Tethering zwitterionic polymer coatings to mediated glucose biosensor enzyme electrodes can decrease sensor foreign body response yet retain sensor sensitivity to glucose.

Foreign body response (FBR) is a major challenge that affects implantable biosensors and medical devices, including glucose biosensors, leading to a deterioration in device response over time. Polymer shields are often used to mitigate this issue. Zwitterionic polymers (ZPs) are a promising class of materials that reduce biofouling of implanted devices. A series of ZPs each containing tetherable epoxide functional groups was synthesised for application as a polymer shield for eventual application as implantable glucose biosensors. The polymer shields were initially tested for the ability to resist fibrinogen adsorption and fibroblast adhesion. All synthesised ZPs showed comparable behaviour to a commercial Lipidure ZP in resisting fibrinogen adsorption. Nafion, a common anionic shield used against electrochemical interferents, showed higher protein adsorption and comparable cell adhesion resistance as uncoated control surfaces. However, a poly(2-methacryloyloxyethyl phosphorylcholine-co-glycidyl methacrylate) (MPC)-type ZP showed similar behaviour to Lipidure, with approximately 50% reduced fibrinogen adsorption and 80% decrease in fibroblast adhesion compared to uncoated controls. An MPC-coated amperometric glucose biosensor showed comparable current density and a 1.5-fold increase in sensitivity over an uncoated control biosensor, whereas all other polymer shields tested, including Lipidure, Nafion and a poly(ethyleneglycol) polymer, resulted in lower sensitivity and current density. Collectively, these characteristics make MPC-polymer shield coatings an appealing possibility for use in implantable glucose sensors and other implanted devices with the aim of reducing FBR while maintaining sensor performance.

Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform.

Fibrous capsule (FC) formation, secondary to the foreign body response (FBR), impedes molecular transport and is detrimental to the long-term efficacy of implantable drug delivery devices, especially when tunable, temporal control is necessary. We report the development of an implantable mechanotherapeutic drug delivery platform to mitigate and overcome this host immune response using two distinct, yet synergistic soft robotic strategies. Firstly, daily intermittent actuation (cycling at 1 Hz for 5 minutes every 12 hours) preserves long-term, rapid delivery of a model drug (insulin) over 8 weeks of implantation, by mediating local immunomodulation of the cellular FBR and inducing multiphasic temporal FC changes. Secondly, actuation-mediated rapid release of therapy can enhance mass transport and therapeutic effect with tunable, temporal control. In a step towards clinical translation, we utilise a minimally invasive percutaneous approach to implant a scaled-up device in a human cadaveric model. Our soft actuatable platform has potential clinical utility for a variety of indications where transport is affected by fibrosis, such as the management of type 1 diabetes.

Degradable Glycopolyester-like Nanoparticles by Radical Ring-Opening Polymerization.

A small library of degradable polyester-like glycopolymers was successfully prepared by the combination of radical ring-opening copolymerization of 2-methylene-1,3-dioxepane as a cyclic ketene acetal (CKA) with vinyl ether (VE) derivatives and a Pd-catalyzed thioglycoconjugation. The resulting thioglycopolymers were formulated into self-stabilized thioglyconanoparticles, which were stable up to 4 months and were enzymatically degraded. Nanoparticles and their degradation products exhibited a good cytocompatibility on two healthy cell lines. Interactions between thioglyconanoparticles and lectins were investigated and highlighted the presence of both specific carbohydrate/lectin interactions and nonspecific hydrophobic interactions. Fluorescent thioglyconanoparticles were also prepared either by encapsulation of Nile red or by the functionalization of the polymer backbone with rhodamine B. Such nanoparticles were used to prove the cell internalization of the thioglyconanoparticles by lung adenocarcinoma (A549) cells, which underlined the great potential of P(CKA-co-VE) copolymers for biomedical applications.

Medical devices, smart drug delivery, wearables and technology for the treatment of Diabetes Mellitus.

Diabetes mellitus refers to a group of metabolic disorders which affect how the body uses glucose impacting approximately 9% of the population worldwide. This review covers the most recent technological advances envisioned to control and/or reverse Type 1 diabetes mellitus (T1DM), many of which will also prove effective in treating the other forms of diabetes mellitus. Current standard therapy for T1DM involves multiple daily glucose measurements and insulin injections. Advances in glucose monitors, hormone delivery systems, and control algorithms generate more autonomous and personalised treatments through hybrid and fully automated closed-loop systems, which significantly reduce hypo- and hyperglycaemic episodes and their subsequent complications. Bi-hormonal systems that co-deliver glucagon or amylin with insulin aim to reduce hypoglycaemic events or increase time spent in target glycaemic range, respectively. Stimuli responsive materials for the controlled delivery of insulin or glucagon are a promising alternative to glucose monitors and insulin pumps. By their self-regulated mechanism, these "smart" drugs modulate their potency, pharmacokinetics and dosing depending on patients' glucose levels. Islet transplantation is a potential cure for T1DM as it restores endogenous insulin and glucagon production, but its use is not yet widespread due to limited islet sources and risks of chronic immunosuppression. New encapsulation strategies that promote angiogenesis and oxygen delivery while protecting islets from recipients' immune response may overcome current limiting factors.

Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes.

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long-term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D. In this progress report, the design considerations and functional requirements of macroencapsulation systems are reviewed, specifically for stem-cell derived islets (SC-islets), highlighting distinct design parameters. Additionally, a perspective on the future for macroencapsulation systems is given, and how incorporating continuous sensing and closed-loop feedback can be transformative in advancing toward an autonomous biohybrid artificial pancreas.