A polyurethane-based hydrophilic elastomer with multi-biological functions for small-diameter vascular grafts.

Thrombosis and intimal hyperplasia (IH) are two major problems faced by the small-diameter vascular grafts. Mimicking the native endothelium and physiological elasticity of blood vessels is considered an ideal strategy. Polyurethane (PU) is suitable for vascular grafts in mechanics because of its molecular designability and elasticity; however, it generally lacks the endothelium-like biofunctions and hydrophilicity. To solve this contradiction, a hydrophilic PU elastomer is developed by crosslinking the hydrophobic hard-segment chains containing diselenide with diaminopyrimidine-capped polyethylene glycol (PEG). In this network, the hydrophobic aggregation occurs underwater due to the uninterrupted hard-segment chains, leading to a significant self-enhancement in mechanics, which can be tailored to the elasticity similar to natural vessels by adjusting the crosslinking density. A series of in vitro studies confirm that the hydrophilicity of PEG and biological activities of aminopyrimidine and diselenide give the PU multi-biological functions similar to the native endothelium, including stable catalytic release of nitric oxide (NO) in the physiological level; anti-adhesion and anti-activation of platelets; inhibition of migration, adhesion, and proliferation of smooth muscle cells (SMCs); and antibacterial effect. In vivo studies further prove the good histocompatibility with both significant reduction in immune response and calcium deposition. STATEMENT OF SIGNIFICANCE: Constructing small-diameter vascular grafts similar to the natural vessels is considered an ideal method to solve the restenosis caused by thrombosis and intimal hyperplasia (IH). Because of the long-term stability, bulk modification is more suitable for implanted materials, however, how to achieve the biofunctions, hydrophilicity, and elasticity simultaneously is still a big challenge. In this work, a kind of polyurethane-based elastomer has been designed and prepared by crosslinking the functional long hard-segment chains with PEG soft segments. The underwater elasticity based on hydration-induced stiffening and the multi-biological functions similar to the native endothelium are compatible with natural vessels. Both in vitro and in vivo experiments demonstrate the potential of this PU as small-diameter vascular grafts.

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy.

Currently, the use of piezoelectric materials to provide sustainable and noninvasive bioelectric stimulation to eradicate tumor cells and accelerate wound healing has raised wide attention. The development of a multifunctional piezoelectric elastomer with the ability to perform in situ tumor therapy as well as wound repair is of paramount importance. However, current piezoelectric materials have a large elastic modulus and limited stretchability, making it difficult to match with the dynamic curvature changes of the wound. Therefore, by copolymerizing lactic acid, butanediol, sebacic acid, and itaconic acid to develop a piezoelectric elastomer (PLBSIE), we construct a new ultrasound-activated PLBSIE-based tumor/wound unified therapeutic platform. Excitedly, it showed outstanding piezoelectric performance and high stretchability, and the separated carrier could react with water to generate highly cytotoxic reactive oxygen species (ROS), contributing to effectively killing tumor cells and eliminating bacteria through piezoelectric therapy. In addition, ultrasound-triggered piezoelectric effects could promote the migration and differentiation of wound-healing-related cells, thus accelerating wound healing. Herein, such a piezoelectric elastomer exerted a critical role in postoperative tumor-induced wound therapy and healing with the merits of possessing multifunctional abilities. Taken together, the developed ultrasound-activated PLBSIE will offer a comprehensive treatment for postoperative osteosarcoma therapy.

Sterilization effects on poly(glycerol dodecanedioate): A biodegradable shape memory elastomer for biomedical applications.

Biodegradable shape memory polymers provide unique regenerative medicine approaches in minimally invasive surgeries. Once heated, thermally responsive shape memory polymer devices can be compressed, programmed to fit within a small profile, delivered in the cold programmed state, and expanded when heated to body temperature. We have previously developed a biodegradable shape memory elastomer (SME), poly(glycerol dodecanedioate) (PGD), with transition temperatures near 37°C exhibiting nonlinear elastic properties like numerous soft tissues. Using SMEs in the clinic requires disinfection and sterilization methods that conserve physiochemical, thermomechanical, and shape recovery properties. We evaluated disinfection protocols using 70% ethanol and UV254 nm for research applications and ethylene oxide (EtO) gas sterilization for clinical applications. Samples disinfected with ethanol for 0.5 and 1 min showed no changes in physiochemical material properties, but after 15 min showed slower recovery rates than controls (p < .05). EtO sterilization at 54.4°C decreased transition temperatures and shape recovery rate compared to EtO sterilization at 37.8°C (p < .01) and controls (p < .05). Aging samples for 9 months in a vacuum desiccator significantly reduced shape recovery, and the recovery rate in EtO sterilized samples compared to controls (p < .001). Cytotoxicity testing (ISO-10993.5C:2012) revealed media extractions from EtO sterilized samples, sterilized at 37.8°C, and high-density polyethylene negative control samples exhibit lower cytotoxicity (IC50) than Ethanol 1 min, UV 2 h, and EtO 54.4°C. Cell viability of NIH3T3 fibroblasts on sterilized surfaces was equivalent on EtO 37.7°C, EtO 54.4°C and Ethanol sterilized substrates. Finally, chromogenic bacterial endotoxin testing showed endotoxin levels were below the FDA prescribed levels for devices contacting blood and lymphatic tissues for ethanol 1 min, UV 120 min, EtO 37.7°C, EtO 54.4°C. These findings outline various disinfection and sterilization processes for research and pre-clinical application and provide a pathway for developing custom sterilization cycles for the translation of biomedical devices utilizing PGD shape memory polymers.

3D printing a biocompatible elastomer for modeling muscle regeneration after volumetric muscle loss.

Volumetric muscle loss (VML) injuries due to trauma, tumor ablation, or other degenerative muscle diseases are debilitating and currently have limited options for self-repair. Advancements in 3D printing allow for the rapid fabrication of biocompatible scaffolds with designer patterns. However, the materials chosen are often stiff or brittle, which is not optimal for muscle tissue engineering. This study utilized a photopolymerizable biocompatible elastomer - poly (glycerol sebacate) acrylate (PGSA) - to develop an in vitro model of muscle regeneration and proliferation into an acellular scaffold after VML injury. Mechanical properties of the scaffold were tuned by controlling light intensity during the 3D printing process to match the specific tension of skeletal muscle. The effect of both geometric (channel sizes between 300 and 600 µm) and biologic (decellularized muscle extracellular matrix (dECM)) cues on muscle progenitor cell infiltration, proliferation, organization, and maturation was evaluated in vitro using a near-infrared fluorescent protein (iRFP) transfected cell line to assess cells in the 3D scaffold. Larger channel sizes and dECM coating were found to enhance cell proliferation and maturation, while no discernable effect on cell alignment was observed. In addition, a pilot experiment was carried out to evaluate the regenerative capacity of this scaffold in vivo after a VML injury. Overall, this platform demonstrates a simple model to study muscle progenitor recruitment and differentiation into acellular scaffolds after VML repair.

Biomimetic structure of chitosan reinforced epoxy natural rubber with self-healed, recyclable and antimicrobial ability.

Inspired by biomaterials with hard and soft structures, we reported a type of self-healed, recyclable and antimicrobial elastomers material (ECTS) which exhibited both strong mechanical strength and high toughness. ECTS was designed by furfuryl amine modified epoxy natural rubber (ENR-FA) and furaldehyde modified chitosan (CTS-FUR) through Diels-Alder (D-A) reaction. The dynamic loading capacity of the chitosan skeleton, the stress ductility of the matrix and the dynamic cross-linking between the hard and soft components gave the elastomer excellent mechanical strength, toughness and self-healing ability. The tensile strength and the elongation at break could reach up to 7.55 MPa and 487%, respectively. In addition, due to the reversibility of the covalent bond between chitosan framework and rubber matrix, the crosslinking network destroyed by external force could be reestablished under high temperature stimulation. The mechanical properties of the sample could be restored to more than 90% of the original sample, whether it was complete fracture, cyclic damage or recyclable. ECTS exhibited excellent antibacterial activity against both gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Pseudomonas aeruginosa), with antibacterial efficiency more than 99%. So, ECTS might has a promising application prospect in medical materials, intelligent devices, 4D-printing, etc.

Injectable non-leaching tissue-mimetic bottlebrush elastomers as an advanced platform for reconstructive surgery.

Current materials used in biomedical devices do not match tissue's mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.

Shape-Morphing Fibrous Hydrogel/Elastomer Bilayers Fabricated by a Combination of 3D Printing and Melt Electrowriting for Muscle Tissue Regeneration.

This paper reports an approach for the fabrication of shape-changing bilayered scaffolds, which allow the growth of aligned skeletal muscle cells, using a combination of 3D printing of hyaluronic acid hydrogel, melt electrowriting of thermoplastic polycaprolactone-polyurethane elastomer, and shape transformation. The combination of the selected materials and fabrication methods allows a number of important advantages such as biocompatibility, biodegradability, and suitable mechanical properties (elasticity and softness of the fibers) similar to those of important components of extracellular matrix (ECM), which allow proper cell alignment and shape transformation. Myoblasts demonstrate excellent viability on the surface of the shape-changing bilayer, where they occupy space between fibers and align along them, allowing efficient cell patterning inside folded structures. The bilayer scaffold is able to undergo a controlled shape transformation and form multilayer scroll-like structures with cells encapsulated inside. Overall, the importance of this approach is the fabrication of tubular constructs with a patterned interior that can support the proliferation and alignment of muscle cells for muscle tissue regeneration.

Elastomeric Electrospun Scaffolds of a Biodegradable Aliphatic Copolyester Containing PEG-Like Sequences for Dynamic Culture of Human Endothelial Cells.

In the field of artificial prostheses for damaged vessel replacement, polymeric scaffolds showing the right combination of mechanical performance, biocompatibility, and biodegradability are still demanded. In the present work, poly(butylene-co-triethylene trans-1,4-cyclohexanedicarboxylate), a biodegradable random aliphatic copolyester, has been synthesized and electrospun in form of aligned and random fibers properly designed for vascular applications. The obtained materials were analyzed through tensile and dynamic-mechanical tests, the latter performed under conditions simulating the mechanical contraction of vascular tissue. Furthermore, the in vitro biological characterization, in terms of hemocompatibility and cytocompatibility in static and dynamic conditions, was also carried out. The mechanical properties of the investigated scaffolds fit within the range of physiological properties for medium- and small-caliber blood vessels, and the aligned scaffolds displayed a strain-stiffening behavior typical of the blood vessels. Furthermore, all the produced scaffolds showed constant storage and loss moduli in the investigated timeframe (24 h), demonstrating the stability of the scaffolds under the applied conditions of mechanical deformation. The biological characterization highlighted that the mats showed high hemocompatibility and low probability of thrombus formation; finally, the cytocompatibility tests demonstrated that cyclic stretch of electrospun fibers increased endothelial cell activity and proliferation, in particular on aligned scaffolds.

Strengthened, Antibacterial, and Conductive Flexible Film for Humidity and Strain Sensors.

With the development of artificial intelligence, people are not satisfied with the traditional conductive materials and tend to focus on stretchable and flexible electronic systems. Flexible conductive rubbers have great potential applications in wearable strain sensors. However, the rapid propagation of bacteria during the use of wearable sensors may be an ineluctable threat to humans' health. Herein, a conductive rubber film is fabricated based on carboxylic styrene-butadiene rubber (XSBR), citric acid (CA), and silver nitrate (AgNO3) via a convenient approach, where Ag nanoparticles (Ag NPs) are in situ reduced without sintering at elevated temperatures. The resultant films exhibit many desirable and impressive features, such as strengthened mechanical properties, flexibility, and conductivity. More importantly, the Ag NP flexible conductive films exhibit excellent antibacterial activity against Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria), which have potential applications as flexible antibacterial materials to monitor movements of the human body in real time. Also, because of the hygroscopicity of CA, the resistance of our conductive film is sensitive to various humidities, which can be applied in the humidity sensor.

Effect of sodium benzoate and chlorhexidine gluconate on a bio-thermoplastic elastomer made from thermoplastic starch-chitosan blended with epoxidized natural rubber.

Thermoplastic elastomer (TPE) was developed by blending thermoplastic starch (TPS) with rubber. Thermoplastic starch-chitosan (TPSC) was prepared by the solution mixing of cassava starch, chitosan (CTS) and glycerol in acidified water (lactic acid 1 wt%) at 80 °C follow by melt mixing at 130 °C. Sodium benzoate (BEN) and chlorhexidine gluconate (Cl) were added during the solution mixing as additives for antimicrobial properties. TPSC was melt-mixed with epoxidized natural rubber (ENR) (70/30 wt/wt). The tensile strength and elongation at break of the TPSC/ENR increased with the additive content. Elastic recovery was improved by the addition of Cl. A new peak in the FTIR data confirmed the reaction between the reactive functional groups of the CTS and the additives with the epoxy groups of ENR. These reactions and miscibility of the TPSC/ENR/additives blends improved the mechanical properties, elasticity, morphology, and antimicrobial properties of the blends.

Elastomeric polyurethane porous film functionalized with gastrodin for peripheral nerve regeneration.

The extracellular matrix provides cells with a support structure and an attachment site in actual substrate. Its biochemical and surface properties play an important role in and have significant impact on cell attachment, proliferation, migration, differentiation, and gene expression. Leveraging the hydrophilicity and neuroprotective of gastrodin, a gastrodin/polyurethane (PU) elastomer was developed utilizing in situ polymerization and salt-leaching methods. The results showed that gastrodin/PU film had a good flexibility and supporting strength, as well as hydrophilicity. Thus film possessed highly surface area, interconnected porous structure with a pore size (10~60 µm) for cell attachment, and could provide surface cues to augment neurite extension. For PC12 cells cultured within the films, especially the 5gastrodin/PU group, presented a progressive increase with time, coupled with the upregulation of brain-derived neurotrophic factor and glial cell derived neurotrophic factor expression. This is the first report on the construction of a gastrodin/PU porous film, and the results reveal its promise as a scaffold material for neural tissue engineering.

Suppression of hypersynchronous network activity in cultured cortical neurons using an ultrasoft silicone scaffold.

The spontaneous activity pattern of cortical neurons in dissociated culture is characterized by burst firing that is highly synchronized among a wide population of cells. The degree of synchrony, however, is excessively higher than that in cortical tissues. Here, we employed polydimethylsiloxane (PDMS) elastomers to establish a novel system for culturing neurons on a scaffold with an elastic modulus resembling brain tissue, and investigated the effect of the scaffold's elasticity on network activity patterns in cultured rat cortical neurons. Using whole-cell patch clamp to assess the scaffold effect on the development of synaptic connections, we found that the amplitude of excitatory postsynaptic current, as well as the frequency of spontaneous transmissions, was reduced in neuronal networks grown on an ultrasoft PDMS with an elastic modulus of 0.5 kPa. Furthermore, the ultrasoft scaffold was found to suppress neural correlations in the spontaneous activity of the cultured neuronal network. The dose of GsMTx-4, an antagonist of stretch-activated cation channels (SACs), required to reduce the generation of the events below 1.0 event per min on PDMS substrates was lower than that for neurons on a glass substrate. This suggests that the difference in the baseline level of SAC activation is a molecular mechanism underlying the alteration in neuronal network activity depending on scaffold stiffness. Our results demonstrate the potential application of PDMS with biomimetic elasticity as cell-culture scaffold for bridging the in vivo-in vitro gap in neuronal systems.

Inkjet Printing of Curing Agent on Thin PDMS for Local Tailoring of Mechanical Properties.

Rapid prototyping of thin, stretchable substrates with engineered stiffness gradients at desired locations has potential impact in the robustness of skin-wearable electronics, as the gradients can inhibit cracking of interconnect and delamination of embedded electronic chips. Drop-on-demand inkjetting of thinned polydimethylsiloxane (PDMS) curing agent onto a spin-cast 80 µm-thick 20:1 (base: curing agent) PDMS substrate sets the elastic modulus of the subsequently cured film with sub-millimeter accuracy. The inkjet process creates digitally defined stiffness gradient spans as small as 100 µm for single droplets. Varying the drop density results in differences in elastic modulus of up to 80%. In jetting tests of curing agent into pure base PDMS, a continuous droplet spacing of 100 µm results in smooth lines with total widths of 1 mm and a curing agent gradient span of ≈300 µm. Release of freeform mesh elastomer microstructures by removing the uncured base after selective jetting of curing agent into pure base PDMS results in structural line width resolution down to 500 µm.

Synthesis and characterization of stable and biological active chitin-based polyurethane elastomers.

In this work, the preparation of novel biocompatible polyurethane (PU) elastomers were carried out using curcumin and 1,4-butanediol (1,4-BDO) via step growth polymerization reaction of hydroxyl terminated polybutadiene (HTPB), toluene diisocyanate (TDI) and chitin to improve the biocompatibility, antibacterial and antioxidant properties of PU elastomers. Five samples were synthesized by varying moles ratio of curcumin and 1,4-BDO. The structural study of blends was done by FTIR spectroscopy which confirmed the incorporation of curcumin and 1,4-BDO into the polyurethane matrix. TGA analysis of polyurethane (PU) blends showed good thermal stability with 0.25 M curcumin and 1.75 M 1,4-BDO. Measurements of antibacterial properties were done via agar diffusion method which showed outstanding potential against selected strains of bacteria. The results revealed that biocompatibility, antibacterial and antioxidant potential of purposed polyurethanes elastomers were improved by the incorporation of curcumin which might be the precursor of biomedical applications. Collectively, this work is a footstep towards the synthesis of innovative biocompatible materials which made it suitable for biological applications.

Self-Healing Polyester Urethane Supramolecular Elastomers Reinforced with Cellulose Nanocrystals for Biomedical Applications.

Stretchable self-healing urethane-based biomaterials have always been crucial for biomedical applications; however, the strength is the main constraint of utilization of these healable materials. Here, a series of novel, healable, elastomeric, supramolecular polyester urethane nanocomposites of poly(1,8-octanediol citrate) and hexamethylene diisocyanate reinforced with cellulose nanocrystals (CNCs) are introduced. Nanocomposites with various amounts of CNCs from 10 to 50 wt% are prepared using solvent casting technique followed by the evaluation of their microstructural features, mechanical properties, healability, and biocompatibility. The synthesized nanocomposites indicate significantly higher tensile modulus (approximately 36-500-fold) in comparison to the supramolecular polymer alone. Upon exposure to heat, the materials can reheal, but nevertheless when the amount of CNC is greater than 10 wt%, the self-healing ability of nanocomposites is deteriorated. These materials are capable of rebonding ruptured parts and fully restoring their mechanical properties. In vitro cytotoxicity test of the nanocomposites using human dermal fibroblasts confirms their good cytocompatibility. The optimized structure, self-healing attributes, and noncytotoxicity make these nanocomposites highly promising for tissue engineering and other biomedical applications.

Mimicking "J-Shaped" and Anisotropic Stress-Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites.

An ex vivo heart perfusion device preserves the donor heart in a warm beating state during transfer between extraction and implantation surgeries. One of the current challenges includes the use of rigid and noncompliant plastic tubes, which causes injuries to the heart at the junction between the tissue and the tube. The compliant and rapidly strain-stiffening mechanical property that generates a "J-shaped" stress-strain behavior is necessary for producing the Windkessel effect, which ensures continuous flow of blood through the aorta. In this study, we mimic the J-shaped and anisotropic stress-strain behavior of human aorta in synthetic elastomers to replace the problematic noncompliant plastic tube. First, we assess the mechanical properties of human (n = 1) and porcine aorta (n = 14) to quantify the nonlinear and anisotropic behavior under uniaxial tensile stress from five different regions of the aorta. Second, fabric-reinforced elastomer composites were prepared by reinforcing silicone elastomers with embedded fabrics in a trilayer geometry. The knitted structures of the fabric provide strain-stiffening as well as anisotropic mechanical properties of the resulting composite in a deterministic manner. By optimizing the combination between different elastomers and fabrics, the resulting composites matched the J-shaped and anisotropic stress-strain behavior of natural human and porcine aorta. Finally, improved analytical constitutive models based on Gent's and Mooney-Rivlin's constitutive model (to describe the elastomer matrix) combined with Holzapfel-Gasser-Ogden's model (to represent the stiffer fabrics) were developed to describe the J-shaped behavior of the natural aortas and the fabric-reinforced composites. We anticipate that the suggested fabric-reinforced silicone elastomer composite design concept can be used to develop complex soft biomaterials, as well as in emerging engineering fields such as soft robotics and microfluidics, where the Windkessel effect can be useful in regulating the flow of fluids.

Quasi-3D morphology and modulation of focal adhesions of human adult stem cells through combinatorial concave elastomeric surfaces with varied stiffness.

In vivo cell niches are complex architectures that provide a wide range of biochemical and mechanical stimuli to control cell behavior and fate. With the aim to provide in vitro microenvironments mimicking physiological niches, microstructured substrates have been exploited to support cell adhesion and to control cell shape as well as three dimensional morphology. At variance with previous methods, we propose a simple and rapid protein subtractive soft lithographic method to obtain microstructured polydimethylsiloxane substrates for studying stem cell adhesion and growth. The shape of adult renal stem cells and nuclei is found to depend predominantly on micropatterning of elastomeric surfaces and only weakly on the substrate mechanical properties. Differently, focal adhesions in their shape and density but not in their alignment mainly depend on the elastomer stiffness almost regardless of microscale topography. Local surface topography with concave microgeometry enhancing adhesion drives stem cells in a quasi-three dimensional configuration where stiffness might significantly steer mechanosensing as highlighted by focal adhesion properties.

Fabrication of elastomer pillar arrays with elasticity gradient for cell migration, elongation and patterning.

The elasticity of the cell and that of the supporting extracellular matrices (ECMs) in tissue are correlated. In some cases, the modulus of the ECM varies with a high spatial gradient. To study the effect of such a modulus gradient on the cell culture behavior, we proposed a novel yet straightforward method to fabricate elastomeric micropillar substrates with different height gradients, which could provide a large range of elasticity gradient from 2.4 kPa to 60 kPa. The micropillars were integrated into a microfluidic chip to demonstrate the elasticity variation, with the theoretical results proving that the elasticity of the two micropillar substrates was in the same range but with distinguished gradient strengths. Fibroblast seeded on the micropillar substrates showed migration toward the stiffer area but their elongation highly depended on the strength of the elasticity gradient. In the case of high gradient strength, cells could easily migrate to the stiffer area and then elongated perpendicularly to their migration direction. Otherwise, cells were mostly elongated in the direction of the gradient. Our results also showed that when the cell density was sufficiently high, cells tended to be oriented in the same direction locally, which was affected by both underneath pillars and cell-cell contact. The elasticity gradients could also be generated in a ripple shape, and the cell behavior showed the feasibility of using the micropillars for cell patterning applications. Moreover, the gradient pillar substrates were further used for the aggregate formation of induced pluripotent stem cells, thus providing an alternative substrate to study the effect of substrate elasticity on stem cell behavior and differentiation.

Fast degrading elastomer stented fascia remodels into tough and vascularized construct for tracheal regeneration.

Tracheal reconstruction remains a major surgical challenge, mainly owing to the scarce of resilient hollow grafts with identifiable vascular pedicle in humans. In this study, we developed a three-layer, elastomeric, trachea-like composite made of poly glycerol sebacate (PGS) and polycaprolactone (PCL), which presented appropriate resilient property, timely degradation and interconnected pores. C shape PCL rings fabricated with selective laser sintering (SLS) techniques are regularly positioned around porous PGS tubes and fixed by PCL electrospinning sheath. Such an elastomeric composite underwent host remodeling including rapid vascularization and tissue infiltration after fascia wrapping. With degrading of PGS, C rings well incorporated into growing fascia and lead to the formation of pedicled tracheal grafts, which attributes to the strong and resilient properties of generated hollow grafts thus enabled orthotopic transplantation in segmental tracheal defect. Progressive remodeling on such vascularized and mechanically stable grafts resulted in epithelium regeneration on luminal side as well as production of adequate amount of collagen and elastin, which warrantees the air passage during breathing. Future study employing large animal models more representative of human tracheal regeneration is warranted before clinical translation. Using fast degrading PGS combined with PCL rings represents a philosophical shift from the prevailing focus on tough grafts in airway reconstruction and may impact regenerative medicine in general.

Development of metformin chain extended polyurethane elastomers as bone regenerative films.

In this study, novel elastomeric biodegradable bone regenerative films were developed from metformin (Met) and polyurethane (PU). Metformin was selected due to its osteogenic properties and proper chemical structure to react with PU prepolymer. Metformin was integrated into PU macromolecular structure as chain extender after the synthesis of PU prepolymer via condensation polymerization of polycaprolactone diol and hexamethylene diisocyanate. Chemical, thermal, viscoelastic properties of PU-Met films where characterized and discussed in terms of structure-property relationships. PU-Met films had Tg value around -45 °C and showed superior viscoelastic properties under 1 Hz and 10 Hz tensile oscillation frequencies during dynamic mechanical analysis. On the 21st day of biodegradation studies, PU-Met films degraded 2.3 ±â€¯0.1% and 37.8 ±â€¯4.2% in oxidative and enzymatic media, respectively. Cell-material interactions of elastomeric films were investigated by proliferation (MTT assay), alkaline phosphatase activity (ALP), calcium depositions (Alizarin Red Quantification) and morphological evaluations (SEM). Presence of metformin in PU formulation increased MC3T3-E1 attachment, proliferation and calcium deposition.