Chemical upcycling of commodity thermoset polyurethane foams towards high-performance 3D photo-printing resins.

Polyurethane thermosets are indispensable to modern life, but their widespread use has become an increasingly pressing environmental burden. Current recycling approaches are economically unattractive and/or lead to recycled products of inferior properties, making their large-scale implementation unviable. Here we report a highly efficient chemical strategy for upcycling thermoset polyurethane foams that yields products of much higher economic values than the original material. Starting from a commodity foam, we show that the polyurethane network is chemically fragmented into a dissolvable mixture under mild conditions. We demonstrate that three-dimensional photo-printable resins with tunable material mechanical properties-which are superior to commercial high-performance counterparts-can be formulated with the addition of various network reforming additives. Our direct upcycling of commodity foams is economically attractive and can be implemented with ease, and the principle can be expanded to other commodity thermosets.

Peptidoglycan-inspired autonomous ultrafast self-healing bio-friendly elastomers for bio-integrated electronics.

Elastomers are essential for stretchable electronics, which have become more and more important in bio-integrated devices. To ensure high compliance with the application environment, elastomers are expected to resist, and even self-repair, mechanical damage, while being friendly to the human body. Herein, inspired by peptidoglycan, we designed the first room-temperature autonomous self-healing biodegradable and biocompatible elastomers, poly(sebacoyl 1,6-hexamethylenedicarbamate diglyceride) (PSeHCD) elastomers. The unique structure including alternating ester-urethane moieties and bionic hybrid crosslinking endowed PSeHCD elastomers superior properties including ultrafast self-healing, tunable biomimetic mechanical properties, facile reprocessability, as well as good biocompatibility and biodegradability. The potential of the PSeHCD elastomers was demonstrated as a super-fast self-healing stretchable conductor (21 s) and motion sensor (2 min). This work provides a new design and synthetic principle of elastomers for applications in bio-integrated electronics.

Self-healing polyurethane-elastomer with mechanical tunability for multiple biomedical applications in vivo.

The unique properties of self-healing materials hold great potential in the field of biomedical engineering. Although previous studies have focused on the design and synthesis of self-healing materials, their application in in vivo settings remains limited. Here, we design a series of biodegradable and biocompatible self-healing elastomers (SHEs) with tunable mechanical properties, and apply them to various disease models in vivo, in order to test their reparative potential in multiple tissues and at physiological conditions. We validate the effectiveness of SHEs as promising therapies for aortic aneurysm, nerve coaptation and bone immobilization in three animal models. The data presented here support the translation potential of SHEs in diverse settings, and pave the way for the development of self-healing materials in clinical contexts.

Mechanically and biologically skin-like elastomers for bio-integrated electronics.

The bio-integrated electronics industry is booming and becoming more integrated with biological tissues. To successfully integrate with the soft tissues of the body (eg. skin), the material must possess many of the same properties including compliance, toughness, elasticity, and tear resistance. In this work, we prepare mechanically and biologically skin-like materials (PSeD-U elastomers) by designing a unique physical and covalent hybrid crosslinking structure. The introduction of an optimal amount of hydrogen bonds significantly strengthens the resultant elastomers with 11 times the toughness and 3 times the strength of covalent crosslinked PSeD elastomers, while maintaining a low modulus. Besides, the PSeD-U elastomers show nonlinear mechanical behavior similar to skins. Furthermore, PSeD-U elastomers demonstrate the cytocompatibility and biodegradability to achieve better integration with tissues. Finally, piezocapacitive pressure sensors are fabricated with high pressure sensitivity and rapid response to demonstrate the potential use of PSeD-U elastomers in bio-integrated electronics.

A Highly Efficient Self-Healing Elastomer with Unprecedented Mechanical Properties.

It is highly desirable, although very challenging, to develop self-healable materials exhibiting both high efficiency in self-healing and excellent mechanical properties at ambient conditions. Herein, a novel Cu(II)-dimethylglyoxime-urethane-complex-based polyurethane elastomer (Cu-DOU-CPU) with synergetic triple dynamic bonds is developed. Cu-DOU-CPU demonstrates the highest reported mechanical performance for self-healing elastomers at room temperature, with a tensile strength and toughness up to 14.8 MPa and 87.0 MJ m-3 , respectively. Meanwhile, the Cu-DOU-CPU spontaneously self-heals at room temperature with an instant recovered tensile strength of 1.84 MPa and a continuously increased strength up to 13.8 MPa, surpassing the original strength of all other counterparts. Density functional theory calculations reveal that the coordination of Cu(II) plays a critical role in accelerating the reversible dissociation of dimethylglyoxime-urethane, which is important to the excellent performance of the self-healing elastomer. Application of this technology is demonstrated by a self-healable and stretchable circuit constructed from Cu-DOU-CPU.

A biodegradable functional water-responsive shape memory polymer for biomedical applications.

Shape memory polymers (SMPs) have exhibited great potential in biomedical applications. However, the typical triggers of shape recovery such as heat, UV light, and electricity may be harmful to humans. Accordingly, water-responsive SMPs have become significant, especially for in vivo applications, due to the intrinsic biocompatibility and ready availability of water. However, the reported water-responsive SMPs are limited and relatively complicated. Here, we design a new water-responsive SMP, poly(butanetetrol fumarate) (PBF); the properties of PBF could be modulated by curing. The cured PBF scaffolds exhibited high shape recovery and fixity rates (>95%). PBF showed good biodegradability, and it could support the attachment, viability and alkaline phosphatase activity of osteoblasts. Furthermore, PBF could be readily functionalized via pendant hydroxyl groups, which was demonstrated by the immobilization and controlled release of bone morphogenetic protein 2. We expect that PBF will be useful for various biomedical applications including water-responsive scaffolds, sensors or actuators.

A poly(glycerol sebacate) based photo/thermo dual curable biodegradable and biocompatible polymer for biomedical applications.

Due to its biomimetic mechanical properties to soft tissues, excellent biocompatibility and biodegradability, poly (glycerol sebacate) (PGS) has emerged as a representative bioelastomer and been widely used in biomedical engineering. However, the typical curing of PGS needs high temperature (>120 °C), high vacuum (>1 Torr), and long duration (>12 h), which limit its further applications. Accordingly, we designed, synthesized and characterized a photo/thermo dual curable polymer based on PGS. Treatment of PGS with 2-isocyanatoethyl methacrylate without additional reagents readily produced a methacrylated PGS (PGS-IM). Photo-curing of PGS-IM for 10 min at room temperature using salt leaching method efficiently produced porous scaffolds with a thickness up to 1 mm. PGS-IM was adapt to thermo-curing as well. The combination of photo and thermo curing provided a further way to modulate the properties of resultant porous scaffolds. Interestingly, photo-cured scaffolds exhibited hierarchical porous structures carrying extensive micropores with a diameter from several to hundreds micrometers. All the scaffolds showed good elasticity and biodegradability. In addition, PGS-IM exhibited good compatibility with L929 fibroblast cells. We expect this new PGS based biomaterial will have a wide range of biomedical applications.

Miniature amperometric self-powered continuous glucose sensor with linear response.

Continuous glucose measurement has improved the treatment of type 1 diabetes and is typically provided by externally powered transcutaneous amperometric sensors. Self-powered glucose sensors (SPGSs) could provide an improvement over these conventionally powered devices, especially for fully implanted long-term applications where implanted power sources are problematic. Toward this end, we describe a robust SPGS that may be built from four simple components: (1) a low-potential, wired glucose oxidase anode; (2) a Pt/C cathode; (3) an overlying glucose flux-limiting membrane; and (4) a resistor bridging the anode and cathode. In vitro evaluation showed that the sensor output is linear over physiologic glucose concentrations (2-30 mM), even at low O(2) concentrations. Output was independent of the connecting resistor values over the range from 0 to 10 MΩ. The output was also stable over 60 days of continuous in vitro operation at 37 °C in 30 mM glucose. A 5-day trial in a volunteer demonstrated that the performance of the device was virtually identical to that of a conventional amperometric sensor. Thus, this SPGS is an attractive alternative to conventionally powered devices, especially for fully implanted long-term applications.

Metabolic biofouling of glucose sensors in vivo: role of tissue microhemorrhages.

OBJECTIVE: Based on our in vitro study that demonstrated the adverse effects of blood clots on glucose sensor function, we hypothesized that in vivo local tissue hemorrhages, induced as a consequence of sensor implantation or sensor movement post-implantation, are responsible for unreliable readings or an unexplained loss of functionality shortly after implantation. RESEARCH DESIGN AND METHODS: To investigate this issue, we utilized real-time continuous monitoring of blood glucose levels in a mouse model. Direct injection of blood at the tissue site of sensor implantation was utilized to mimic sensor-induced local tissue hemorrhages. RESULTS: It was found that blood injections, proximal to the sensor, consistently caused lowered sensor glucose readings, designated temporary signal reduction, in vivo in our mouse model, while injections of plasma or saline did not have this effect. CONCLUSION: These results support our hypothesis that tissue hemorrhage and resulting blood clots near the sensor can result in lowered local blood glucose concentrations due to metabolism of glucose by the clot. The lowered local blood glucose concentration led to low glucose readings from the still functioning sensor that did not reflect the systemic glucose level.

Importance of interleukin-1 and interleukin-1 receptor antagonist in short-term glucose sensor function in vivo.

BACKGROUND: The importance of the interleukin (IL)-1 cytokine family in inflammation and immunity is well established as a result of extensive in vitro and in vivo studies. In fact, much of our understanding of the in vivo importance of interleukin-1beta (IL-1B) is the result of research utilizing transgenic mice, such as overexpression or deficiencies of the naturally occurring inhibitor of IL-1 known as interleukin-1 receptor antagonist (IL-1RA). For the present studies, we utilized these transgenic mice to determine the role of IL-1B in glucose sensor function in vivo. METHODS: To investigate the role of IL-1B in glucose sensor function in vivo, we compared glucose sensor function in trans-genic mice that (1) overexpressed IL-1RA [B6.Cg-Tg(II1rn)1Dih/J] and (2) are deficient in IL-1RA (B6.129S-Il1rn(tm1Dih)/J), with mice that have normal levels of IL-1RA (C57BL/6). RESULTS: Our studies demonstrated that, during the first 7 days post-sensor implantation (PSI), mice deficient in IL-1RA had extensive inflammation and decreased sensor function when compared to normal or IL-1RA-overexpressing mice. CONCLUSION: These data directly support our hypothesis that the IL-1 family of cytokines and antagonists play a critical role in controlling tissue reactions and thereby sensor function in vivo during the first 7 days PSI.

Blood-induced interference of glucose sensor function in vitro: implications for in vivo sensor function.

BACKGROUND: Although tissue hemorrhages, with resulting blood clots, are associated with glucose sensor implantation, virtually nothing known is about the impact of red blood cells and red blood cell clots on sensor function in vitro or in vivo. In these studies, we tested the hypothesis that blood can directly interfere with glucose sensor function in vitro. METHODS: To test this hypothesis, heparinized human whole blood (HWB) and nonheparinized human whole blood (WB) were obtained from normal individuals. Aliquots of HWB and WB samples were also fractionated into plasma, serum, and total leukocyte (TL) components. Resulting HWB, WB, and WB components were incubated in vitro with an amperometric glucose sensor for 24 hours at 37 degrees C. During incubation, blood glucose levels were determined periodically using a glucose monitor, and glucose sensor function (GSF) was monitored continuously as nanoampere output. RESULTS: Heparinized human whole blood had no significant effect on GSF in vitro, nor did TL, serum, or plasmaderived clots from WB. Sensors incubated with WB displayed a rapid signal loss associated with clot formation at 37 degrees C. The half-life was 0.8 +/- 0.2 hours (n = 16) for sensors incubated with WB compared to 3.2 +/- 0.5 (n = 12) for sensors incubated with HWB with a blood glucose level of approximately 100 mg/dl. CONCLUSIONS: These studies demonstrated that human whole blood interfered with GSF in vitro. These studies further demonstrated that this interference was related to blood clot formation, as HWB, serum, plasma-derived clots, or TL did not interfere with GSF in vitro in the same way that WB did. These in vitro studies supported the concept that the formation of blood clots at sites of glucose sensor implantation could have a negative impact on GSF in vivo.

Continuous glucose monitoring in normal mice and mice with prediabetes and diabetes.

It is well established that the key to minimizing diabetes-associated complications, in both type 1 and type 2 diabetes, is tight regulation of blood glucose levels. Currently the major approach to regulating blood glucose levels in patients with diabetes relies on external blood glucose monitors. However, poor patient compliance usually results in limited insights into the dynamic range of blood glucose levels (i.e., hyperglycemia vs. hypoglycemia), and inadequate prediction and control of blood glucose levels in these patients. Implantable glucose sensors hold promise for controlling blood glucose levels, but currently these sensors have only limited in vivo life span. Recently we have developed an extremely robust murine model for implantable glucose sensors. In the present study, we have extended this model by developing a complete system for real-time continuous glucose monitoring in normal mice and mice with prediabetes and diabetes (type 1). These studies demonstrated that (1) glucose sensors can be implanted and maintained subcutaneously in the mice; (2) continuous glucose sensor data can be obtained for at least 5 days; and (3) subcutaneous blood glucose sensing paralleled blood glucose levels in normal mice and mice with prediabetes and diabetes. Subcutaneous blood glucose sensing also successfully tracked changes in blood glucose levels induced in the mice with diabetes by administration of oral glucose or insulin. These results mirror the results for subcutaneous blood glucose sensing seen in both normal subjects and patients with diabetes, and therefore validate both our continuous glucose monitoring system in the mouse, and the use of the mouse as a model for implantable glucose sensing in vivo.