molecules

A summary of tissue response to the three types of ceramics in different animals.

<p>A summary of tissue response to the three types of ceramics in different animals.</p

SEM micrographs showing macrostructure (A–C) and surface microstructure (D–F) of BCP1100 (A,D), BCP1200 (B,E) and HA1200 (C,F).

<p>All ceramics were porous with similar macroporous structure (A–C). The surface of the BCP1100 (D) ceramic exhibited smaller grains and a larger number of micropores than the chemically identical BCP1200, that was sintered at 1200°C (E). Grain size and number of micropores in HA1200 were between those of BCP110 and BCP1200 (F), which is in accordance with specific weight measurements in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107044#pone-0107044-t001" target="_blank">Table 1</a>. Scale bar = 1 mm for A–C and 10 µm for D–F.</p

XRD patterns of the three ceramics.

<p>The patterns of BCP1100 and BCP1200 demonstrated biphasic nature of the ceramics consisting of HA and β-TCP. No apparent differences were found as a result of difference in sintering temperature. The pattern of HA1200 was typical of phase-pure hydroxyapatite.</p

Histological evaluation of bone formation upon implantation of the three ceramics in dorsal muscles of dogs for 12 weeks.

<p>The highest amount of osteoid and ectopic bone were observed in BCP1100 (A), followed by BCP1200 (B) an HA1200 (C). In all cases, bone was trabecular in appearance, with laminar bone and osteocytes contained in the lacunae, and infiltrated by blood vessels. Decalcified sections, Masson’s trichrome staining, magnification = ×100, scale bar = 200 µm; V→Blood vessel, CT→Connective tissue, M→Material, O→Osteoid tissue, B→Bone.</p

Histological evaluation of tissue formation in the three ceramics upon intramuscular implantation in rats, rabbits and dogs.

<p>Representative images showing tissue response to BCP1100 (A, D, G), BCP1200 (B, E, H) and HA1200 (C, F, I) upon implantation in the femoral muscle of rat, dorsal muscle of rabbit and dog for 6 weeks. Decalcified sections, HE Staining, magnification = ×100, scale bar = 200 µm; V→ Blood vessel, CT→Connective tissue, M→Material, O→Osteoid tissue, B→Bone.</p

Physico-chemical characterization of biphasic calcium phosphate sintered at 1100°C (BCP1100), of biphasic calcium phosphate sintered at 1200°C (BCP1200) and of phase-pure hydroxyapatite sintered at 1200°C (HA1200).

<p>Physico-chemical characterization of biphasic calcium phosphate sintered at 1100°C (BCP1100), of biphasic calcium phosphate sintered at 1200°C (BCP1200) and of phase-pure hydroxyapatite sintered at 1200°C (HA1200).</p

Reduction-Degradable Polymeric Micelles Decorated with PArg for Improving Anticancer Drug Delivery Efficacy

In this study, five kinds of reduction-degradable polyamide amine-<i>g</i>-polyethylene glycol/polyarginine (PAA-<i>g</i>-PEG/PArg) micelles with different proportions of hydrophilic and hydrophobic segments were synthesized as novel drug delivery vehicles. Polyarginine not only acted as a hydrophilic segment but also possessed a cell-penetrating function to carry out a rapid transduction into target cells. Polyamide amine-<i>g</i>-polyethylene glycol (PAA-<i>g</i>-PEG) was prepared for comparison. The characterization and antitumor effect of the DOX-incorporated PAA-<i>g</i>-PEG/PArg cationic polymeric micelles were investigated <i>in vitro</i> and <i>in vivo</i>. The cytotoxicity experiments demonstrated that the PAA-<i>g</i>-PEG/PArg micelles have good biocompatibility. Compared with DOX-incorporated PAA-<i>g</i>-PEG micelles, the DOX-incorporated PAA-<i>g</i>-PEG/PArg micelles were more efficiently internalized into human hepatocellular carcinoma (HepG2) cells and more rapidly released DOX into the cytoplasm to inhibit cell proliferation. In the 4T1-bearing nude mouse tumor models, the DOX-incorporated PAA-<i>g</i>-PEG/PArg micelles could efficiently accumulate in the tumor site and had a longer accumulation time and more significant aggregation concentration than those of PAA-<i>g</i>-PEG micelles. Meanwhile, it excellently inhibited the solid tumor growth and extended the survival period of the tumor-bearing Balb/c mice. These results could be attributed to their appropriate nanosize and the cell-penetrating peculiarity of polyarginine as a surface layer. The PAA-<i>g</i>-PEG/PArg polymeric micelles as a safe and high efficiency drug delivery system were expected to be a promising delivery carrier that targeted hydrophobic chemotherapy drugs to tumors and significantly enhanced antitumor effects

NIR-to-Red Upconversion Nanoparticles with Minimized Heating Effect for Synchronous Multidrug Resistance Tumor Imaging and Therapy

Lanthanide-doped upconversion nanoparticles (UCNPs), especially the 808 nm activated UCNPs, are promising imaging agents for biological applications because of their minimal tissue overheating effects and low autofluorescence background. Optimizing the emission peaks located in the “biological window (600–1100 nm)” is of vital importance to obtain the maximum penetration depth and intense deep tissue imaging. On the other hand, because of the widely existing multidrug resistance (MDR) of tumor cells, traditional tumor chemotherapy often fails to achieve the desired effect. Herein, a new type of 808 nm excited pure red luminescence core–shell Nd³⁺-sensitized NaY­(Mn)­F₄:Yb/Er@NaYbF₄:Nd UCNPs (CSUCNPs) was designed and synthesized for deep tissue imaging and MDR tumor diagnosis with a minimized heating effect. In the meanwhile, d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) coating was introduced to endow CSUCNPs with capabilities of drug loading and overcoming MDR. The in vitro cytotoxicity test revealed that CSUCNPs-TPGS-doxorubicin (D-CSUCT) had excellent MDR cancer cell killing efficacy. The in vivo test showed that D-CSUCT can target the tumor site by enhanced retention effect, and the intense luminescent signals from the tumor site in the deep tissue were detected. Generally, this work shows D-CSUCT can overcome the MDR effect, diagnose the tumor, inhibit tumor growth, and induce tumor cells necrosis and apoptosis, without causing damage to major organs and other side effects. Overall, the study demonstrates the conjugation of red-emitted UCNPs with a minimized heating effect and that the anti-MDR carrier is highly promising for developing multifunctional theranostic system with effective simultaneous diagnosis and for multidrug-resistant tumor treatment