Choline Chloride-urea Deep Eutectic Mixture Water for the Synthesis of an Amphiphilic Compound of Glyceryl Monocaffeate.

The Lipase-catalyzed synthesis of glyceryl monocaffeate (GMC) in choline chloride-urea of natural deep eutectic solvent (NADES) media is reported to provide amphiphilic character to caffeic acid (CA). The modification of CA into GMC could potentially increase its solubility and widen the application of CA's biological activities in water and oil-based systems. The high conversion was achieved when the reaction was carried out with the addition of more than 20 %v/v water, at a high molar ratio of glycerol and 40°C. It was found that the lipase-catalyzed transesterification of ethyl caffeate (EC) and glycerol in choline chloride-urea of DES media obeyed ping-pong bi-bi mechanism with Vmax = 10.9 mmol.min-1, KmEC = 126.5 mmol and KmGly = 1842.7 mmol.

Modular Synthesis of a Versatile Double-Allylation Reagent for Complex Diol Synthesis.

Double-allylation reagents allow for the construction of highly complex molecules in an expedient fashion. We have developed an efficient, modular, and enantioselective approach towards accessing novel variants of these reagents through Cu/Pd-catalyzed alkenylboration of alkenylboron derivatives. Importantly, we demonstrate novel use of an allylBdan reagent directly in a stereocontrolled allylation without initial deprotection to the boronic ester. These allylation products are employed in a second intermolecular allylation to access complex diol motifs, which has yet to be shown with these types of double-allylation reagents. Overall, the modularity of this approach and the ease in which complex structural motifs can be accessed in a rapid manner signify the importance and utility of this method.

PGMD/curcumin nanoparticles for the treatment of breast cancer.

The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was - 18.9 and - 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75-81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 µM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 µM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.

Synthesis and characterization of novel organo-hydrogel based agar, glycerol and peppermint oil as a natural drug carrier/release material.

The very recent Covid-19 pandemic has made the need to understand biocompatible polymers as support material in drug delivery systems and controlled release clearer, especially for organo-hydrogels. This study aims to synthesize various new polymeric materials called gels, hydrogels, and organo-hydrogels according to the monomer used and to investigate their use as drug release systems. The agar-glycerol (AG) pair was used to synthesize the polymers, N, N, methylene bisacrylamide (MBA, m) and glutaraldehyde (GA, g) were used as cross-linkers and peppermint oil (PmO) was included to obtain the organo-hydrogels. Therefore, one AG gel and two p (AG-m) and p (GA-g) hydrogels were synthesized within the scope of the study. Six different organo-hydrogels based on p(AG-m-PmO) or p (AG-g-PmO) were also synthesized by varying the amount of peppermint oil. Paracetamol and carboplatin were selected as the sample drugs. Synthesized gels, hydrogels and organo-hydrogels were characterized by FTIR and SEM analysis. Additionally, swelling behaviors of the synthesized gels were investigated in different media (ID water, tap water, ethanol, acetone, ethanol/ID water (1:1), acetone/ID water (1:1) and gasoline) and at different pHs. Moreover, it was determined that organo-hydrogels were blood compatible and had antioxidant properties based on hemolysis, blood clotting and antioxidant analysis. Therefore, the release of paracetamol (a known antipyretic-painkiller, recommended and used in the treatment of Covid-19) and carboplatin (widely used in cancer treatment) were studied. Evidently, as the amount of PMO oil increases, the -OH groups in organo-hydrogels will increase and the chemical and physical bonding rates will increase; therefore it was observed that increasing peppermint oil in the organo-hydrogels structure to 0.3 mL stimulated the release of the drugs. For instance, maximum paracetamol release amount from p(AG-g-PmO) and p(AG-m-PmO) organo-hydrogels was calculated to be 72.3% at pH 7.4 and 69.8% at pH 2.0, respectively. The maximum carboplatin release amount from p(AG-g-PmO) and p(AG-m-PmO) organo-hydrogels was calculated to be 99.7% at pH 7.4 and 100% at pH 7.4, respectively. It was concluded that the synthesized organo-hydrogels might easily be used as drug carrier and controlled drug release materials.

Mucin-Inspired, High Molecular Weight Virus Binding Inhibitors Show Biphasic Binding Behavior to Influenza A Viruses.

Multivalent binding inhibitors are a promising new class of antivirals that prevent virus infections by inhibiting virus binding to cell membranes. The design of these inhibitors is challenging as many properties, for example, inhibitor size and functionalization with virus attachment factors, strongly influence the inhibition efficiency. Here, virus binding inhibitors are synthesized, the size and functionalization of which are inspired by mucins, which are naturally occurring glycosylated proteins with high molecular weight (MDa range) and interact efficiently with various viruses. Hyperbranched polyglycerols (hPGs) with molecular weights ranging between 10 and 2600 kDa are synthesized, thereby hitting the size of mucins and allowing for determining the impact of inhibitor size on the inhibition efficiency. The hPGs are functionalized with sialic acids and sulfates, as suggested from the structure of mucins, and their inhibition efficiency is determined by probing the inhibition of influenza A virus (IAV) binding to membranes using various methods. The largest, mucin-sized inhibitor shows potent inhibition at pm concentrations, while the inhibition efficiency decreases with decreasing the molecular weight. Interestingly, the concentration-dependent IAV inhibition shows a biphasic behavior, which is attributed to differences in the binding affinity of the inhibitors to the two IAV envelope proteins, neuraminidase, and hemagglutinin.

Immobilization of Lecitase® Ultra onto the Amino-functionalized SBA-15 and their Applications in Glycerolysis.

In this study, Lecitase® Ultra (LU) was immobilized onto the parent and the amino-functionalized SBA-15. The immobilization conditions were studied and the activity of the parent SBA-15 supported LU (SBA-15-LU) was found to be at 2177.78 ± 101.84 U/g. After 3-aminopropyl and n-(2-aminoethyl)-3-aminopropyl groups functionalization, enzymatic activity was increased to 3555.56 ± 200.21 and 3444.44 ± 346.41 U/g respectively. The immobilized LU samples were then used to catalyze glycerolysis. The possibility for diacylglycerols (DAG) and monoacylglycerols (MAG) production was evaluated and it was found only suitable for DAG production. In addition, the glycerolysis activity of the immobilized LU was impaired by the tert-pentanol and solvent-free was found suitable. Similar DAG content over 50 wt% could be obtained from glycerolysis by the three immobilized LU samples. The reusability in glycerolysis was evaluated, and 9.79 % of the initial glycerolysis activity was remained from the SBA-15-LU after 5 cycles of reuse. Encouragingly, after 3-aminopropyl and n-(2-aminoethyl)-3-aminopropyl groups functionalization, 62.93 and 83.91% of their initial activity was respectively remained after 5 cycles of reuse.

Environmentally Friendly and Biodegradable Ultrasensitive Piezoresistive Sensors for Wearable Electronics Applications.

Highly sensitive, flexible sensors that can be manufactured with minimum environmental footprint and be seamlessly integrated into wearable devices are required for real-time tracking of complex human movement, gestures, and health conditions. This study reports on how biodegradation can be used to enhance the sensitivity and electromechanical performance of piezoresistive sensors. Poly(glycerol sebacate) (PGS) elastomeric porous sensor was synthesized and blended with multiwall carbon nanotubes (MWCNTs) and sodium chloride (NaCl). Because of their unique porous characteristics, a single linear behavior over a large range of pressures (≤8 kPa) and an increase in their sensitivity from 0.12 ± 0.03 kPa-1 up to 8.00 ± 0.20 kPa-1 was achieved after 8 weeks in a simulated body fluid media. They can detect very low pressures (100 Pa), with negligible hysteresis, reliability, long lifetime (>200 000 cycles), short response time (≤20 ms), and high force sensitivity (≤4 mN). The characteristics of the developed foam sensors match the sensing characteristics of the human finger to pave the way toward low-footprint wearable devices for applications including human movement and condition monitoring, recreation, health and wellness, virtual reality, and tissue engineering.

Control the Mechanical Properties and Degradation of Poly(Glycerol Sebacate) by Substitution of the Hydroxyl Groups with Palmitates.

Mechanical properties and degradation profile are important parameters for the applications of biodegradable polyester such as poly(glycerol sebacate) in biomedical engineering. Here, a strategy is reported to make palmitate functionalized poly(glycerol sebacate) (PPGS) to alter the polymer hydrophobicity, crystallinity, microstructures and thermal properties. The changes of these intrinsic properties impart tunable degradation profiles and mechanical properties to the resultant elastomers depending on the palmitate contents. When the palmitates reach up to 16 mol%, the elastic modulus is tuned from initially 838 ± 55 kPa for the PGS to 333 ± 21 kPa for the PPGS under the same crosslinking conditions. The elastomer undergoes reversible elastic deformations for at least 1000 cycles within 20% strain without failure and shows enhanced elasticity. The polymer degradation is simultaneously inhibited because of the increased hydrophobicity. This strategy is different with other PGS modifications which could form a softer elastomer with less crosslinks but typically lead to a quicker degradation. Because the materials are made from endogenous molecules, they possess good cytocompatibility similar to the PGS control. Although these materials are designed specifically for small arteries, it is expected that they will be useful for other soft tissues too.

Polyglycerol Hyperbranched Polyesters: Synthesis, Properties and Pharmaceutical and Biomedical Applications.

In a century when environmental pollution is a major issue, polymers issued from bio-based monomers have gained important interest, as they are expected to be environment-friendly, and biocompatible, with non-toxic degradation products. In parallel, hyperbranched polymers have emerged as an easily accessible alternative to dendrimers with numerous potential applications. Glycerol (Gly) is a natural, low-cost, trifunctional monomer, with a production expected to grow significantly, and thus an excellent candidate for the synthesis of hyperbranched polyesters for pharmaceutical and biomedical applications. In the present article, we review the synthesis, properties, and applications of glycerol polyesters of aliphatic dicarboxylic acids (from succinic to sebacic acids) as well as the copolymers of glycerol or hyperbranched polyglycerol with poly(lactic acid) and poly(ε-caprolactone). Emphasis was given to summarize the synthetic procedures (monomer molar ratio, used catalysts, temperatures, etc.,) and their effect on the molecular weight, solubility, and thermal and mechanical properties of the prepared hyperbranched polymers. Their applications in pharmaceutical technology as drug carries and in biomedical applications focusing on regenerative medicine are highlighted.

Dendritic Polyglycerol-Derived Nano-Architectures as Delivery Platforms of Gemcitabine for Pancreatic Cancer.

Dendritic polyglycerol-co-polycaprolactone (PG-co-PCL)-derived block copolymers are synthesized and explored as nanoscale drug delivery platforms for a chemotherapeutic agent, gemcitabine (GEM), which is the cornerstone of therapy for pancreatic ductal adenocarcinoma (PDAC). Current treatment strategies with GEM result in suboptimal therapeutic outcome owing to microenvironmental resistance and rapid metabolic degradation of GEM. To address these challenges, physicochemical and cell-biological properties of both covalently conjugated and non-covalently stabilized variants of GEM-containing PG-co-PCL architectures have been evaluated. Self-assembly behavior, drug loading and release capacity, cytotoxicity, and cellular uptake properties of these constructs in monolayer and in spheroid cultures of PDAC cells are investigated. To realize the covalently conjugated carrier systems, GEM, in conjunction with a tertiary amine, is attached to the polycarbonate block grafted from the PG-co-PCL core. It is observed that pH-dependent ionization properties of these amine side-chains direct the formation of self-assembly of block copolymers in the form of nanoparticles. For non-covalent encapsulation, a facile "solvent-shifting" technique is adopted. Fabrication techniques are found to control colloidal and cellular properties of GEM-loaded nanoconstructs. The feasibility and potential of these newly developed architectures for designing carrier systems for GEM to achieve augmented prognosis for pancreatic cancer are reported.

One-Pot Synthesis of Poly(glycerol- co-succinic acid) Nanogels for Dermal Delivery.

Polyglycerol nanogels are three-dimensional polymeric networks with a few hundred nanometer sizes and the ability to encapsulate and deliver cargos for a wide range of biomedical applications. However, time-consuming and multistep synthetic routes as well as milligram-scale production have hindered further development of these nanomaterials. In this work, we report on a straightforward synthetic method for the production of polyglycerol nanoarchitectures. Enzymatic ring-opening copolymerization of a mixture of glycidol and succinic anhydride resulted in polyglycerol nanogels with succinic acid segments in their backbone. Novozyme 435 was used as a dual catalytic agent to support ring-opening polymerization of the above-mentioned cyclic monomers as well as esterification of the produced oligomers to obtain nanogels. While succinic acid segments improved the biodegradability and loading capacity of nanogels, polyglycerol caused water solubility, high functionality, and biocompatibility. Nanogels were loaded with tacrolimus and photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP)-a close congener of the approved photosensitizer temoporfin (mTHPC)-and their ability to improve the skin penetration of these therapeutic agents was investigated. mTHPP delivery experiments on human skin, which were quantified by fluorescence microscopy, showed that these nanogels deposit in the stratum corneum and release the loaded drug to viable epidermis of skin efficiently in comparison with commercially available base cream. Taking advantage of the straightforward synthesis as well as biodegradability, biocompatibility, high loading capacity, and efficient skin penetration, the synthesized nanogels could be used as future topical delivery systems.

Luminescent κ-Carrageenan-Based Electrolytes Containing Neodymium Triflate.

In recent years, the synthesis of polymer electrolyte systems derived from biopolymers for the development of sustainable green electrochemical devices has attracted great attention. Here electrolytes based on the red seaweeds-derived polysaccharide κ-carrageenan (κ-Cg) doped with neodymium triflate (NdTrif3) and glycerol (Gly) were obtained by means of a simple, clean, fast, and low-cost procedure. The aim was to produce near-infrared (NIR)-emitting materials with improved thermal and mechanical properties, and enhanced ionic conductivity. Cg has a particular interest, due to the fact that it is a renewable, cost-effective natural polymer and has the ability of gelling in the presence of certain alkali- and alkaline-earth metal cations, being good candidates as host matrices for accommodating guest cations. The as-synthesised κ-Cg-based membranes are semi-crystalline, reveal essentially a homogeneous texture, and exhibit ionic conductivity values 1⁻2 orders of magnitude higher than those of the κ-Cg matrix. A maximum ionic conductivity was achieved for 50 wt.% Gly/κ-Cg and 20 wt.% NdTrif3/κ-Cg (1.03 × 10-4, 3.03 × 10-4, and 1.69 × 10-4 S cm-1 at 30, 60, and 97 °C, respectively). The NdTrif-based κ-Cg membranes are multi-wavelength emitters from the ultraviolet (UV)/visible to the NIR regions, due to the κ-Cg intrinsic emission and to Nd3+, 4F3/2→4I11/2-9/2.

Synthesis and Pharmacological Evaluation of Novel Selenoethers Glycerol Derivatives for the Treatment of Pain and Inflammation: Involvement of Nitrergic and Glutamatergic Systems.

In the present study, the synthesis of new selenoethers from nucleophilic substitution reaction between organyl halides and nucleophilic species of selenium generated in situ was demonstrated. After, this method was applied for the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the antinociceptive and anti-inflammatory effects, as well as, acute toxicity were evaluated. In the formalin test, the compound 9b caused a reduction in licking time in both phases. Compounds 9b and 9c increased the latency to response in the hot-plate test and reduced the licking time induced by glutamate. Our results revealed the involvement of the nitrergic and/or glutamatergic pathways in the antinociceptive action of the compounds. Additionally, 9b and 9c did not cause any toxicity signals and oxidative stress parameters were not modified by treatments. Here, it was developed an alternative and efficient method for the synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that this class is indeed interesting for the research of new drugs. Graphical Abstract ᅟ.

Molecularly engineered metal-based bioactive soft materials - Neuroactive magnesium ion/polymer hybrids.

The development of bioactive soft materials that can guide cell behavior and have biomimetic mechanical properties is an active and challenging topic in regenerative medicine. A common strategy to create a bioactive soft material is the integration of biomacromolecules with polymers. However, limited by their complex structures and sensitivity to temperature and chemicals, it is relatively difficult to maintain the bioactivity of biomacromolecules during their preparation, storage, and application. Here, a new kind of bioactive soft material based on the molecular integration of metal ions and polymers is designed and exemplified by a hybrid of magnesium ion (Mg2+) and poly(glycerol-sebacate-maleate) (PGSM-Mg). Mg2+ was firmly incorporated into PGSM molecules through a complexation interaction as evidenced by X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR). The PGSM matrix provided the soft nature and facile processing of the hybrid, which could serve as an injectable material and be fabricated into elastic porous three-dimensional (3D) scaffolds. The Mg2+ immobilized in the PGSM chain conferred neuroactivity to the resultant hybrid. PGSM-Mg exhibited adequate biodegradability and a sustained release of Mg2+. PGSM-Mg 3D scaffolds promoted the adhesion and proliferation of Schwann cells (SCs) more effectively than poly(lactic-co-glycolic acid) (PLGA) scaffolds. Furthermore, SCs on PGSM-Mg scaffolds expressed significantly more neural specific genes than those on PLGA, PGS, and PGSM, including nerve growth factor (NGF) and neurotrophic factor-3 (NTF3). All these results indicated that Mg2+ immobilized through molecular integration could efficiently regulate the bioactivity of polymers. In view of the wide availability, diverse bioactivity, and high stability of metal ions, the strategy of molecular coupling of metal ions and polymers is expected to be a new general approach to construct bioactive soft materials. STATEMENT OF SIGNIFICANCE: Bioactive soft materials are designed on the basis of the molecular integration of metal ions and polymers. Immobilized metal ions offer a new way to endow bioactivity to polymers. Different from biomolecules such as proteins and genes, metal ions are quite stable and can resist harsh processing conditions. Further, the polymeric matrix provides the soft nature and facile processing of the hybrid. Different from stiff metal-containing inorganic materials, the hybrid is a biomimetic soft material and can be readily processed just like its polymer precursor under mild conditions. In view of the diversity of metal ions and polymers, this strategy is expected to be a new powerful and general approach to construct bioactive soft materials for a wide range of biomedical applications.

Optimization of the Synthesis of Glycerol Derived Monoethers from Glycidol by Means of Heterogeneous Acid Catalysis.

We present an efficient and green methodology for the synthesis of glycerol monoethers, starting from glycidol and different alcohols, by means of heterogeneous acid catalysis. A scope of Brønsted and Lewis acid catalysts were applied to the benchmark reaction of glycidol and methanol. The selected catalysts were cationic exchangers, such as Nafion NR50, Dowex 50WX2, Amberlyst 15 and K10-Montmorillonite, both in their protonic form and exchanged with Al(III), Zn(II) and Fe(III). Thus, total conversions were reached in short times by using 1 and 5% mol catalyst loading and room temperature, without the need for excess glycidol or the presence of a solvent. Finally, these conditions and the best catalysts were successfully applied to the reaction of glycidol with several alcohols such as butanol or isopropanol.

Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine- graft-ß-cyclodextrin and Hyperbranched Polyglycerol Derivative.

Introducing genes into drug-delivery system for a combined therapy has become a promising strategy for cancer treatment. However, improving the in vivo therapy effect resulted from the high delivery efficiency, low toxicity, and good stability in the blood remains a challenge. For this purpose, the supramolecular inclusion was considered to construct a high-efficiency drug and gene co-delivery system in this work. The oligoethylenimine-conjugated ß-cyclodextrin (ß-CD-PEI600) and benzimidazole-modified four-arm-polycaprolactone-initiated hyperbranched polyglycerol (PCL-HPG-BM) were synthesized as the host and guest molecules, respectively, and then the co-delivery carrier of PCL-HPG-PEI600 was formed from the pH-mediated inclusion interaction between ß-CD and BM. PCL-HPG-PEI600 showed the improved drug (doxorubicin, DOX) and gene (MMP-9 shRNA plasmid, pMMP-9) delivery ability in vivo, and their cellular uptake and intracellular delivery were investigated. Particularly, PCL-HPG-PEI600 showed excellent pMMP-9 delivery ability with significantly higher transfection efficiency than PEI25k due to its excellent serum resistance. For the combined therapy to breast cancer MCF-7 tumor, the co-delivery system of PCL-HPG-PEI600/DOX/pMMP-9 resulted in a much better inhibition effect on MCF-7 cell proliferation and migration in vitro as well as the suppression effect on MCF-7 tumors in vivo compared to those of single DOX or pMMP-9 formulation used. Moreover, PCL-HPG-PEI600 displayed nontoxicity and excellent blood compatibility, suggesting a promising drug and gene co-delivery carrier in combined therapy to tumors.

Dynamic Protein Adsorption onto Dendritic Polyglycerol Sulfate Self-Assembled Monolayers.

Biomaterial surfaces that are in contact with blood are often prone to unspecific protein adsorption and the activation of the blood clotting cascade. Hence, such materials usually must be functionalized with low-fouling or anticoagulant polymer coatings to increase their performance and durability with respect to various applications, for example as implants or in biomedical devices. Many coatings are based on anionic polymers, such as heparin, and are known to have pronounced anticoagulant effects. To assess the ability of a surface to prevent biofouling and to get further insight into its underlying mechanism, studies of the protein adsorption on self-assembled monolayers (SAMs) are often used as a predictive tool. In this article, we synthesized thioctic acid-functionalized dendritic polyglycerol sulfate (dPGS), which is a well-known synthetic heparin mimetic, and immobilized it onto gold model surfaces. The anionic dPGS SAMs were characterized via contact angle measurements and ellipsometry and compared to their neutral dendritic polyglycerol (dPG) counterparts with respect to their single protein adsorption of the two most abundant blood proteins albumin (Alb) and fibrinogen (Fib). In addition, we used QCM-D and ToF-SIMS as complementary techniques to investigate the dynamic, mixed, and sequential adsorption of Alb and Fib. Our results clearly demonstrate an incomplete Vroman effect and indicate the rearrangement of the adsorbed protein layers, which is presumably drive by ionic interactions between the two proteins and the anionic dPGS surface.

Self-assembled, ellipsoidal polymeric nanoparticles for intracellular delivery of therapeutics.

Nanoparticle shape has emerged as a key regulator of nanoparticle transport across physiological barriers, intracellular uptake, and biodistribution. We report a facile approach to synthesize ellipsoidal nanoparticles through self-assembly of poly(glycerol sebacate)-co-poly(ethylene glycol) (PGS-co-PEG). The PGS-PEG nanoparticle system is highly tunable, and the semiaxis length of the nanoparticles can be modulated by changing PGS-PEG molar ratio and incorporating therapeutics. As both PGS and PEG are highly biocompatible, the PGS-co-PEG nanoparticles show high hemo-, immuno-, and cytocompatibility. Our data suggest that PGS-co-PEG nanoparticles have the potential for use in a wide range of biomedical applications including regenerative medicine, stem cell engineering, immune modulation, and cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2048-2058, 2018.

Urethane-based low-temperature curing, highly-customized and multifunctional poly(glycerol sebacate)-co-poly(ethylene glycol) copolymers.

Poly (glycerol sebacate) (PGS), a tough elastomer, has been widely explored in tissue engineering due to the desirable mechanical properties and biocompatibility. However, the complex curing procedure (high temperature and vacuum) and limited hydrophilicity (∼90° of wetting angle) greatly impede its functionalities. To address these challenges, a urethane-based low-temperature setting, PEGylated PGS bioelastomer was developed with and without solvent. By simultaneously tailoring PEG and hexamethylene diisocyanate (HDI) contents, the elastomers X-P-mUs (X referred to the PEG content and m referred to HDI content) with a broad ranging mechanical properties and customized hydrophilicity were constructed. The X-P-mUs synthesized exhibited adjustable tensile Young's modulus, ultimate tensile strength and elongation at break in the range of 1.0 MPa-14.2 MPa, 0.3 MPa-7.6 MPa and 53.6%-272.8%, with the water contact angle varying from 28.6° to 71.5°, respectively. Accordingly, these elastomers showed favorable biocompatibility in vitro and mild host response in vivo. Furthermore, the potential applications of X-P-mU elastomers prepared with solvent-base and solvent-free techniques in biomedical fields were investigated. The results showed that these X-P-mU elastomers with high molding capacity at mild temperature could be easily fabricated into various shapes, used as reinforcement for fragile materials, and controllable delivery of drugs and proteins with excellent bioactivity, demonstrating that the X-P-mU elastomers could be tailored as potential building blocks for diverse applications in biomedical research. STATEMENT OF SIGNIFICANCE: Poly(glycerol sebacate) (PGS), a tough biodegradable elastomer, has received great attentions in biomedical field. But the complex curing procedure and limited hydrophilicity greatly hamper its functionality. Herein, a urethane-based low-temperature setting, PEGylated PGS (PEGS-U) bioelastomer with highly-customized mechanical properties, hydrophilicity and biodegradability was first explored. The synthesized PEGS-U showed favorable biocompatibility both in vitro and in vivo. Furthermore, the PEGS-U elastomer could be easily fabricated into various shapes, used as reinforcement for fragile materials, and controllable delivery of drugs and proteins with excellent bioactivity. This versatile, user-tunable bioelastomers should be a promising biomaterials for biomedical applications.

Development of various composition multicomponent chitosan/fish collagen/glycerin 3D porous scaffolds: Effect on morphology, mechanical strength, biostability and cytocompatibility.

The various composition multicomponent chitosan/fish collagen/glycerin 3D porous scaffolds were developed and investigated the effect of various composition chitosan/fish collagen/glycerin on scaffolds morphology, mechanical strength, biostability and cytocompatibility. The scaffolds were fabricated via freeze-drying technique. The effects of various compositions consisting in 3D scaffolds were investigated via FT-IR analysis, porosity, swelling and mechanical tests, and effect on the morphology of scaffolds investigated microscopically. The biostability and cytocompatibility tests were used to explore the ability of scaffolds to use for tissue engineering application. The average pore sizes of scaffolds were in range of 100.73±27.62-116.01±52.06, porosity 71.72±3.46-91.17±2.42%, tensile modulus in dry environment 1.47±0.08-0.17±0.03MPa, tensile modulus in wet environment 0.32±0.03-0.14±0.04MPa and biodegradation rate (at day 30) 60.38±0.70-83.48±0.28%. In vitro culture of human fibroblasts and keratinocytes showed that the various composition multicomponent 3D scaffolds were good cytocompatibility however, the scaffolds contained high amount of fish collagen excellently facilitated cell proliferation and adhesion. It was found that the high amount fish collagen and glycerin scaffolds have high porosity, enough mechanical strength and biostability, and excellent cytocompatibility.