Biodegradable electrohydraulic actuators for sustainable soft robots.

Combating environmental pollution demands a focus on sustainability, in particular from rapidly advancing technologies that are poised to be ubiquitous in modern societies. Among these, soft robotics promises to replace conventional rigid machines for applications requiring adaptability and dexterity. For key components of soft robots, such as soft actuators, it is thus important to explore sustainable options like bioderived and biodegradable materials. We introduce systematically determined compatible materials systems for the creation of fully biodegradable, high-performance electrohydraulic soft actuators, based on various biodegradable polymer films, ester-based liquid dielectric, and NaCl-infused gelatin hydrogel. We demonstrate that these biodegradable actuators reliably operate up to high electric fields of 200 V/µm, show performance comparable to nonbiodegradable counterparts, and survive more than 100,000 actuation cycles. Furthermore, we build a robotic gripper based on biodegradable soft actuators that is readily compatible with commercial robot arms, encouraging wider use of biodegradable materials systems in soft robotics.

Azetidine-based selective glycine transporter-1 (GlyT1) inhibitors with memory enhancing properties.

A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01-0.03 mg/kg.

Design of a High-Speed Prosthetic Finger Driven by Peano-HASEL Actuators.

Current designs of powered prosthetic limbs are limited by the nearly exclusive use of DC motor technology. Soft actuators promise new design freedom to create prosthetic limbs which more closely mimic intact neuromuscular systems and improve the capabilities of prosthetic users. This work evaluates the performance of a hydraulically amplified self-healing electrostatic (HASEL) soft actuator for use in a prosthetic hand. We compare a linearly-contracting HASEL actuator, termed a Peano-HASEL, to an existing actuator (DC motor) when driving a prosthetic finger like those utilized in multi-functional prosthetic hands. A kinematic model of the prosthetic finger is developed and validated, and is used to customize a prosthetic finger that is tuned to complement the force-strain characteristics of the Peano-HASEL actuators. An analytical model is used to inform the design of an improved Peano-HASEL actuator with the goal of increasing the fingertip pinch force of the prosthetic finger. When compared to a weight-matched DC motor actuator, the Peano-HASEL and custom finger is 10.6 times faster, has 11.1 times higher bandwidth, and consumes 8.7 times less electrical energy to grasp. It reaches 91% of the maximum range of motion of the original finger. However, the DC motor actuator produces 10 times the fingertip force at a relevant grip position. In this body of work, we present ways to further increase the force output of the Peano-HASEL driven prosthetic finger system, and discuss the significance of the unique properties of Peano-HASELs when applied to the field of upper-limb prosthetic design. This approach toward clinically-relevant actuator performance paired with a substantially different form-factor compared to DC motors presents new opportunities to advance the field of prosthetic limb design.

Design and Synthesis of Novel and Selective Glycine Transporter-1 (GlyT1) Inhibitors with Memory Enhancing Properties.

We report here the identification and optimization of a novel series of potent GlyT1 inhibitors. A ligand design campaign that utilized known GlyT1 inhibitors as starting points led to the identification of a novel series of pyrrolo[3,4- c]pyrazoles amides (21-50) with good in vitro potency. Subsequent optimization of physicochemical and in vitro ADME properties produced several compounds with promising pharmacokinetic profiles. In vivo inhibition of GlyT1 was demonstrated for select compounds within this series by measuring the elevation of glycine in the cerebrospinal fluid (CSF) of rats after a single oral dose of 10 mg/kg. Ultimately, an optimized lead, compound 46, demonstrated in vivo efficacy in a rat novel object recognition (NOR) assay after oral dosing at 0.1, 1, and 3 mg/kg.

Design and Synthesis of Novel and Selective Phosphodiesterase 2 (PDE2a) Inhibitors for the Treatment of Memory Disorders.

A series of potent and selective [1,2,4]triazolo[1,5-a]pyrimidine PDE2a inhibitors is reported. The design and improvement of the binding properties of this series was achieved using X-ray crystal structures in conjunction with careful analysis of electronic and structural requirements for the PDE2a enzyme. One of the lead compounds, compound 27 (DNS-8254), was identified as a potent and highly selective PDE2a enzyme inhibitor with favorable rat pharmacokinetic properties. Interestingly, the increased potency of compound 27 was facilitated by the formation of a halogen bond with the oxygen of Tyr827 present in the PDE2a active site. In vivo, compound 27 demonstrated significant memory enhancing effects in a rat model of novel object recognition. Taken together, these data suggest that compound 27 may be a useful tool to explore the pharmacology of selective PDE2a inhibition.