Recent advances in 3D printing of biomaterials.

3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described. Examples are highlighted to illustrate progress of each technology in tissue engineering, and key limitations are identified to motivate future research and advance this fascinating field of advanced manufacturing

Translational aspects of cardiac cell therapy.

Cell therapy has been intensely studied for over a decade as a potential treatment for ischaemic heart disease. While initial trials using skeletal myoblasts, bone marrow cells and peripheral blood stem cells showed promise in improving cardiac function, benefits were found to be short-lived likely related to limited survival and engraftment of the delivered cells. The discovery of putative cardiac 'progenitor' cells as well as the creation of induced pluripotent stem cells has led to the delivery of cells potentially capable of electromechanical integration into existing tissue. An alternative strategy involving either direct reprogramming of endogenous cardiac fibroblasts or stimulation of resident cardiomyocytes to regenerate new myocytes can potentially overcome the limitations of exogenous cell delivery. Complimentary approaches utilizing combination cell therapy and bioengineering techniques may be necessary to provide the proper milieu for clinically significant regeneration. Clinical trials employing bone marrow cells, mesenchymal stem cells and cardiac progenitor cells have demonstrated safety of catheter based cell delivery, with suggestion of limited improvement in ventricular function and reduction in infarct size. Ongoing trials are investigating potential benefits to outcome such as morbidity and mortality. These and future trials will clarify the optimal cell types and delivery conditions for therapeutic effect

Osteoblast interactions within a biomimetic apatite microenvironment.

Numerous reports have shown that accelerated apatites can mediate osteoblastic differentiation in vitro and bone formation in vivo. However, how cells interact within the apatite microenvironment remains largely unclear, despite the vast literature available today. In response, this study evaluates the in vitro interactions of a well-characterized osteoblast cell line (MC3T3-E1) with the apatite microenvironment. Specifically, cell attachment, spreading, and viability were evaluated in the presence and absence of serum proteins. Proteins were found to be critical in the mediation of cell-apatite interactions, as adherence of MC3T3-E1 cells to apatite surfaces without protein coatings resulted in significant levels of cell death within 24 h in serum-free media. In the absence of protein-apatite interaction, cell viability could be "rescued" upon treatment of MC3T3-E1 cells with inhibitors to phosphate (PO(4) (3-)) transport, suggesting that PO(4) (3-) uptake may play a role in viability. In contrast, rescue was not observed upon treatment with calcium (Ca(2+)) channel inhibitors. Interestingly, a rapid "pull-down" of extracellular Ca(2+) and PO(4) (3-) ions onto the apatite surface could be measured upon the incubation of apatites with α-MEM, suggesting that cells may be subject to changing levels of Ca(2+) and PO(4) (3-) within their microenvironment. Therefore, the biomimetic apatite surface may significantly alter the microenvironment of adherent osteoblasts and, as such, be capable of affecting both cell survival and differentiation

Photocurable Bioink for the Inkjet 3D Pharming of Hydrophilic Drugs.

Novel strategies are required to manufacture customized oral solid dosage forms for personalized medicine applications. 3D Pharming, the direct printing of pharmaceutical tablets, is an attractive strategy, since it allows for the rapid production of solid dosage forms containing custom drug dosages. This study reports on the design and characterization of a biocompatible photocurable pharmaceutical polymer for inkjet 3D printing that is suitable for hydrophilic active pharmaceutical ingredients (API). Specifically, hyaluronic acid was functionalized with norbornene moieties that, in the presence of poly(ethylene) glycol dithiol, Eosin Y as a photoinitiator, and a visible light source, undergoes a rapid step-growth polymerization reaction through thiol-ene chemistry. The engineered bioink was loaded with Ropinirole HCL, dispensed through a piezoelectric nozzle onto a blank preform tablet, and polymerized. Drug release analysis of the tablet resulted in 60% release within 15 min of tablet dissolution. The study confirms the potential of inkjet printing for the rapid production of tablets through the deposition of a photocurable bioink designed for hydrophilic APIs

The Cure: Making a game of gene selection for breast cancer survival prediction

Motivation: Molecular signatures for predicting breast cancer prognosis could greatly improve care through personalization of treatment. Computational analyses of genome-wide expression datasets have identified such signatures, but these signatures leave much to be desired in terms of accuracy, reproducibility and biological interpretability. Methods that take advantage of structured prior knowledge (e.g. protein interaction networks) show promise in helping to define better signatures but most knowledge remains unstructured. Crowdsourcing via scientific discovery games is an emerging methodology that has the potential to tap into human intelligence at scales and in modes previously unheard of. Here, we developed and evaluated a game called The Cure on the task of gene selection for breast cancer survival prediction. Our central hypothesis was that knowledge linking expression patterns of specific genes to breast cancer outcomes could be captured from game players. We envisioned capturing knowledge both from the players prior experience and from their ability to interpret text related to candidate genes presented to them in the context of the game. Results: Between its launch in Sept. 2012 and Sept. 2013, The Cure attracted more than 1,000 registered players who collectively played nearly 10,000 games. Gene sets assembled through aggregation of the collected data clearly demonstrated the accumulation of relevant expert knowledge. In terms of predictive accuracy, these gene sets provided comparable performance to gene sets generated using other methods including those used in commercial tests. The Cure is available at http://genegames.org/cure

Faraday Instability in a Surface-Frozen Liquid

Faraday surface instability measurements of the critical acceleration, a_c, and wavenumber, k_c, for standing surface waves on a tetracosanol (C_24H_50) melt exhibit abrupt changes at T_s=54degC above the bulk freezing temperature. The measured variations of a_c and k_c vs. temperature and driving frequency are accounted for quantitatively by a hydrodynamic model, revealing a change from a free-slip surface flow, generic for a free liquid surface (T>T_s), to a surface-pinned, no-slip flow, characteristic of a flow near a wetted solid wall (T < T_s). The change at T_s is traced to the onset of surface freezing, where the steep velocity gradient in the surface-pinned flow significantly increases the viscous dissipation near the surface.Comment: 4 pages, 3 figures. Physical Review Letters (in press

Reducing Constraints on Quantum Computer Design by Encoded Selective Recoupling

The requirement of performing both single-qubit and two-qubit operations in the implementation of universal quantum logic often leads to very demanding constraints on quantum computer design. We show here how to eliminate the need for single-qubit operations in a large subset of quantum computer proposals: those governed by isotropic and XXZ,XY-type anisotropic exchange interactions. Our method employs an encoding of one logical qubit into two physical qubits, while logic operations are performed using an analogue of the NMR selective recoupling method.Comment: 5 pages, 1 table, no figures. Published versio