Resorbable barrier polymers for flexible bioelectronics.

Resorbable, implantable bioelectronic devices are emerging as powerful tools to reliably monitor critical physiological parameters in real time over extended periods. While degradable magnesium-based electronics have pioneered this effort, relatively short functional lifetimes have slowed clinical translation. Barrier films that are both flexible and resorbable over predictable timelines would enable tunability in device lifetime and expand the viability of these devices. Herein, we present a library of stereocontrolled succinate-based copolyesters which leverage copolymer composition and processing method to afford tunability over thermomechanical, crystalline, and barrier properties. One copolymer composition within this library has extended the functional lifetime of transient bioelectronic prototypes over existing systems by several weeks-representing a considerable step towards translational devices.

Anti-adhesive bioresorbable elastomer-coated composite hernia mesh that reduce intraperitoneal adhesions.

Intraperitoneal adhesions (IAs) are a major complication arising from abdominal repair surgeries, including hernia repair procedures. Herein, we fabricated a composite mesh device using a macroporous monofilament polypropylene mesh and a degradable elastomer coating designed to meet the requirements of this clinical application. The degradable elastomer was synthesized using an organo-base catalyzed thiol-yne addition polymerization that affords independent control of degradation rate and mechanical properties. The elastomeric coating was further enhanced by the covalent tethering of antifouling zwitterion molecules. Mechanical testing demonstrated the elastomer forms a robust coating on the polypropylene mesh does not exhibit micro-fractures, cracks or mechanical delamination under cyclic fatigue testing that exceeds peak abdominal loads (50 N/cm). Quartz crystal microbalance measurements showed the zwitterionic functionalized elastomer further reduced fibrinogen adsorption by 73% in vitro when compared to unfunctionalized elastomer controls. The elastomer exhibited degradation with limited tissue response in a 10-week murine subcutaneous implantation model. We also evaluated the composite mesh in an 84-day study in a rabbit cecal abrasion hernia adhesion model. The zwitterionic composite mesh significantly reduced the extent and tenacity of IAs by 94% and 90% respectively with respect to uncoated polypropylene mesh. The resulting composite mesh device is an excellent candidate to reduce complications related to abdominal repair through suppressed fouling and adhesion formation, reduced tissue inflammation, and appropriate degradation rate.

High-speed, scanned laser structuring of multi-layered eco/bioresorbable materials for advanced electronic systems.

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.

Shape Memory Behavior of Biocompatible Polyurethane Stereoelastomers Synthesized via Thiol-Yne Michael Addition.

Biodegradable shape memory elastomers have the potential for use in soft tissue engineering, drug delivery, and device fabrication applications. Unfortunately, few materials are able to meet the targeted degradation and mechanical properties needed for long-term implantable devices. In order to overcome these limitations, we have designed and synthesized a series of unsaturated polyurethanes that are elastic, degradable, and nontoxic to cells in vitro. The polymerization included a nucleophilic thiol-yne Michael addition between a urethane-based dipropiolate and a dithiol to yield an α,ß-unsaturated carbonyl moiety along the polymer backbone. The alkene stereochemistry of the materials was tuned between 32 and 82% cis content using a combination of an organic base and solvent polarity, which collectively direct the nucleophilic addition. The bulk properties such as tensile strength, modulus, and glass transition temperature can also be tuned broadly, and the hydrogen bonding imparted by the urethane moiety allows for these materials to elicit cyclic shape memory behavior. We also demonstrated that the in vitro degradation properties are highly dependent on the alkene stereochemistry.

Concomitant control of mechanical properties and degradation in resorbable elastomer-like materials using stereochemistry and stoichiometry for soft tissue engineering.

Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical, and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.

Zwitterion Surface-Functionalized Thermoplastic Polyurethane for Antifouling Catheter Applications.

Immobilizing zwitterionic molecules on material surfaces has been a promising strategy for creating antifouling surfaces. Herein, we show the ability to surface derivatize an allyl-ether-functionalized thermoplastic polyurethane (TPU) with a zwitterionic thiol in a radically induced thiol-ene reaction. The thermoplastic polyurethane was synthesized to have an allyl-ether side functionality using a modified chain extender molecule. The zwitterion surface functionalization was achieved via thiol-ene reaction in aqueous conditions. The presence of chemically tethered zwitterion moieties on the TPU surface was confirmed using X-ray photoelectron spectroscopy (XPS). Protein adsorption experiments via quartz crystal microbalance (QCM) show reduced fibrinogen attachment for the zwitterion-derivatized TPU when compared to its nonfunctionalized controls. The Zwitterion-TPU also showed a log scale reduction in bacterial adherence. For Pseudomonas aeruginosa and Staphylococcus epidermidis, the Zwitterion-TPU resulted in around a 40 and 50% lower bacterial biomass accumulation, respectively, over the time scale of the experiment. The fibroblast cell viability of TPU remained unaffected by functionalization with zwitterion thiol. The results from our model experiments suggest that a zwitterion-modified TPU is a promising candidate for antifouling catheters.

Zwitterionic amino acid-based Poly(ester urea)s suppress adhesion formation in a rat intra-abdominal cecal abrasion model.

Hernia repair outcomes have improved with more robust material options for surgeons and optimized surgical techniques. However, ventral hernia repairs remain challenging with an inherent risk of post-surgical adhesions in the peritoneal space which can occur regardless of interventional material or its surgical placement. Herein, amino acid-based poly(ester urea)s (PEUs) with varied amount of an allyl ether side chains were modified post polymerization modification with the zwitterionic sulfnate group (3-((3-((3-mercaptopropanoyl)oxy)propyl) dimethylammonio)propane-1-sulfonate) to promote anti-adhesive properties. These alloc-PEUs were processed using roll-to-roll fabrication methods to afford films that were amenable to surface functionalization via a zwitterion-thiol. Functional group availability on the surface was confirmed via fluorescence microscopy, x-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance (QCM) measurements. Zwitterionic treated PEUs exhibited reduced fibrinogen adsorption in vitro when compared to unfunctionalized control polymer. A rat intrabdominal cecal abrasion adhesion model was used to assess the extent and tenacity of adhesion formation in the presence of the PEUs. The 10% alloc-PEU zwitterion functionalized material was found to reduce the extent and tenacity of adhesions when compared to adhesion controls and the unfunctionalized PEU controls.

Post-fabrication QAC-functionalized thermoplastic polyurethane for contact-killing catheter applications.

The use of catheters is ubiquitous in medicine and the incidence of infection remains unacceptably high despite numerous advances in functional surfaces and drug elution. Herein we report the use of a thermoplastic polyurethane containing an allyl ether side-chain functionality (allyl-TPU) that allows for rapid and convenient surface modification with antimicrobial reagents, post-processing. This post-processing functionalization affords the ability to target appropriate TPU properties and maintain the functional groups on the surface of the device where they do not affect bulk properties. A series of quaternary ammonium thiol compounds (Qx-SH) possessing various hydrocarbon tail lengths (8-14 carbons) were synthesized and attached to the surface using thiol-ene "click" chemistry. A quantitative assessment of the amount of Qx-SH available on the surface was determined using fluorescence spectroscopy and X-ray photoelectron spectroscopy (XPS). Contact-killing assays note the Q8-SH composition has the highest antimicrobial activity, and a live/dead fluorescence assay reveals rapid contact-killing of Staphylococcus aureus (>75% in 5 min) and Escherichia coli (90% in 10 min) inocula. Scale-up and extrusion of allyl-TPU provides catheter prototypes for biofilm formation testing with Pseudomonas aeruginosa, and surface-functionalized catheters modified with Q8-SH demonstrate their ability to reduce biofilm formation.

The Quest of Excited-State Intramolecular Proton Transfer via Eight-Membered Ring π-Conjugated Hydrogen Bonding System.

Searching for eight-membered ring π-conjugated hydrogen bonding (8-MR H-bonding) systems with excited-state intramolecular proton transfer (ESIPT) property is seminal and synthetically challenging. In this work, a series of π-conjugated molecules (8-HB-1, 8-HB-L1 and 8-HB-2) potentially possessing 8-MR H-bonding are strategically designed, synthesized and characterized. The configurations of these three potential molecules are checked by their X-ray structures, among which 8-HB-L1 (a structurally locked 8-HB-1 core chromophore) is proved to be an 8-MR H-bonding system, whereas 8-HB-1 and 8-HB-2 are too sterically hindered to form the 8-MR intramolecular H-bond. The ESIPT property of 8-HB-L1 is confirmed by the dual fluorescence consisting of normal and proton-transfer tautomer emissions. The insight into the ESIPT process of 8-HB-L1 is provided by femtosecond fluorescence upconversion measurements together with computational simulation. The results demonstrate for the first time a successful synthetic route to attain the 8-MR H-bonding molecule 8-HB-L1 with ESIPT property.

The Excited-State Triple Proton Transfer Reaction of 2,6-Diazaindoles and 2,6-Diazatryptophan in Aqueous Solution.

3-Me-2,6-diazaindole ((2,6-aza)Ind) was strategically designed and synthesized to probe water molecule catalyzed excited-state proton transfer in aqueous solution. Upon electronic excitation (λmax ∼ 300 nm), (2,6-aza)Ind undergoes N(1)-H to N(6) long-distance proton transfer in neutral H2O, resulting in normal (340 nm) and proton-transfer tautomer (480 nm) emissions with an overall quantum yield of 0.25. The rate of the water-catalyzed proton transfer shows a prominent H/D kinetic isotope effect, which is determined to be 8.3 × 108 s-1 and 4.7 × 108 s-1 in H2O and D2O, respectively. Proton inventory experiments indicate the involvement of two water molecules and three protons, which undergo a relay type of excited-state triple proton transfer (ESTPT) in a concerted, asynchronous manner. The results demonstrate for the first time the fundamental of triple proton transfer in pure water for azaindoles as well as pave a new avenue for 2,6-diazatryptophan, an analogue of tryptophan exhibiting a similar ESTPT property with (2,6-aza)Ind, to probe biowaters in proteins.

N-H-Type Excited-State Proton Transfer in Compounds Possessing a Seven-Membered-Ring Intramolecular Hydrogen Bond.

A series of compounds containing 5-(2-aminobenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one (o-ABDI) as the core chromophore with a seven-membered-ring N-H-type intramolecular hydrogen bond have been synthesized and characterized. The acidity of the N-H proton and thus the hydrogen-bond strength can be fine-tuned by replacing one of the amino hydrogen atoms by a substituent R, the acidity increasing with increasing electron-withdrawing strength of R, that is, in the order H

New six- and seven-membered ring pyrrole-pyridine hydrogen bond systems undergoing excited-state intramolecular proton transfer.

New molecules, and , possessing six- and seven-membered ring pyrrole-pyridine hydrogen bonds, respectively, are designed and synthesized, which undergo excited-state intramolecular proton transfer with distinct reaction dynamics.

Locked ortho- and para-core chromophores of green fluorescent protein; dramatic emission enhancement via structural constraint.

We report the design strategy and synthesis of a structurally locked GFP core chromophore p-LHBDI, its ortho-derivative, o-LHBDI, and H2BDI possessing both para- and ortho-hydroxyl groups such that the inherent rotational motion of the titled compounds has been partially restricted. o-LHBDI possesses a doubly locked configuration, i.e., the seven-membered ring hydrogen bond and five-membered ring C(4-5-10-13-14) cyclization, from which the excited-state intramolecular proton transfer takes place, rendering a record high tautomer emission yield (0.18 in toluene) and the generation of amplified spontaneous emission. Compared with their unlocked counterparts, a substantial increase in the emission yield is also observed for p-LHBDI and H2BDI in anionic forms in water, and accordingly the structure versus luminescence relationship is fully discussed based on their chemistry and spectroscopy aspect. In solid, o-LHBDI exhibits an H-aggregate-like molecular packing, offers narrow-bandwidth emission, and has been successfully applied to fabricate a yellow organic light emitting diodes (λmax = 568 nm, ηext = 1.9%) with an emission full width at half-maximum as narrow as 70 nm.