Ethyl Ester Diisocyanate Research Articles

Polymerization-induced emission and selective detection to Fe3+/ Fe2+ of triazine-containing polyureas

In this study, four polyureas with triazine moiety (PUAs) were successfully synthesized through the polymerization of triazine-containing diamine and diisocyanate. The intramolecular aggregation of triazine rings and urea groups along the macromolecular backbone gives PUAs a significant polymerization-induced emission (PIE). Among the four PUAs, PUA-LP shows a significant fluorescent emission at 450 nm, compared to non/weak fluorescent 2,4-diamino-6-phenyl-1,3,5-triazine and L-Lysine diisocyanate ethyl ester monomers. Additionally, the external factors such as solution concentration, excitation wavelength, and precipitants also play a crucial role in the fluorescence of PUAs. As expected, PUA-LP can selectively recognize and detect Fe3+/Fe2+ ions even in the presence of 12 other metal ions and 10 anions. The limit of detection of PUA-LP to Fe3+/Fe2+ is as low as 1.02 μM (0.06 mg/L) and 0.86 μM (0.05 mg/L), respectively, and far below 0.3 mg/L of the allowable national standard for drinking water by WHO. Furthermore, the quenching mechanism of Fe3+/Fe2+ to PUA-LP is attributed to static quenching caused by the coordination of Fe3+/Fe2+ ions with a coordination ratio of 2:1. Based on PIE, the fluorescent PUA-LP was made into an observable and portable testing paper for detecting Fe3+/Fe2+ ions. Finally, we measured the recovery rate of the actual tap water samples and compared the performance of PIE-active PUA-LP with the other reported fluorescent probes to Fe3+/Fe2+ ions.

Tunable structure and linear viscoelastic properties of poly(glycerol adipate urethane)-based elastomeric composites for tissue regeneration

Elastomeric biocomposites based on poly(glycerol adipate urethane) and hydroxyapatite were fabricated for tissue regeneration. The poly(glycerol adipate urethane) (PGAU) elastomeric composite matrices were obtained by chemical crosslinking of the poly(glycerol adipate) prepolymer (pPGA) with diisocyanate derivative of L-lysine. Two series of composites varying in the amount of L-lysine diisocyanate ethyl ester (LDI) used as a crosslinking agent were manufactured. As a ceramic filler both unmodified and L-lysine surface-modified hydroxyapatite (HAP) particles were used. The novelty of our research consists in the manufactured elastomeric materials and characterization of their linear viscoelastic (LVE) properties. The LVE properties of the composites were investigated by means of dynamic thermomechanical analysis. Frequency sweep and amplitude sweep measurements were performed in shear mode. The influence of the crosslinking agent (LDI) amount, HAP content and surface modification of HAP on the LVE properties of the composites was determined based on the analysis of the master curves of storage (G′) and loss (G″) moduli and of tanδ of the composites. Depending on the amount of LDI, HAP and surface modification, the materials differ in the values of rubber elasticity plateau modulus (G0) and G′ and G″ determined at selected shear frequencies and at the glassy state. G0 ranges from 278 kPa to 3.98 MPa, G′ in the glassy state is within the range of 219 MPa–459 MPa. The G0 values of the PGAU-based composites are within the stiffness range of soft tissue. In view of the choice of HAP as the ceramic component and the G0 values, elastomeric composites have the potential to be used as filling materials in small bone defects (due to their mechanical similarity to osteoid) as well as materials for cartilage tissue regeneration.

Synthesis and Biodegradation Test of a New Polyether Polyurethane Foam Produced from PEG 400, L-Lysine Ethyl Ester Diisocyanate (L-LDI) and Bis-hydroxymethyl Furan (BHMF).

In this paper we produced a bio-based polyether-polyurethane foam PU1 through the prepolymer method. The prepolymer was obtained by the reaction of PEG 400 with L-Lysine ethyl ester diisocyanate (L-LDI). The freshly prepared prepolymer was extended with 2,5-bis(hydroxymethyl)furan (BHMF) to produce the final polyurethane. The renewable chemical BHMF was produced through the chemical reduction of HMF by sodium borohydride. HMF was produced by a previously reported procedure from fructose using choline chloride and ytterbium triflate. To evaluate the degradation rate of the foam PU1, we tested the chemical stability by soaking it in a 10% sodium hydroxide solution. The weight loss was only 12% after 30 days. After that, we proved that enzymatic hydrolysis after 30 days using cholesterol esterase was more favoured than hydrolysis with NaOH, with a weight loss of 24%, probably due to the hydrophobic character of the PU1 and a better adhesion of the enzyme on the surface with respect to water. BHMF was proved to be of crucial importance for the enzymatic degradation assay at 37 °C in phosphate buffer solution, because it represents the breaking point inside the polyurethane chain. Soil burial degradation test was monitored for three months to evaluate whether the joint activity of sunlight, climate changes and microorganisms, including bacteria and fungi, could further increase the biodegradation. The unexpected weight loss after soil burial degradation test was 45% after three months. This paper highlights the potential of using sustainable resources to produce new biodegradable materials.

Renewable adhesives based on oleo-chemistry: From green synthesis to biomedical applications

Polyurethanes (PUs) are known as performing biomedical tissue adhesive materials. Adhesive applications can be based on synthesized PU-based prepolymers with highly reactive isocyanate (NCO) end-chains, which covalently react with surrounding living tissues. In this study, original sustainable macromolecular architectures were designed and tested. Different fully biobased polyfunctional NCO terminated prepolymers were synthesized from cotton oil (CO)-based polyols and different sustainable diisocyanates (l-Lysine ethyl ester diisocyanate (LDI), pentane diisocyanate (PDI) and dimeryl diisocyanate (DDI)). Then, two-component adhesive systems were prepared using the prepolymers and two chain extenders: 1,4-butanediol and 2-hydroxyethyl disulfide, to obtain in this latter case potential stimuli-responsive materials based on the disulfide bonds. Prepolymers' properties such as in-vitro biocompatibility, as well as two-components systems' adhesive behavior on muscle tissue were assessed. From these two-component systems, fully biobased PUs were obtained. The influence of the selected CO-based polyol, the diisocyanate and the chain extender on the physicochemical, thermal and mechanical properties of the corresponding PUs were studied. Moreover, their influence on biocompatibility and properties related to biomedical applications were discussed. The series of PUs exhibited a large range of properties such as Young's moduli at 25 and 37 °C, ranging from 0.4 to 22 MPa, and adequate hydrolytic and enzymatic degradations after nine weeks of incubation. LDI and PDI-based samples showed great interest in the preparation of such biomedical adhesives due to their good biocompatibilities.

A bio-based and non-toxic polyurethane film derived from Luffa cylindrica cellulose and ʟ-Lysine diisocyanate ethyl ester

• The cellulose extracted from Luffa cylindrica can be utilized for synthesizing different polyurethane architectures. • The combined treatment applied on raw Luffa cylindrica causes to increase in hydrophilicity, thermal stability and transition temperatures. • The incorporation of ʟ-Lysine diisocyanate ethyl ester on cellulose of Luffa cylindrica enhances hydrophobicity, thermal properties and biodegradability. • The PUR film achieved is degradable in enzymatic and hydrolytic conditions. This study aims to explore the step-growth polymerization (SGP) between the most abundant biomass-cellulose (LCC) extracted from Luffa cylindrica (LC) and ʟ-Lysine diisocyanate ethyl ester (ʟ-LDI) to be achieved an unprecedented polyurethane network (PUR). The resulting bio-based and non-toxic PUR film is obtained by direct solution casting after SGP. The efficiency of the SGP is examined in detail Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance ( 1 H NMR) spectroscopies, water contact angle (WCA) measurements, thermogravimetric and differential scanning calorimetry analyses (TGA and DSC) by comparing precursors and final film. Moreover, the biodegradation behavior of PUR achieved is evaluated in vitro both hydrolytic and enzymatic media. Based on the conducted analyses, PUR film shows higher hydrophobicity and degradation temperatures compared to raw LC and LCC. Moreover, it is determined that the PUR film more degradable than its precursors in both hydrolytic and enzymatic media. Consequently, the approach developed here is broadly adaptable to other functional isocyanate monomers and will be useful to scientists working on bioplastic applications.

Fully Bio-Based Thermosetting Polyurethanes from Bio-Based Polyols and Isocyanates.

The trend towards the utilization of bioresources for the manufacturing of polymers has led industry players to bring to the market new monomers. In this work, we studied 3 polyisocyanates and 2 polyols with high renewable carbon contents, namely L-lysine ethyl ester diisocyanate (LDI), pentamethylene-diisocyanate (PDI) isocyanurate trimer, and hexamethylene-diisocyanate (HDI) allophanate as the isocyanates, as well as castor oil and polypropanediol as the polyols. These monomers are commercially available at a large scale and were used in direct formulations or used as prepolymers. Thermosetting polymers with Tg values ranging from −41 to +21 °C and thermal stabilities of up to 300 °C were obtained, and the polymerization was studied using NMR, DSC, and rheology. Cured materials were also characterized using FTIR, DMA, gel content, and swelling index determinations. These high bio-based content materials can successfully be obtained and could be used as alternatives to petro-based materials.

Response of Endothelial Cells to Gelatin-Based Hydrogels

The establishment of confluent endothelial cell (EC) monolayers on implanted materials has been identified as a concept to avoid thrombus formation but is a continuous challenge in cardiovascular device engineering. Here, material properties of gelatin-based hydrogels obtained by reacting gelatin with varying amounts of lysine diisocyanate ethyl ester were correlated with the functional state of hydrogel contacting venous EC (HUVEC) and HUVEC's ability to form a monolayer on these hydrogels. The density of adherent HUVEC on the softest hydrogel at 37 °C (G' = 1.02 kPa, E = 1.1 ± 0.3 kPa) was significantly lower (125 mm-1) than on the stiffer hydrogels (920 mm-1; G' = 2.515 and 5.02 kPa, E = 4.8 ± 0.8 and 10.3 ± 1.2 kPa). This was accompanied by increased matrix metalloprotease activity (9 pmol·min-2 compared to 0.6 pmol·min-2) and stress fiber formation, while cell-to-cell contacts were comparable. Likewise, release of eicosanoids (e.g., prostacyclin release of 1.7 vs 0.2 pg·mL-1·cell-1) and the pro-inflammatory cytokine MCP-1 (8 vs <1.5 pg·mL-1·cell-1) was higher on the softer than on the stiffer hydrogels. The expressions of pro-inflammatory markers COX-2, COX-1, and RAGE were slightly increased on all hydrogels on day 2 (up to 200% of the control), indicating a weak inflammation; however, the levels dropped to below the control from day 6. The study revealed that hydrogels with higher moduli approached the status of a functionally confluent HUVEC monolayer. The results indicate the promising potential especially of the discussed gelatin-based hydrogels with higher G' as biomaterials for implants foreseen for the venous system.

Synthesis and characterization of bile acid, poly (ε-caprolactone) and ʟ-lysine diisocyanate ethyl ester based polyurethanes and investigation of their biodegradability properties

A series of environmentally friendly polyurethane (PU) films are successfully synthesized. For this purpose, ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) in the presence of cholic acid (CA) initiator, step-growth polymerization between achieved CA based poly (ε-caprolactone) (CA-PCL) and ʟ-Lysine diisocyanate ethyl ester (ʟ-LDI), and solution casting method were used, respectively. The effect of using different feeding ratios of ε-CL monomer (CA:ε-CL = 1:60, 1:75 and 1:90, by mole) on the properties of PUs are investigated in detail by fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopies, gel permeation chromatography (GPC), water contact angle (WCA) measurements, thermogravimetric and differential scanning calorimetry analyses (TGA and DSC) and mechanical tests, respectively. Moreover, biodegradation tests in the absence or presence of porcine pancreatic lipase are conducted to determine the degradation behaviors of resulted PURs. It has been found that a higher proportion of ε-CL repeating units in the PU backbone cause the improvement in hydrophobicity, thermal and mechanical properties, while leading to the deterioration in degradation behavior. Furthermore, biodegradation studies have led to conclude that CA-PCL-PUs are more degradable in both hydrolytic and enzymatic media compared to PCL-PU synthesized without CA. This study proved to CA, PCL and ʟ-LDI based biodegradable PU films have great potential for application in particularly tissue engineering and wound dressing.

Remarkable diastereomeric effect on thermoresponsive behavior of polyurethane based on lysine and tartrate ester derivatives.

This study describes the long-distance diastereomeric effect on thermoresponsive properties in water-soluble diastereomeric polyurethanes (PUs) composed of an l-lysine ethyl ester diisocyanate and a trimethylene glycol l-/d-tartrate ester, which have differences in spatial arrangements of the ethyl esters in the mirror image. The PUs based on l-lysine and l-/d-tartrate ester, named l-PU and d-PU, were synthesized with various number average molecular weights from 4700 to 13 100. In turbidimetry, l-PU showed a steep phase transition from 100%T to 0%T within about 10 °C at 4 g L−1, whereas d-PU did not change completely to 0%T transmittance even at 80 °C at 4 g L−1. In addition, the thermoresponsive properties of l-PU were less affected by concentration than those of d-PU. This long-distance diastereomeric effect on thermoresponsive behavior between l-PU and d-PU appeared in common among 6 samples with 4700 to 13 100 number average molecular weight. In the dynamic light scattering experiments at each transmittance, the hydrodynamic diameter (Dh) of l-PU increased up to 1000 nm, while the Dh of d-PU remained almost at 200–300 nm. The C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> O stretching vibration of FT-IR spectra showed that d-PU has more hydrogen-bonded ester groups than L-PU. Thus, we speculated that the difference in the retention of polymer chains in the micelle to promote intermicellar bridging generates the long-distance diastereomeric effect.

Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels.

Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the "Hen's egg test on chorioallantoic membrane" (HET-CAM) test and a mouse model.The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants.

Polyester urethane functionalizable through maleimide side-chains and cross-linkable by polylactide stereocomplexes

Sustainable multifunctional alternatives to fossil-derived materials, which can be functionalized and are degradable, can be envisioned by combining naturally derived starting materials with an established polymer design concept. Modularity and chemical flexibility of polyester urethanes (PEU) enable the combination of segments bearing functionalizable moieties and the tailoring of the mechanical and thermal properties. In this work, a PEU multiblock structure was synthesized from naturally derived L-lysine diisocyanate ethyl ester (LDI), poly(L-lactide) diol (PLLA) and N-(2,3-dihydroxypropyl)-maleimide (MID) in a one-step reaction. A maleimide side-chain (MID) provided a reactive site for the catalyst-free coupling of thiols shown for L-cysteine with a yield of 94%. Physical cross-links were generated by blending the PEU with poly(D-lactide) (PDLA), upon which the PLLA segments of the PEU and the PDLA formed stereocomplexes. Stereocomplexation occurred spontaneously during solution casting and was investigated with WAXS and DSC. Stereocomplex crystallites were observed in the blends, while isotactic PLA crystallization was not observed. The presented material platform with tailorable mechanical properties by blending is of specific interest for engineering biointerfaces of implants or carrier systems for bioactive molecules.

Alkynyl-functionalized chain-extended PCL for coupling to biological molecules

Chemical functionalization of poly(ε-caprolactone) (PCL) enables a molecular integration of additional function. Here, we report an approach to incorporate reactive alkynyl side-groups by synthesizing a chain-extended PCL, where the reactive site is introduced through the covalently functionalizable chain extender 3-(prop-2-yn-1-yloxy)propane-1,2-diol (YPD). Chain-extended PCL with Mw of 101 to 385 kg·mol−1 were successfully synthesized in a one-pot reaction from PCL-diols with various molar masses, L-lysine ethyl ester diisocyanate (LDI) or trimethyl(hexamethylene)diisocyanate (TMDI), and YPD, in which the density of functionalizable groups and spacing between them can be controlled by the composition of the polymer. The employed diisocyanate compounds and YPD possess an asymmetric structure and form a non-crystallizable segment leaving the PCL crystallites to dominate the material’s mechanical properties. The mixed glass transition temperature Tg = −60 to −46 °C of the PCL/polyurethane amorphous phase maintains the synthesized materials in a highly elastic state at ambient and physiological conditions. Reaction conditions for covalent attachment in copper(I)-catalyzed azide-alkyne-cycloaddition reactions (CuAAC) in solution were optimized in a series of model reactions between the alkyne moieties of the chain-extended PCL and benzyl azide, reaching conversions over 95% of the alkyne moieties and with yields of up to 94% for the purified functionalized PCL. This methodology was applied for reaction with the azide-functionalized cell adhesion peptide GRGDS. The required modification of the peptide provides selectivity in the coupling reactions. The obtained results suggest that YPD could potentially be employed as versatile molecular unit for the creation of a variety of functionalizable polyesters as well as polyurethanes and polycarbonates offering efficient and selective click-reactions.

In vitro Degradation Analysis of 3D-architectured Gelatin-based Hydrogels

ABSTRACT:Multifunctional biopolymer-based materials are promising candidates for next generation regenerative biomaterials. Understanding the degradation behavior of biomaterials is vital for ensuring biological safety, as well as for better control of degradation properties based on rational design of a material’s physical and chemical characteristics. In this study, we decipher the degradation of a hydrogel prepared from gelatin and lysine diisocyanate ethyl ester (LDI) using in vitro models, which simulate hydrolytic, oxidative and enzymatic degradation (collagenase). Gravimetrical, morphological, mechanical and chemical properties were evaluated. Notably, the hydrogels were relatively resistant to hydrolytic degradation, but degraded rapidly within 21 days (&gt;95% mass loss) under oxidative and collagenase degradation. Oxidative and collagenase degradation rapidly decreased the storage and loss modulus of the hydrogels, and slightly increased their viscous component (tan δ). For each degradation condition, the results suggest different possible degradation pathways associated to the gelatin polypeptide backbone, urea linkages and ester groups. The primary degradation mechanisms for the investigated gelatin based hydrogels are oxidative and enzymatic in nature. The relative hydrolytic stability of the hydrogels should ensure minimal degradation during storage and handling prior to application in surgical theatres.

Toward Fully Bio-based and Supertough PLA Blends via in Situ Formation of Cross-Linked Biopolyamide Continuity Network

Dynamic vulcanization has been demonstrated to be a versatile and efficient way of improving impact toughness of PLA. However, the existing vulcanization routes usually suffer from complicated presynthetic procedures and use of nonrenewable modifiers as well as markedly enhanced melt-viscosity. Herein, using both biomass-derived hydrogenated dimer acid (HDA) and an excess molar amount of l-lysine ethyl ester diisocyanate (LDI) as toughening monomers, we have developed a facile yet highly effective diisocyanate method for the design of fully bio-based PLA blends with excellent impact toughness and melt-flowability. The in situ formation and self-cross-linking of flexible biopolyamide (HDAPA) toughener, as well as its reactive compatibilization with PLA, were accomplished in a single melt-blending step. When incorporating the amount of HDAPA from 15 to 20 wt % or higher, the resulting blends evolved from the network-like morphology to the bi-continuous one with the cross-linked HDAPA network. At HDAPA content higher than 10 wt %, a sharp and persistent brittle–ductile transition occurred with an equilibrium impact strength of over 1200 J/m, and elongation-at-break was over 400%. Moreover, such a tremendous toughening effect was accompanied by low melt-viscosity and enhanced PLA crystallization. The matrix yielding triggered by internal cavitation of percolated HDAPA domains, together with the pull-out of many in situ formed block copolymers located at the interfaces, was found to be the major impact-toughening mechanism. This work offers a novel and facile strategy for fabricating high-performance and fully bio-based polymeric materials.

Synthesis and characterization of biodegradable polyurethanes made from cholic acid and l-lysine diisocyanate ethyl ester

In this work, a series of biodegradable polyurethanes (PURs) based on cholic acid (CA) and l-lysine diisocyanate ethyl ester (L-LDI) that are renewable difunctional building blocks is synthesized by step-growth polymerization. Step-growth polymerizations between CA and L-LDI are conducted at different loading ratios by mole ([CA]/[L-LDI] (n/n) = 1:1; 1:2 and 1:4) to investigate the effect on wettability, thermal, and biodegradable properties of final PURs. The intermediates and resulting PURs are characterized by Fourier transform infrared spectroscopy (FT-IR), water contact angle measurements (WCA), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, biodegradability of obtained PURs is also investigated by conducting enzymatic degradation experiments. The experimental results reveal that PURs having higher L-LDI loading exhibit higher hydrophobic and thermal properties, while lower biodegradable characteristic compared to others. Thus, it is clear that the obtained PURs have great potential for several applications particularly in the fields of drug delivery and tissue engineering requiring biodegradable properties.

Synthesis and properties of soybean oil-based biodegradable polyurethane films

In this study, a series of biodegradable polyurethane films (PU-Fs) is prepared by step-growth polymerization of hydroxylated soybean oil (SBO-OH) and L-lysine diisocyanate ethyl ester (L-LDI) that are renewable-based difunctional building blocks. The influence of loading ratio by weight (SBO-OH/L-LDI (w/w) = 1:0.5; 1:1 and 1:1.5) on the biodegradable, mechanical and thermal properties of final PU-Fs is systematically investigated. In the first step, epoxy groups of epoxidized soybean oil are converted to corresponding hydroxyl functionalities to react with the diisocyanate groups of L-LDI via film casting method at room temperature. The obtained PU-Fs with higher L-LDI loading exhibit higher thermal and mechanical properties as well as more hydrophobic characteristic compared to others. Moreover, biodegradability of resulting PU-Fs is also studied using hydrolytic and enzymatic degradation experiments. Noteworthy, it is found that around 50 and 60% of PU-Fs are degraded by enzymatic and hydrolytic experiments after 12 weeks.

Pluronic-based dual-stimuli sensitive polymers capable of thermal gelation and pH-dependent degradation for in situ biomedical application.

Thermo-sensitive hydrogels are considered ideal for applications in the biomedical fields for their biocompatibility, flexibility, tissue-like water content, and reversible gelation property. By adjusting sufficient hydrophilic-hydrophobic balance in block copolymer structure, thermogel's critical gelation temperature can be modified to be near the physiological temperature, which makes it an appealing candidate for in situ gel depot. In this study, we report successful syntheses of novel multiple block copolymer compounds, denoted as dual-stimuli sensitive polymers (DSSPs), by copolymerizing Pluronic® P104 (7,100 Da) and 2,2-bis(aminoethoxy)propane (BAP) using diisocyanate linkers, L-lysine ethyl ester diisocyanate (DSSP-1) and 1,6-hexamethylene diisocyanate (DSSP-2). Through effective elongation of polymer chain lengths (DSSP-1: 41,760 Da, DSSP-2: 41,230 Da), Pluronic® P104's reversible thermal gelation properties were enhanced, as demonstrated by lowered critical gelation temperatures (DSSP-1: 36°C, DSSP-2: 38.7°C; 15 wt.%) that is near the physiological temperature. Furthermore, integration of acid-labile BAP allowed rapid pH-dependent degradation of the polymer, which was displayed by gel permeation chromatography (GPC) and release profiles of nile red and irinotecan from polymeric micelles and gels, respectively.

Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel).

Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840±120 μm after 4 days, and distributed in the whole scaffold (2 mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55±0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93±1%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration.

In situ foamable, degradable polyurethane as biomaterial for soft tissue repair

Degradable foams which can be inserted endoscopically as liquid or pasty mixtures into soft tissue defects possess a promising potential for the surgical treatment of such defects. The defects can be sealed under in situ foaming and simultaneous material expansion. We developed an in situ foamable (l-lactide-co-ε-caprolactone)-based, star-shaped prepolymer by ring opening polymerization of l-lactide and ε-caprolactone in the presence of meso-erythritol as starter. By conversion of the terminal hydroxyl groups of the formed oligoester with lysine diisocyanate ethyl ester (LDI) an isocyanate-endcapped, reactive prepolymer has been received. Foaming can be initiated by addition of 1,4-diazabicyclo[2,2,2]octane (DABCO), water, LDI and DMSO. By varying the composition of these additives, the foaming and curing time could be varied within a clinically acceptable range. A porosity of approximately 90%, and an average tensile strength of 0.3MPa with elongations of 90% were determined for the foams.In vitro cytotoxicity on cured foams was assayed on 3T3 fibroblasts and demonstrated an excellent cytocompatibility. This was also confirmed in an in vivo study using an established rat model, where prefabricated foams and in situ hardening material were inserted into subdermal skin incisions in parallel. The feature of chronic inflammation was only weakly developed in both groups and slightly more pronounced and persisted for longer time in the group of in situ foamed material. In both groups the foreign materials were vascularized, degraded and substituted by connective tissue. The results encourage to proceed with trials where the materials are used to fill more heavily loaded defects.

Non-toxic polyester urethanes based on poly(lactic acid), poly(ethylene glycol) and lysine diisocyanate

Poly(lactic acid)-based polymers are highly suitable for temporary biomedical applications, such as tissue support or drug delivery systems. Copolymers of different molecular weight based on poly(lactic acid) and poly(ethylene glycol) were prepared by polycondensation, catalysed by hydrochloric acid. A chain-extension reaction with l-lysine ethyl ester diisocyanate was employed afterwards to obtain polyester urethanes with enhanced properties. The GPC results showed that the molecular weights of the products reached about 50,000 g·mol−1 and the hydrolytic progress was rapid in the first 2 weeks; the drop in Mn equalled approximately 70%. Additionally, elemental analysis of the buffer medium proved that hydrolytic degradation was more rapid in the first stage. Tensile-strength testing revealed that ductility increased alongside reduced molecular weight of poly(ethylene glycol), also suggesting that polymer branching occurred due to side reactions of isocyanate. Based on the envisaged biomedical applications for these polymers, cytotoxicity tests were carried out and the cytotoxic effect was only moderate in the case of 100% polymer extract prepared according to ISO standard 10993-12. In their research, the authors focused on preparing metal-free, catalysed synthesis of polyester urethanes, which could prove useful to numerous biomedical applications.