3D porous Ti6Al4V-beta-tricalcium phosphate scaffolds directly fabricated by additive manufacturing.

3D Ti6Al4V-beta-tricalcium phosphate (TCP) hybrid scaffolds with interconnected porous network and controllable porosity and pore size were successfully produced by three-dimensional fiber deposition (3DF). The macrostructure of scaffolds was determined by the 3D design, whereas the micro- and submicron structure were derived from the Ti6Al4V powder sintering and the crystalline TCP powder, respectively. Ti6Al4V-TCP slurry was developed for 3DF by optimizing the TCP powder size, Ti6Al4V-to-TCP powder ratio and Ti6Al4V-TCP powder content. Moreover, the air pressure and fiber deposition rate were optimized. A maximum achievable ceramic content in the Ti6Al4V-TCP slurry that enables 3DF manufacturing was 10 wt%. The chemical analysis showed that limited contamination occurred during sintering. The compressive strength and Young's modulus of the scaffolds exhibited values between those of cancellous and cortical bone. The 3D Ti6Al4V-TCP scaffolds with 10 wt% TCP allowed deposition of a calcium phosphate layer on the surface in a simulated body fluid. Cumulative release of calcium and phosphate ions from the scaffolds was observed in a simulated physiological solution, in contrast to a cell culture medium. A pilot in vivo study, in which the scaffolds were implanted intramuscularly in dogs showed ectopic bone formation in the Ti6Al4V-TCP scaffolds with 10 wt% TCP, showing their osteoinductive potential. The porous 3D Ti6Al4V-TCP scaffolds developed here combine the mechanical properties of the metal with the bioactivity of the ceramic and are therefore likely to yield more effective strategies to control the implant-bone interface and thereby improve long-term clinical results in orthopaedics and craniomaxillofacial surgery. STATEMENT OF SIGNIFICANCE: In this work, 3D porous hybrid scaffolds made of a titanium alloy and a beta-tricalcium phosphate ceramic (Ti6Al4V-TCP) were developed using the direct additive manufacturing technique 3D fiber deposition. Upon optimization of the powders and slurry, scaffolds with up to 10 wt.% TCP with good mechanical properties and controllable porous structure at different length scales were successfully manufactured. A preliminary in vivo study in an intramuscular model demonstrated that the addition of TCP to the metal alloy improved its bioactivity. The combination of the two materials and the use of a direct additive manufacturing technique resulted in scaffolds that may lead to more effective strategies to control the implant-bone interface and thereby improve long-term clinical results in orthopaedics and craniomaxillofacial surgery.

Hyperlipidemia Alters Regulatory T Cell Function and Promotes Resistance to Tolerance Induction Through Costimulatory Molecule Blockade.

Recent work from our laboratory has shown that hyperlipidemia promotes accelerated rejection of vascularized cardiac allografts in mice by inducing anti-donor Th17 reactivity and production of IL-17. Here, we show that hyperlipidemia also affects FoxP3(+) regulatory T cells (Tregs). Hyperlipidemia promotes the development of Tregs that express low levels of CD25. Hyperlipidemia also promotes a decrease in central Tregs and an increase in effector Tregs that appears to account for the increase in the frequency of CD25(low) Tregs. Alterations in Treg subsets also appear to lead to alterations in Treg function. The ability of FoxP3(+) , CD25(high) , CD4(+) Tregs from hyperlipidemic mice to inhibit proliferation of effector T cells stimulated with anti-CD3 and CD28 was reduced when compared with Tregs from control mice. Regulatory T cells isolated from hyperlipidemic recipients exhibit increased activation of Akt, and a reduction in Bim levels that permits the expansion of FoxP3(+) CD25(low) CD4(+) T cells. Hyperlipidemic mice were also resistant to tolerance induction using costimulatory molecule blockade consisting of anti-CD154 and CTLA4Ig, a strategy that requires Tregs. Together, our data suggest that hyperlipidemia profoundly affects Treg subsets and function as well as the ability to induce tolerance.

Human immunodeficiency virus infection in a child presenting as herpes zoster ophthalmicus.

Herpes zoster is mainly a disease of the elderly. Its occurrence in younger age should be viewed with suspicion. A 9-year-old boy presented with herpes zoster ophthalmicus. He had a history of abdominal surgery one and half years back during which he had received blood transfusion. A year following the surgery he developed general malaise and fever with progressive weight loss. He was treated by local doctors. Subsequently he developed eruptions of blisters around right eye for a duration of 8 days, with which he presented to the department of ophthalmology, Pt JNM Medical College, Raipur. On investigations he was found to have infected with human immunodeficiency virus. Systemic acyclovir along with antiretroviral treatment was started, to which he showed favourable response.