Phase-Tunable Calcium Phosphate Biomaterials Synthesis and Application in Protein Delivery

Calcium phosphates (CaP) are important biomaterials used in tissue engineering and drug delivery, due to their biocompatibility, low toxicity, and osteoconductivity. However, controlling the phase of CaP, especially tricalcium phosphate (TCP), is very challenging under mild conditions, particularly when using one preparation protocol for all CaP phases. It is also crucial to produce these biomaterials economically and reproducibly. Herein, three of the most commonly employed CaP, including beta-tricalcium phosphate (β-TCP), dicalcium phosphate anhydrous (DCPA), and hydroxyapatite (HA) were, for the first time, successfully synthesized by altering the reaction solvent, using calcium acetate monohydrate as a precursor and a rapid microwave-assisted synthetic method. A variety of CaP particle morphologies were obtained, including elliptical and plate-shaped with different porosities. Compared with conventional heating, CaP biomaterials synthesized using microwave heating showed greater reproducibility, higher yields, and shorter reaction time. By varying the reaction solvents, morphologies and phases of CaP were controlled, leading to an enhanced protein bovine serum albumin (BSA) loading, with a higher BSA absorption observed according to the trend DCPA> β-TCP > HA. Furthermore, the phase, specific surface area, and pore size were shown to play decisive roles in protein desorption with a higher release amount observed according to the trend DCPA > β-TCP > HA. Finally, it is found that larger pores are also beneficial to BSA adsorption

The Answer is Blowing in the Wind

A 'News & Views' article -- no abstract

Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>B7 Costimulatory signal is essential to trigger T-cell activation upon the recognition of tumor antigens. This study examined the expression of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the presence of infiltrating lymphocytes and dendritic cells to assess their significance in patients with nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Expression of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes and follicular dendritic reticulum cells were immunohistochemically examined on the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50). The results were correlated with clinical outcome of patients.</p> <p>Results</p> <p>CD80 and CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases. Univariate analysis revealed that patients with CD80/CD86 expression had significantly better overall survival than those without it (P = 0.017), but after adjustment for stage, nodal status, and treatment, the expression of CD80/CD86 did not significantly correlate with overall survival. Expression of HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not appear to have impact on the survival of patients.</p> <p>Conclusion</p> <p>Expression of CD80 and CD86 costimulatory molecules appears to be a marker of better survival in patient with NPC.</p

Interface Engineering for Atomic Layer Deposited Alumina Gate Dielectric on SiGe Substrates.

Optimization of the interface between high-k dielectrics and SiGe substrates is a challenging topic due to the complexity arising from the coexistence of Si and Ge interfacial oxides. Defective high-k/SiGe interfaces limit future applications of SiGe as a channel material for electronic devices. In this paper, we identify the surface layer structure of as-received SiGe and Al2O3/SiGe structures based on soft and hard X-ray photoelectron spectroscopy. As-received SiGe substrates have native SiOx/GeOx surface layers, where the GeOx-rich layer is beneath a SiOx-rich surface. Silicon oxide regrows on the SiGe surface during Al2O3 atomic layer deposition, and both SiOx and GeOx regrow during forming gas anneal in the presence of a Pt gate metal. The resulting mixed SiOx-GeOx interface layer causes large interface trap densities (Dit) due to distorted Ge-O bonds across the interface. In contrast, we observe that oxygen-scavenging Al top gates decompose the underlying SiOx/GeOx, in a selective fashion, leaving an ultrathin SiOx interfacial layer that exhibits dramatically reduced Dit

Vertical current induced domain wall motion in MgO-based magnetic tunnel junction with low current densities

Shifting electrically a magnetic domain wall (DW) by the spin transfer mechanism is one of the future ways foreseen for the switching of spintronic memories or registers. The classical geometries where the current is injected in the plane of the magnetic layers suffer from a poor efficiency of the intrinsic torques acting on the DWs. A way to circumvent this problem is to use vertical current injection. In that case, theoretical calculations attribute the microscopic origin of DW displacements to the out-of-plane (field-like) spin transfer torque. Here we report experiments in which we controllably displace a DW in the planar electrode of a magnetic tunnel junction by vertical current injection. Our measurements confirm the major role of the out-of-plane spin torque for DW motion, and allow to quantify this term precisely. The involved current densities are about 100 times smaller than the one commonly observed with in-plane currents. Step by step resistance switching of the magnetic tunnel junction opens a new way for the realization of spintronic memristive devices

Interface Engineering for Atomic Layer Deposited Alumina Gate Dielectric on SiGe Substrates.

Optimization of the interface between high-k dielectrics and SiGe substrates is a challenging topic due to the complexity arising from the coexistence of Si and Ge interfacial oxides. Defective high-k/SiGe interfaces limit future applications of SiGe as a channel material for electronic devices. In this paper, we identify the surface layer structure of as-received SiGe and Al2O3/SiGe structures based on soft and hard X-ray photoelectron spectroscopy. As-received SiGe substrates have native SiOx/GeOx surface layers, where the GeOx-rich layer is beneath a SiOx-rich surface. Silicon oxide regrows on the SiGe surface during Al2O3 atomic layer deposition, and both SiOx and GeOx regrow during forming gas anneal in the presence of a Pt gate metal. The resulting mixed SiOx-GeOx interface layer causes large interface trap densities (Dit) due to distorted Ge-O bonds across the interface. In contrast, we observe that oxygen-scavenging Al top gates decompose the underlying SiOx/GeOx, in a selective fashion, leaving an ultrathin SiOx interfacial layer that exhibits dramatically reduced Dit

Health care seeking among detained undocumented migrants: a cross-sectional study

BACKGROUND: As in many European countries, access to care is decreased for undocumented migrants in the Netherlands due to legislation. Studies on the health of undocumented migrants in Europe are scarce and focus on care-seeking migrants. Not much is known on those who do not seek care. METHODS: This cross-sectional study includes both respondents who did and did not seek care, namely undocumented migrants who have been incarcerated in a detention centre while awaiting expulsion to their country of origin. A consecutive sample of all new arrivals was studied. Data were collected through structured interviews and reviews of medical records. RESULTS: Among the 224 male migrants who arrived at the detention centre between May and July 2008, 173 persons were interviewed. 122 respondents met inclusion criteria. Only half of the undocumented migrants in this study knew how to get access to medical care in the Netherlands if in need. Forty-six percent of respondents reported to have sought medical help during their stay in the Netherlands while having no health insurance (n = 57). Care was sought most frequently for injuries and dental problems. About 25% of these care seekers reported to have been denied care by a health care provider. Asian migrants were significantly less likely to seek care when compared to other ethnic groups, independent from age, chronic health problems and length of stay in the Netherlands. CONCLUSION: The study underlines the need for a better education of undocumented patients and providers concerning the opportunities for health care in the Netherlands. Moreover, there is a need to further clarify the reasons for the denial of care to undocumented patients, as well as the barriers to health care as perceived by undocumented migrants

Tailoring degree of esterification and branching of poly(glycerol sebacate) by energy efficient microwave irradiation

Poly(glycerol sebacate) (PGS) is known as an exciting biomaterial owing to its tunable mechanical properties and controllable degradation rate. However, it is always challenging to control these properties. In this study, we have proposed a solvent-based system to provide a better control of reaction temperature in a microwave cavity, which can minimize evaporation of monomers, and water was collected to analyse the degree of esterification. Pre-PGSs with varied degrees of esterification were prepared using both single mode and multimode microwave cavity irradiation (MI) in this solvent-based reaction system. For a similar degree of esterification of pre-PGSs, the reaction time was almost halved with a better control on mechanical properties by single mode MI compared to multimode MI. Furthermore, the single mode MI approach was compared with the conventional heating (CH) approach. The mechanical properties and degradation rate of PGSs can be controlled readily by using the single mode MI approach compared to CH, which are crucial for their application as a biomaterial. It has been found that the single mode MI not only accelerates the pre-polymerisation process rate by six times, but also speeds up the curing time to the same extent. The Young's modulus of PGSs prepared by single mode MI is increased from 0.77 to 3.14 MPa when the degree of esterification is 66.82%, which is 50% higher than that reported in the literature. Furthermore, PGS using a highly branched pre-PGS prepared by the single mode MI method has a large degree of flexibility. It can achieve a much higher Young's modulus than that obtained by CH with a short curing time (<10 hours). In addition, the residual mass of PGSs prepared by single mode MI is varied from 78.54% to 92.96% compared to the CH method that ranges from 84.24% to 93.31%. Thus, these highly branched PGSs produced by single mode MI also show a wider degradation window (approximately 59% higher degree of flexibility than the CH method), which is found to be highly dependent on the degree of esterification and curing time of the pre-polymer, and controlled by branching

BMP2 Is superior to BMP4 for promoting human muscle-derived stem cell-mediated bone regeneration in a critical-sized calvarial defect model

Muscle-derived cells have been successfully isolated using a variety of different methods and have been shown to possess multilineage differentiation capacities, including an ability to differentiate into articular cartilage and bone in vivo; however, the characterization of human muscle-derived stem cells (hMDSCs) and their bone regenerative capacities have not been fully investigated. Genetic modification of these cells may enhance their osteogenic capacity, which could potentially be applied to bone regenerative therapies. We found that hMDSCs, isolated by the preplate technique, consistently expressed the myogenic marker CD56, the pericyte/endothelial cell marker CD146, and the mesenchymal stem cell markers CD73, CD90, CD105, and CD44 but did not express the hematopoietic stem cell marker CD45, and they could undergo osteogenic, chondrogenic, adipogenic, and myogenic differentiation in vitro. In order to investigate the osteoinductive potential of hMDSCs, we constructed a retroviral vector expressing BMP4 and GFP and a lentiviral vector expressing BMP2. The BMP4-expressing hMDSCs were able to undergo osteogenic differentiation in vitro and exhibited enhanced mineralization compared to nontransduced cells; however, when transplanted into a calvarial defect, they failed to regenerate bone. Local administration of BMP4 protein and cell pretreatment with N-acetylcysteine (NAC), which improves cell survival, did not enhance the osteogenic capacity of the retro-BMP4-transduced cells. In contrast, lenti-BMP2-transduced hMDSCs not only exhibited enhanced in vitro osteogenic differentiation but also induced robust bone formation and nearly completely healed a critical-sized calvarial defect in CD-1 nude mice 6 weeks following transplantation. Herovici's staining of the regenerated bone demonstrated that the bone matrix contained a large amount of type I collagen. Our findings indicated that the hMDSCs are likely mesenchymal stem cells of muscle origin and that BMP2 is more efficient than BMP4 in promoting the bone regenerative capacity of the hMDSCs in vivo. © 2013 Cognizant Comm. Corp

Clinical correlation of nuclear survivin in esophageal squamous cell carcinoma

To examine the correlation of survivin (both total and nuclear survivin) with clinicopathological parameters of esophageal squamous cell carcinoma (ESCC) patients. Tumors and non-tumor tissues near the proximal resection margins were resected from ESCC patients undergone esophagectomy. Quantitative polymerase chain reaction (qPCR) was performed to detect survivin mRNA expression level in the 10 paired tumor and adjacent non-tumor tissues. To confirm with the clinical situation, survivin mRNA and protein expression were measured by qPCR and immunoblot, respectively, in 5 ESCC cell lines and a non-neoplastic esophageal epithelial cell line. Immunohistochemistry was employed to reveal the cellular localization of survivin in tumor tissues isolated from the 64 ESCC patients undergone surgery alone. Up-regulation of survivin mRNA and protein was found in 5 ESCC lines (HKESC-1, HKESC-2, HKESC-3, HKESC-4, and SLMT-1) when compared to a non-neoplastic esophageal epithelial cell line NE-1. In particular, HKESC-3, HKESC-4, and SLMT-1 cells demonstrated ~50-fold increase in survivin mRNA. High level of survivin mRNA in tumor tissues when compared to non-tumor tissues was found in 70 % (7 of 10) of clinical cases. The increase in expression ranged from ~twofold to ~16-fold. Immunohistochemistry results showed that survivin was found at the cell nuclei in all specimens examined. Nuclear expression of survivin was inversely associated with the likelihood of developing nodal metastasis (p = 0.021) and significantly associated with early-stage ESCC (p = 0.039). Nuclear survivin could serve as a marker for indicating disease status in ESCC patients. © 2012 The Author(s).published_or_final_versio