Publications by authors named "Christopher J Bettinger"

Intestinal retentive devices (IRDs) are devices designed to anchor within the lumen of the intestines for long-term residence in the gastrointestinal tract. IRDs can enable impactful medical device technologies including sustained oral drug delivery systems, indwelling sensors, or real-time diagnostics. The design and testing of IRDs present a myriad of challenges, including precise deployment of the device at desired intestinal locations, secure anchoring within the gastrointestinal tract to allow for natural function, and safe removal of the IRD at user-defined times.

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Miniature wireless bioelectronic implants that can operate for extended periods of time can transform how we treat disorders by acting rapidly on precise nerves and organs in a way that drugs cannot. To reach this goal, materials and methods are needed to wirelessly transfer energy through the body or harvest energy from the body itself. We review some of the capabilities of emerging energy transfer methods to identify the performance envelope for existing technology and discover where opportunities lie to improve how much-and how efficiently-we can deliver energy to the tiny bioelectronic implants that can support emerging medical technologies.

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The potential of ingestible medical devices can be greatly enhanced through the use of smart structures made from stimuli-responsive materials. While hydration is a convenient stimulus for inducing shape changes in biomaterials, finding robust materials that can achieve rapid actuation, facile manufacturability, and biocompatibility suitable for ingestible medical devices poses practical challenges. Hydration is a convenient stimulus to induce shape changes in smart biomaterials; however, there are many practical challenges to identifying materials that can achieve rapid actuation and facile manufacturability while satisfying constraints associated with biocompatibility requirements and mechanical properties that are suitable for ingestible medical devices.

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Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain devices in the small intestine primarily focus on chemical anchoring using mucoadhesives or mechanical coupling using expandable devices or structures that pierce the intestinal epithelium. Here, the feasibility of intestinal retention using devices containing villi-inspired structures that mechanically interlock with natural villi of the small intestine is evaluated.

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Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited.

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Hydrogels are promising materials for soft and implantable strain sensors owing to their large compliance (<100 kPa) and significant extensibility (ε >500%) compared to other polymer networks. Further, hydrogels can be functionalized to seamlessly integrate with many types of tissues. However, most current methods attempt to imbue additional electronic functionality to structural hydrogel materials by incorporating fillers with orthogonal properties such as electronic or mixed ionic conduction.

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Ionically conductive hydrogels are gaining traction as sensing and structural materials for use bioelectronic devices. Hydrogels that feature large mechanical compliances and tractable ionic conductivities are compelling materials that can sense physiological states and potentially modulate the stimulation of excitable tissue because of the congruence in electro-mechanical properties across the tissue-material interface. However, interfacing ionic hydrogels with conventional DC voltage-based circuits poses several technical challenges including electrode delamination, electrochemical reaction, and drifting contact impedance.

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Low-profile and transient ingestible electronic capsules for diagnostics and therapeutics can replace widely used yet invasive procedures such as endoscopies. Several gastrointestinal diseases such as reflux disease, Crohn's disease, irritable bowel syndrome, and eosinophilic esophagitis result in increased intercellular dilation in epithelial barriers. Currently, the primary method of diagnosing and monitoring epithelial barrier integrity is via endoscopic tissue biopsies followed by histological imaging.

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Designing bioelectronic devices that seamlessly integrate with the human body is a technological pursuit of great importance. Bioelectronic medical devices that reliably and chronically interface with the body can advance neuroscience, health monitoring, diagnostics, and therapeutics. Recent major efforts focus on investigating strategies to fabricate flexible, stretchable, and soft electronic devices, and advances in materials chemistry have emerged as fundamental to the creation of the next generation of bioelectronics.

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The minimally invasive treatment of intracranial aneurysms by endovascular coiling is attractive yet faces challenges related to the degradation of fibrin clots in the aneurysm sac over time. Fibrin gels cross-linked with genipin exhibit enhanced mechanical and chemical stability, but there are many unknowns related to best practices for delivery from endovascular devices and subsequent integration of cross-linkers with the nascent clot. Here, we describe the characterization of genipin-eluting polymer fibers prepared by coextrusion with poly(ethylene--vinyl acetate).

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Implantable neural interfaces are important tools to accelerate neuroscience research and translate clinical neurotechnologies. The promise of a bidirectional communication link between the nervous system of humans and computers is compelling, yet important materials challenges must be first addressed to improve the reliability of implantable neural interfaces. This perspective highlights recent progress and challenges related to arguably two of the most common failure modes for implantable neural interfaces: (1) compromised barrier layers and packaging leading to failure of electronic components; (2) encapsulation and rejection of the implant due to injurious tissue-biomaterials interactions, which erode the quality and bandwidth of signals across the biology-technology interface.

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Soft materials that contain dynamic and reversible bonds exhibit unique properties including unusual extensibility, reversible elasticity, and self-healing capabilities, for example. Catechol motifs are of particular interest owing to their ability to form many kinds of reversible bonds; however, there are few reports on the role of hydrogen bonds between catechols. Here, physically crosslinked self-assembled networks composed of catechol-functionalized ABA triblock co-polymers are synthesized and characterized to elucidate the role of intermolecular bonding between catechol motifs on bulk mechanical properties.

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The inflammatory brain tissue response to implanted neural electrode devices has hindered the longevity of these implants. Zwitterionic polymers have a potent anti-fouling effect that decreases the foreign body response to subcutaneous implants. In this study, we developed a nanoscale anti-fouling coating composed of zwitterionic poly (sulfobetaine methacrylate) (PSB) and polydopamine (PDA) for neural probes.

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Catechol-bearing polymers form hydrogel networks through cooperative oxidative crosslinking and coordination chemistry. Here we describe the kinetics of cation-dependent electrochemical-mediated gelation of precursor solutions composed of catechol functionalized four-arm poly(ethylene glycol) combined with select metal cations. The gelation kinetics, mechanical properties, crosslink composition, and self-healing capacity is a strong function of the valency and redox potential of metal ions in the precursor solution.

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Polydopamine is a versatile and organic material that can be deposited as a conformal film with nanometer thickness on virtually any substrate. Much of the initial foundational work regarding polydopamine synthesis and processing was reported during the 2000s. Latter years have witnessed increasing interest and widespread adoption of polydopamine as a material for many applications including medicine.

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Ingestible biomedical devices that diagnose, prevent, or treat diseases has been a dream of engineers and clinicians for decades. The increasing apparent importance of gut health on overall well-being and the prevalence of many gastrointestinal diseases have renewed focus on this emerging class of medical devices. Several prominent examples of commercially successful ingestible medical devices exist.

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Peripheral nerve interfaces are a central technology in advancing bioelectronic medicines because these medical devices can record and modulate the activity of nerves that innervate visceral organs. Peripheral nerve interfaces that use electrical signals for recording or stimulation have advanced our collective understanding of the peripheral nervous system. Furthermore, devices such as cuff electrodes and multielectrode arrays of various form factors have been implanted in the peripheral nervous system of humans in several therapeutic contexts.

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Self-assembled mechanically robust Dopa-bearing triblock copolymer networks improve underwater adhesion through both energy dissipation and interfacial bonding. Polymer networks that incorporate energy dissipating motifs could improve the performance of high-performance wet adhesives rather than only by interfacial bonds.

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The conformal nature of in situ polymerization of adhesive dopamine molecules permits the strong underwater adhesion between polydopamine (PDA) nanomembranes and the target substrates. However, the adhesive interaction between the postdeposit PDA nanomembranes and other macrobodies is strongly influenced by the texture of PDA nanomembranes. Here we report the texture-dependent adhesion of PDA nanomembranes both in air and aqueous environments.

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Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments.

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Stimulus-responsive hydrogels make up an important class of programmable materials for a wide range of biomedical applications. Ultrasound (US) is a stimulus that offers utility because of its ability to permeate tissue and rapidly induce chemical alterations in aqueous media. Here we report on the synthesis and US-mediated disintegration of stimulus-responsive telechelic Dopa-modified polyethylene glycol-based hydrogels.

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The facile preparation of conformal polydopamine (PDA) films on broad classes of materials has prompted extensive research into a wide variety of potential applications for PDA. The constituent molecular species in PDA exhibit diverse chemical moieties, and therefore highly variable properties of PDA-based devices may evolve with post-processing conditions. Here we report the use of redox-inactive cations for oxidative post-processing of deposited PDA films.

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The elevated infection rise associated with indwelling devices can compromise the performance of percutaneous devices and increase the risk of complications. High infection rates are associated with both the high bacterial load on the skin and epidermal downgrowth at the interface of the indwelling material. Here, we propose a drug-eluting material that promotes local dermal regeneration to reduce epidermal downgrowth.

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Temperature dependent thermal conductivities and thermal interface resistances of pentacene (Pn) thin films deposited on silicon substrates and self-assembled monolayer-modified [octadecyltrichlorosilane (OTS) and (3-aminopropyl)triethoxysilane (APTES)] silicon substrates were measured using frequency domain thermoreflectance. Atomic force microscopy images were used to derive an effective film thickness for thermal transport that accounts for surface roughness. Data taken over a temperature range of 77-300 K for various morphologies and film thicknesses show that the thermal conductivity increases with increasing Pn grain size.

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