Urethane Urea Research Articles

Evaluation of Gelatin-Based Poly(Ester Urethane Urea) Electrospun Fibers Using Human Mesenchymal and Neural Stem Cells.

Previously, a new biodegradable poly(ester urethane urea) was synthesized based on polycaprolactone-diol and fish gelatin (PU-Gel). In this work, the potential of this new material for neural tissue engineering is evaluated. Membranes with randomly oriented fibers and with aligned fibers are produced using electrospinning and characterized regarding their mechanical behavior under both dry and wet conditions. Wet samples exhibit a lower Young's modulus than dry ones and aligned membranes are stiffer and more brittle than those randomly oriented. Cyclic tensile tests are conducted and high values for recovery ratio and resilience are obtained. Both membranes exhibited a hydrophobic surface, measured by the water contact angle (WCA). Human mesenchymal stem cells from umbilical cord tissue (UC-MSCs) and human neural stem cells (NSCs) are seeded on both types of membranes, which support their adhesion and proliferation. Cells stained for the cytoskeleton and nucleus in membranes with aligned fibers display an elongated morphology following the alignment direction. As the culture time increased, higher cell viability is obtained on randomfibers for UC-MSCs while no differences are observed for NSCs. The membranes support neuronal differentiation of NSCs, as evidenced by markers for a neuronal filament protein (NF70) and for a microtubule-associated protein (MAP2).

Programming degradation and closed-loop recycling of ultra-stable bio-based thermosetting polyurethane relied on double-locked covalent adaptable networks

Castor oil (CO) derived thermoset polyurethanes are usually limited by their poor mechanical properties and the difficulty in removing or recycling because of the aliphatic or alicyclic backbone and their permanent cross-linking structures. Although covalent adaptable networks (CANs) based on dynamic bonds have been proposed, it is still highly desired to fabricate polymer CANs with high performance, stimulus resistance, stepwise degradation and closed-loop recycling from renewable CO for sustainable development. In this study, CO-based poly(urethane urea) (PU) thermosets relied on double-locked covalent adaptable networks (DLCANs) were proposed to achieve programmable degradation and closed-loop recycling. From a CO-derived isocyanate monomers and two dynamic curing agents of aminophenyl disulfide (AFDS) and aminophenyl diimine (AFDI), bio-based thermosets of PU DLCANs were prepared. The bio-based PU DLCANs were ultra-stable and still kept cross-linked upon disadvantageous chemical stimuli instead of dissociating like the conventional CANs. Moreover, the bio-based PU DLCANs became degradable only by applying programmed stimuli, when the two types of dynamic cross-links in parallel connection were both broken step by step. Meanwhile, the broken cross-links could be reformed when dynamic bonds regenerated upon heating, leading to the closed-loop recycling of the bio-based PU DLCANs. Besides, being applied as coatings, the bio-based PU DLCANs exhibited UV shielding, self-healing properties and long-term stability as well as programming removable properties. The bio-based thermosets relied on DLCANs have the potential to guarantee the reliability of polymeric CANs and maintain the closed-loop recycling by applying programmable stimuli, which is quite meaningful and practical for life-time environmental-friendly coatings.

Zwitterionic modification: A strategy to enhance the mechanical properties, lubricity and hemo- and biocompatibility of silicone poly(carbonate urethane urea)

Incorporating zwitterions into the blood-contacting materials has been demon-strated an effective and convenient strategy to minimize protein adsorption and platelet deposition, but is frequently detrimental to the mechanical properties. Herein a feeding 29.0 mol% sulfobetaine (SB) siloxane poly(carbonate urethane urea) (SSiPCUU) was synthesized and evaluated. Although the equilibrium water uptake ratio was increased to 1.20% markedly depressing the hydrolytic degradation resistance and mechanical properties after the zwitterionic modification, its maximum tensile stress and tear strength in the wet state still kept the highest among all the tested samples because the urea groups created therefrom gave rise to the formation of bifurcating hydrogen bonds making a significant contribution to the mechanical properties alongside the unique ion clusters formed from pendant SB species. As a consequence of zwitterionic incorporation, it exhibited an extremely low friction coefficient indicating an excellent lubricity in a wet environment without any post-treatment. Accordingly, both the nonspecific protein adsorption and platelet adhesion were evidently decreased. Moreover, it also depicted a good transparency. The high lubrication performance is desirable for lessening the damage to human blood vessels and a good transparency is favorable to the visualization of the flow of liquid in the catheter. These results illustrated the great potential of the zwitterionic SSiPCUU used in the preparation of balloon catheters, artificial blood vessels, stent coverings and other blood-contacting medical implants and devices.

Redefining vascular repair: revealing cellular responses on PEUU-gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models.

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0cm and a length of 11cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

4D-Printed Tool for Compressing a Shape Memory Polyurethane Foam during Programming.

Although several force application concepts are known that can be used to deform shape memory polymers (SMPs) within the scope of programming, controlled deformation is challenging in the case of samples with a cylinder-like shape, which need to be homogeneously compressed starting from the lateral surface. To solve this problem, this contribution follows a material approach that takes advantage of four-dimensional (4D) printing. Fused filament fabrication (FFF) was used as an additive manufacturing (AM) technique to produce a thermoresponsive tool in a cylindrical shape from a polyether urethane (PEU) having a glass transition temperature (Tg) close to 55 °C, as determined by differential scanning calorimetry (DSC). Once it was 4D-printed, a sample of laser cut polyester urethane urea (PEUU) foam with a cylindrical wall was placed inside of it. Subsequent heating to 75 °C and keeping that temperature constant for 15 min resulted in the compression of the foam, because the internal stresses of the PEU were transferred to the PEUU, whose soft segments were completely molten at 65 °C as verified by DSC. Upon cooling to -15 °C and thus below the offset temperature of the soft segment crystallization transition of the PEUU, the foam was fixed in its new shape. After 900 days of storage at temperatures close to 23 °C, the foam recovered its original shape upon reheating to 75 °C. In another experiment, a 4D-printed cylinder was put into hibernation for 900 days before its thermoresponsiveness was investigated. In the future, 4D-printed tools may be produced in many geometries, which fit well to the shapes of the SMPs to be programmed. Beyond programming SMP foams, transferring the forces released by 4D-printed tools to other programmable materials can further expand technical possibilities.

Chemical and Physical Debonding-on-Demand of Poly(urethane urea) Thermoset Adhesives to Facilitate the Recycling of Engineered Wooden Products

Chemical and Physical Debonding-on-Demand of Poly(urethane urea) Thermoset Adhesives to Facilitate the Recycling of Engineered Wooden Products

Electrospun membranes of diselenide-containing poly(ester urethane)urea for in situ catalytic generation of nitric oxide

Nitric oxide (NO) plays an important role as a signalling molecule in the biological system. Organoselenium-coated or grafted biomaterials have the potential to achieve controlled NO release as they can catalyse decomposition of endogenous S-nitrosothiols to NO. However, such biomaterials are often challenged by the loss of the catalytic sites, which can affect the stability in tissue repair applications. In this work, we prepare a diselenide-containing poly(ester urethane)urea (SePEUU) polymer with Se–Se in the backbone, which is further electrospun into fibrous membranes by blending with poly(ester urethane)urea (PEUU) without diselenide bonds. The presence of catalytic sites in the main chain demonstrates stable and long-lasting NO catalytic activity, while the porous structure of the fibrous membranes ensures uniform distribution of the catalytic sites and better contact with the donor-containing solution. PEUU/SePEUU50 in 50/50 mass ratio has a physiologically adapted rate of NO release, with a sustained generation of NO after exposure to PBS at 37 °C for 30 d. PEUU/SePEUU50 has a low hemolysis and protein adsorption, with mechanical properties in the wet state matching those of natural vascular tissues. It can promote the adhesion and proliferation of human umbilical vein endothelial cells in vitro and control the proliferation of vascular smooth muscle cells in the presence of NO generation. This study exhibits the electrospun fibrous membranes have potential for utilizing as hemocompatible biomaterials for regeneration of blood-contacting tissues.

Vinylogous Urea—Urethane Vitrimers: Accelerating and Inhibiting Network Dynamics through Hydrogen Bonding

AbstractVinylogous urethane (VUO) based polymer networks are widely used as catalyst‐free vitrimers that show rapid covalent bond exchange at elevated temperatures. In solution, vinylogous ureas (VUN) undergo much faster bond exchange than VUO and are highly dynamic at room temperature. However, this difference in reactivity is not observed in their respective dynamic polymer networks, as VUO and VUN vitrimers prepared herein with very similar macromolecular architectures show comparable stress relaxation and creep behavior. However, by using mixtures of VUO and VUN linkages within the same network, the dynamic reactions can be accelerated by an order of magnitude. The results can be rationalized by the effect of intermolecular hydrogen bonding, which is absent in VUO vitrimers, but is very pronounced for vinylogous urea moieties. At low concentrations of VUN, these hydrogen bonds act as catalysts for covalent bond exchange, while at high concentration, they provide a pervasive vinylogous urea ‐ urethane (VU) network of strong non‐covalent interactions, giving rise to phase separation and inhibiting polymer chain dynamics. This offers a straightforward design principle for dynamic polymer materials, showing at the same time the possible additive and synergistic effects of supramolecular and dynamic covalent polymer networks.

Nerve Wrap for Local Delivery of FK506/Tacrolimus Accelerates Nerve Regeneration.

Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ ≥ 2.0 ng/mL); whereas the drug concentrations within the ION and muscle were much higher, demonstrating the local delivery of FK506 to treat PNI. An immunohistological assessment of ION showed increased myelin expression for animals assigned to neurorrhaphy with PEUU-FK506 treatment compared to untreated or systemic-FK506-treated animals, suggesting that improved PNI outcomes using PEUU-FK506 is mediated by the modulation of Schwann cell activity.

Nanodiamond reinforced self-healing and transparent poly(urethane–urea) protective coating for scratch resistance

ABSTRACT With increasing demand for scratch-resistant flexible electronics, the development of transparent coatings with good scratch resistance and self-healing properties has emerged as a key research topic. In this study, a high-strength self-healing poly(urethane – urea) (PUU)-based nanocomposite coating was prepared by introducing functionalized nanodiamond (ND) into a PUU matrix via solution blending. The PUU matrix had hard-segment repeating units and was constructed using isophorone diamine and isophorone isocyanate. The ND particles were modified using a silane coupling agent, 3-aminopropyltriethoxysilane, to obtain well-dispersed KH-ND nanoparticles. KH-ND promoted microphase separation in the PU matrix, inducing the formation of dense and homogeneous hard domains that dissipated stress, prevented further crack development, and improved the mechanical properties and scratch resistance of the coating. In addition, the coating exhibited excellent self-healing properties. Fourier-transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were used to characterize the self-healing and hardening mechanisms of the coating. The environmentally friendly PUU/KH-ND coating is easy to prepare and has broad application prospects in transparent and anti-scratch coatings for flexible electronics, automobiles, and home appliances.

Emulsion templating of simultaneously-synthesized interpenetrating polymers with degradable components for hierarchical porosities

Hierarchically porous polymers are of interest for a variety applications including adsorption, catalysis, scaffolds, energy storage, and controlled release. In this work, two simultaneous, mutually exclusive reactions within the external phases of water-in-oil high internal phase emulsions (HIPEs) were used to generate macroporous semi-interpenetrating polymer network (semi-IPN) polyHIPE monoliths. The styrenic copolymer of vinylbenzyl chloride (VBC) and divinylbenzene (DVB) was synthesized using free radical polymerization. The non-crosslinked poly(urethane urea) (PUU), based on a polycaprolactone (PCL) triol, was synthesized using step-growth polymerization. The open-cell, semi-IPN polyHIPEs had densities of ∼0.17 g/cm3, corresponding to porosities of ∼84 %. The semi-IPN polyHIPE with the higher P(VBC-co-DVB) content (75 wt %) exhibited a porous structure typical of polyHIPEs, with an average void diameter of ∼10 μm. The porous structure of the semi-IPN polyHIPE with the lower P(VBC-co-DVB) content (50 wt %) resembled a network of channels. Hierarchical porosities were generated by either etching the flexible PCL-based non-crosslinked PUU to generate mesoporosity or by hypercrosslinking the stiff styrenic copolymer framework to generate microporosity. Etching the semi-IPN polyHIPEs in 3 M NaOH removed most of the PUU. Hypercrosslinking generated microporosity and specific surface areas of 445 and 176 m2/g for 75 and 50 wt % P(VBC-co-DVB), respectively. In the semi-IPNs, the hypercrosslinking process also generated mesoporosity from the removal of some of the PUU.

Poly(Siloxane–Propylene Oxide–Urethane–Ureas) Based on Cycloaliphatic Diisocyanates: Synthesis and Properties

New network poly(siloxane–propylene oxide–urethane–ureas) based on α,ω-bis[(3-aminopropyl)diethoxy]oligodimethylsiloxanes, oligo(propylene oxide), and cycloaliphatic diisocyanates are synthesized. The resulting polymers are studied by differential scanning calorimetry and thermogravimetric analysis; their stress–strain characteristics are elucidated. These polymers are found to feature microphase separation and, consequently, two glass transition temperatures, defined by the chemical structures of the microphases. It is shown that an increase in the molecular weight and mass content of siloxane blocks leads to a decrease in the elastic modulus and tensile strength.

There is no difference in the efficacy of anterior cruciate ligament reconstruction using autograft combined with or without ligament augmentation: a systematic review and meta-analysis.

This study aims to determine the efficacy of anterior cruciate ligament reconstruction (ACLR) using autograft combined with or without ligament augmentation. A computerized search of the databases was conducted, including PubMed, Web of Science, Embase, Scopus and the Cochrane Library. Only prospective or retrospective comparative studies with a minimum 2-year follow-up were considered for inclusion. Two independent reviewers performed data extraction and methodological quality assessment. A Mantel-Haenszel analysis was used for the pooling of results. Sensitivity analysis was performed to maintain the stability of results. The egger test was applied to assess the publication bias. Fourteen studies were included. The total cohort was 1353 patients (non-augmented group: 763 patients; augmented group: 590 patients). There were three Randomized Controlled Trials (RCTs, Level I), six retrospective comparative studies (Level III) and five case-control studies (Level III). The follow-up rate was ≥ 88% and the follow-up periods were ≥ 24months in all included studies. The augmented graft used to compare with autograft included the Ligament Augmentation Device (LAD), the Ligament Advanced Reinforcement System (LARS) artificial ligament, FiberTape, hamstring tendon allograft, degradable poly (urethane urea). No significant differences were observed between the augmented and non-augmented groups regarding postoperative patient-reported outcomes (PROs), including the International Knee Documentation Committee score, Lysholm score and Tegner score, knee laxity, including KT-1000, side-to-side difference, Lachman test and pivot shift and rate of graft failure. ACLR using autografts combined with ligament augmentation shows no advantages in PROs, knee laxity and graft failure rate compared with using autografts only. Level III. The research protocol was registered at the PROSPERO database (CRD42022324784).

Tissue formation and host remodeling of an elastomeric biodegradable scaffold in an ovine pulmonary leaflet replacement model.

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response.

Polyester urethane urea (PEUU) functionalization for enhanced anti-thrombotic performance: advancing regenerative cardiovascular devices through innovative surface modifications.

Introduction: Thrombogenesis, a major cause of implantable cardiovascular device failure, can be addressed through the use of biodegradable polymers modified with anticoagulating moieties. This study introduces a novel polyester urethane urea (PEUU) functionalized with various anti-platelet deposition molecules for enhanced antiplatelet performance in regenerative cardiovascular devices. Methods: PEUU, synthesized from poly-caprolactone, 1,4-diisocyanatobutane, and putrescine, was chemically oxidized to introduce carboxyl groups, creating PEUU-COOH. This polymer was functionalized in situ with polyethyleneimine, 4-arm polyethylene glycol, seleno-L-cystine, heparin sodium, and fondaparinux. Functionalization was confirmed using Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy. Bio-compatibility and hemocompatibility were validated through metabolic activity and hemolysis assays. The anti-thrombotic activity was assessed using platelet aggregation, lactate dehydrogenase activation assays, and scanning electron microscopy surface imaging. The whole-blood clotting time quantification assay was employed to evaluate anticoagulation properties. Results: Results demonstrated high biocompatibility and hemocompatibility, with the most potent anti-thrombotic activity observed on pegylated surfaces. However, seleno-L-cystine and fondaparinux exhibited no anti-platelet activity. Discussion: The findings highlight the importance of balancing various factors and addressing challenges associated with different approaches when developing innovative surface modifications for cardiovascular devices.

Carbon nanotube reinforced biobased poly(urethane urea) covalent adaptable network composite

AbstractA solvent‐free approach was developed to incorporate carbon nanotube (CNT) into castor oil derived poly(urethane urea) (PPU) covalent adaptable network (CAN) based on dynamic piperidine‐urea bonds to fabricate CNT reinforced PPU composites. The approach includes two steps i.e., pre‐polymerization of castor with isophorone diisocyanate in flask and subsequent chain‐extension with 1,3‐bis(4‐piperidinyl)propane (PIP) in the presence of CNT in an internal mixer. The effect on CNT content of the morphology, mechanical property, stress relaxation, and reprocessability of the PPU/CNT composites was investigated in detail. The results demonstrated that CNT dispersed well in the PPU networks due to the applied strong shear force which facilitated the dispersion of CNT in the PPU matrix before cross‐linking. The well‐dispersed CNT reinforced the mechanical properties of PPU significantly and the Young's modulus (E) of the composites were enhanced significantly when the content of CNT was ≥6 wt% due to the formation of CNT network in the PPU matrix. When the content of CNT was 10 wt%, the E of PPU‐10%CNT was 927.59 ± 149.05 MPa, which was improved by ~60% compared to PPU. The reprocessability of the PPU network was remained although the stress relaxation rate was reduced with incorporation and increasing content of CNT. In addition, the PPU/CNT composites could be degraded chemically to recycle CNT through reaction of the dynamic piperidine‐urea bonds with additional PIP.

Creating and Transferring an Innervated, Vascularized Muscle Flap Made from an Elastic, Cellularized Tissue Construct Developed In Situ.

Reanimating facial structures following paralysis and muscle loss is a surgical objective that would benefit from improved options for harvesting appropriately sized muscle flaps. The objective of this study is to apply electrohydrodynamic processing to generate a cellularized, elastic, biocomposite scaffold that could develop and mature as muscle in a prepared donor site in vivo, and then be transferred as a thin muscle flap with a vascular and neural pedicle. First, an effective extracellular matrix (ECM) gel type is selected for the biocomposite scaffold from three types of ECM combined with poly(ester urethane)urea microfibers and evaluated in rat abdominal wall defects. Next, two types of precursor cells (muscle-derived and adipose-derived) are compared in constructs placed in rat hind limb defects for muscle regeneration capacity. Finally, with a construct made from dermal ECM and muscle-derived stem cells, protoflaps are implanted in one hindlimb for development and then microsurgically transferred as a free flap to the contralateral limb where stimulated muscle function is confirmed. This construct generation and in vivo incubation procedure may allow the generation of small-scale muscle flaps appropriate for transfer to the face, offering a new strategy for facial reanimation.

Cardiac valve scaffold design: Implications of material properties and geometric configuration on performance and mechanics

Development of tissue engineered scaffolds for cardiac valve replacement is nearing clinical translation. While much work has been done to characterize mechanical behavior of native and bioprosthetic valves, and incorporate those data into models improving valve design, similar work for degradable valve scaffolds is lacking. This is particularly important given the implications mechanics have on short-term survival and long-term remodeling. As such, this study aimed to characterize spatially-resolved strain profiles on the leaflets of degradable polymeric valve scaffolds, manipulating common design features such as material stiffness by blending poly(carbonate urethane)urea with stiffer polymers, and geometric configuration, modeled after either a clinically-used valve design (Mk1 design) or an anatomically “optimized” design (Mk2 design). It was shown that material stiffness plays a significant role in overall valve performance, with the stiffest valve groups showing asymmetric and incomplete opening during systole. However, the geometric configuration had a significantly greater effect on valve performance as well as strain magnitude and distribution. Major findings in the strain maps included systolic strains having overall higher strain magnitudes than diastole, and peak radial-direction strain concentrations in the base region of Mk1 valves during systole, with a significant mitigation of radial strain in Mk2 valves. The high tunability of tissue engineered scaffolds is a great advantage for valve design, and the results reported here indicate that design parameters have significant and unequal impact on valve performance and mechanics.

BIO26: Engineering Anti-platelet polymers for regenerative cardiovascular applications

Thrombogenesis is the main failure cause of implantable cardiovascular devices. Thrombus formation not only occludes devices but exacerbates immune responses responsible for foreign body reaction. Biodegradable polymers modified with anticoagulating moieties represent a strategy to overcome these limitations. Herein, we propose the use of a novel polyester urethane urea (PEUU) with pendant carboxyl groups for functionalization with different anti-platelet deposition molecules. PEUU was synthesized from PCL (Polycaprolactone), 1,4-diisocyanatobutane and putrescine, and then chemically oxidized to introduce carboxyl groups in the polymer backbone (PEUU-COOH). PEUU-COOH was functionalized in-situ with Polyethyleneimine mW 400 (PEI), 4 arm Polyethylene Glycol (PEG-4-Arm-NH2), seleno-L-cystine, heparin sodium and fondaporinux as anti-platelet deposition molecules. After solvent casting, functionalization was confirmed via Fourier-transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Metabolic activity (MTT) and hemolysis assays were performed to validate biocompatibility. Anti-platelet activity of PRP exposed films was examined via a platelet aggregation assay, through an activation assay via lactate dehydrogenase (LDH), and by surface imaging with scanning electron microscopy (SEM). Whole-blood clotting time quantification assay was carried out to evaluate anticogulating properties. Upon oxidation, PEUU exhibited COOH pendant groups that were successfully employed to conjugate the anti-platelet molecules, obtaining homogeneous films. Overall cytotoxicity was below 20% and the hemolysis was below 5%, suggesting high biocompatibility and hemocompatibility. The most potent anticoagulant activity was obtained for heparin-functionalized materials followed by PEG-4-Arm-NH2 and PEI. Surprisingly, Seleno-L-cystine and Fondaporinux showed no anti-platelet activity. Results indicate that the polymers introduced here are a promising strategy to avoid thrombogenesis in vascular grafts.

Fast (Re)processing of Urea-Containing Polymers Enabled by Dynamic Aminoketoenamide Bonds

This work presents a straightforward strategy to introduce dynamic covalent aminoketoenamide (AKE) onto the backbone of polyurea-based polymers. Bis-vinylogous amides were synthesized from diamines and acetylacetone and used as drop-in agents during the polymerization of compounds featuring amine, hydroxyl, and isocyanate reactive groups. This chemistry leads to AKE-containing poly(urea urethane)s (PUUs) that are thermally healable and reprocessable due to the dissociation of AKE at elevated temperatures. The obtained PUUs displayed faster stress relaxation rates and lower activation energies upon increasing the AKE content, which favored fast processing. Moreover, the ability to act as a hydrogen-bonding acceptor of the two carbonyl groups of the AKE moiety allowed us to toughen the PUUs. Given the facile synthesis of AKE, this method opens a promising route toward recycling and toughening urea-containing polymers on large scales.