Inorganic-Organic Interpenetrating Network Hydrogels as Tissue-Integrating Luminescent Implants: Physicochemical Characterization and Preclinical Evaluation.

Sensors capable of accurate, continuous monitoring of biochemistry are crucial to the realization of personalized medicine on a large scale. Great strides have been made to enhance tissue compatibility of long-term in vivo biosensors using biomaterials strategies such as tissue-integrating hydrogels. However, the low level of oxygen in tissue presents a challenge for implanted devices, especially when the biosensing function relies on oxygen as a measure-either as a primary analyte or as an indirect marker to transduce levels of other biomolecules. This work presents a method of fabricating inorganic-organic interpenetrating network (IPN) hydrogels to optimize the oxygen transport through injectable biosensors. Capitalizing on the synergy between the two networks, various physicochemical properties (e.g., swelling, glass transition temperature, and mechanical properties) are shown to be independently adjustable while maintaining a 250% increase in oxygen permeability relative to poly(2-hydroxyethyl methacrylate) controls. Finally, these gels, when functionalized with a Pd(II) benzoporphyrin phosphor, track tissue oxygen in real time for 76 days as subcutaneous implants in a porcine model while promoting tissue ingrowth and minimizing fibrosis around the implant. These findings support IPN networks for fine-tuned design of implantable biomaterials in personalized medicine and other biomedical applications.

Composite Hydrogels with Engineered Microdomains for Optical Glucose Sensing at Low Oxygen Conditions.

There is a growing need for advanced tools that enable frequent monitoring of biomarkers for precision medicine. In this work, we present a composite hydrogel-based system providing real-time optical bioanalyte monitoring. The responsive material, alginate-in-alginate (AnA), is comprised of an alginate hydrogel with embedded bioactive, nanofilm-coated phosphorescent microdomains; palladium tetracarboxyphenylporphyrin serves as an optical indicator, glucose oxidase as a model enzyme, and layer-by-layer deposited polyelectrolyte multilayers (PEMs) as the diffusion barrier. Glutaraldehyde crosslinking of the nanofilms resulted in a dramatic reduction in glucose diffusion (179%) while oxygen transport was not significantly affected. The responses of the AnA hydrogels to step changes of glucose at both ambient and physiological oxygen levels were evaluated, revealing controlled tuning of sensitivity and dynamic range. Stability, assessed by alternately exposing the responsive AnA hydrogels to extremely high and zero glucose concentrations, resulted in no significant difference in the response over 20 cycles. These AnA hydrogels represent an attractive approach to biosensing based on biocompatible materials that may be used as minimally-invasive, implantable devices capable of optical interrogation. The model glucose-responsive composite material studied in this work will serve as a template that can be translated for sensing additional analytes (e.g., lactate, urea, pyruvate, cholesterol) and can be used for monitoring other chronic conditions.

Composite Hydrogels Containing Bioactive Microreactors for Optical Enzymatic Lactate Sensing.

Continuously monitoring specific biomarkers offer a promising method to interrogate disease status and progression. In this work we have demonstrated a composite hydrogel-based sensing platform that may be used for optical detection of lactate. The sensor design consists of microsized enzymatic sensors that are embedded in an outer hydrogel matrix. In these engineered microdomains, encapsulated lactate oxidase serves as the bioactive component, phosphorescent metalloporphyrin acts as the optical transducer, and polyelectrolyte multilayers coated on the enzymatic microsensors control the permeation of lactate into the microsensors. The response of the composite hydrogel-based lactate sensors was characterized by subjecting the sensors to lactate concentration challenges at low physiological oxygen levels. The analytical range and the mean sensitivity were determined to be 9.2 ± 0.83 mg/dL and 11 ± 0.90% dL mg-1, respectively. Repeated cyclic exposure to high levels of lactate revealed that these sensors were extremely stable, with no significant loss in sensor response after 20 cycles. These preliminary results support the premise that these composite hydrogels are capable of continuous lactate tracking and have the potential for use as fully implantable optical lactate sensors.

Teslaphoresis of Carbon Nanotubes.

This paper introduces Teslaphoresis, the directed motion and self-assembly of matter by a Tesla coil, and studies this electrokinetic phenomenon using single-walled carbon nanotubes (CNTs). Conventional directed self-assembly of matter using electric fields has been restricted to small scale structures, but with Teslaphoresis, we exceed this limitation by using the Tesla coil's antenna to create a gradient high-voltage force field that projects into free space. CNTs placed within the Teslaphoretic (TEP) field polarize and self-assemble into wires that span from the nanoscale to the macroscale, the longest thus far being 15 cm. We show that the TEP field not only directs the self-assembly of long nanotube wires at remote distances (>30 cm) but can also wirelessly power nanotube-based LED circuits. Furthermore, individualized CNTs self-organize to form long parallel arrays with high fidelity alignment to the TEP field. Thus, Teslaphoresis is effective for directed self-assembly from the bottom-up to the macroscale.