Toward microfluidic integration of respiratory and renal organ support in a single cartridge.

BACKGROUND: Extracorporeal organ assist devices provide lifesaving functions for acutely and chronically ill patients suffering from respiratory and renal failure, but their availability and use is severely limited by an extremely high level of operational complexity. While current hollow fiber-based devices provide high-efficiency blood gas transfer and waste removal in extracorporeal membrane oxygenation (ECMO) and hemodialysis, respectively, their impact on blood health is often highly deleterious and difficult to control. Further challenges are encountered when integrating multiple organ support functions, as is often required when ECMO and ultrafiltration (UF) are combined to deal with fluid overload in critically ill patients, necessitating an unwieldy circuit containing two separate cartridges. METHODS: We report the first laboratory demonstration of simultaneous blood gas oxygenation and fluid removal in single microfluidic circuit, an achievement enabled by the microchannel-based blood flow configuration of the device. Porcine blood is flowed through a stack of two microfluidic layers, one with a non-porous, gas-permeable silicone membrane separating blood and oxygen chambers, and the other containing a porous dialysis membrane separating blood and filtrate compartments. RESULTS: High levels of oxygen transfer are measured across the oxygenator, while tunable rates of fluid removal, governed by the transmembrane pressure (TMP), are achieved across the UF layer. Key parameters including the blood flow rate, TMP and hematocrit are monitored and compared with computationally predicted performance metrics. CONCLUSIONS: These results represent a model demonstration of a potential future clinical therapy where respiratory support and fluid removal are both realized through a single monolithic cartridge.

Asymptomatic Intracardiac Cement Embolism Following Kyphoplasty.

Cement extravasation can occur during vertebral body augmentation such as kyphoplasty and vertebroplasty with diverse presentation and resultant treatment. The cement can embolize through venous vasculature to the thorax where it poses a potential threat to the cardiovascular and pulmonary systems. A thorough risk-benefit analysis should be conducted to select the appropriate treatment course. We present an asymptomatic case of cement extravasation to the heart and lungs during kyphoplasty.

Employing PEG crosslinkers to optimize cell viability in gel phase bioinks and tailor post printing mechanical properties.

The field of 3D bioprinting has rapidly grown, yet the fundamental ability to manipulate material properties has been challenging with current bioink methods. Here, we change bioink properties using our PEG cross-linking (PEGX) bioink method with the objective of optimizing cell viability while retaining control of mechanical properties of the final bioprinted construct. First, we investigate cytocompatible, covalent cross-linking chemistries for bioink synthesis (e.g. Thiol Michael type addition and bioorthogonal inverse electron demand Diels-Alder reaction). We demonstrate these reactions are compatible with the bioink method, which results in high cell viability. The PEGX method is then exploited to optimize extruded cell viability by manipulating bioink gel robustness, characterized by mass flow rate. Below a critical point, cell viability linearly decreases with decreasing flow rates, but above this point, high viability is achieved. This work underscores the importance of building a foundational understanding of the relationships between extrudable bioink properties and cell health post-printing to more efficiently tune material properties for a variety of tissue and organ engineering applications. Finally, we also develop a post-printing, cell-friendly cross-linking strategy utilizing the same reactions used for synthesis. This secondary cross-linking leads to a range of mechanical properties relevant to soft tissue engineering as well as highly viable cell-laden gels stable for over one month in culture. STATEMENT OF SIGNIFICANCE: We demonstrate that a PEG crosslinking bioink method can be used with various cytocompatible, covalent cross-linking reactions: Thiol Michael type addition and tetrazine-norbornene click. The ability to vary bioink chemistry expands candidate polymers, and therefore can expedite development of new bioinks from unique polymers. We confirm post-printed cell viability and are the first to probe, in covalently cross-linked inks, how cell viability is impacted by different flow properties (mass flow rate). Finally, we also present PEG cross-linking as a new method of post-printing cross-linking that improves mechanical properties and stability while maintaining cell viability. By varying the cross-linking reaction, this method can be applicable to many types of polymers/inks for easy adoption by others investigating bioinks and hydrogels.