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Emergent Materials
Degradable poly(ester amide)s from olive oil for biomedical applications
Sagar Nilawar
Queeny Dasgupta
Giridhar Madras
Kaushik Chatterjee
Poly(ester amide)s (PEAs) are polymers with both ester and amide bonds in the polymer backbone offering a combination of desirable properties such as degradability of esters and physio-chemical properties of amides that are attractive for biomedical applications. Olive oil (OO) is known to possess anti-inflammatory properties and offers beneficial health effects. Thus, the aim of this work was to develop a novel class of resorbable PEAs from OO for biomedical applications. Cross-linked PEAs were synthesized by melt condensation followed by curing. The chain length of the diacid, molar ratio of the reactants, and curing conditions were systematically varied to yield a library of polymers with tunable properties. FTIR and 1H-NMR revealed the presence of ester and amide bonds in the polymers. Properties such as the water contact angle and storage modulus (which is directly related to the cross-linking density) increased with the increase in the chain length of the diacid as well as the curing time and with the decrease in the molar ratio of diacid to the functionalized precursor. Hydrolytic degradation studies showed that polymers had a wide range of degradation that spanned ≈ 12 to 50% in 1 week. The dye release followed the Korsmeyer-Peppas semi-empirical equation. In vitro cell studies showed that the polymers were cytocompatible. Thus, this work presents PEAs from OO that are promising resorbable biomaterials for biomedical applications.
Poly(ester amide) Olive oil Release kinetics Degradable polymers Cytocompatible
The online version of this article ( https://doi.org/10.1007/s42247-019-00032-w) contains supplementary material, which is available to authorized users.
The last few decades have seen rapid strides in the biomaterials science that have led to the emergence of the third-generation resorbable biomaterials engineered for controlling the biological response to the implanted device. Synthetic biodegradable polymers are particularly attractive for applications such as tissue engineering [1] and drug delivery [2, 3, 4] to minimize the need for a second surgery to remove the implanted device. Biomaterials used in these applications are typically expected to exhibit several key properties such as cytocompatibility, appropriate mechanical properties, controlled degradation, and release properties that are appropriate and preferably tunable to meet the requirements for different tissues and clinical needs. The degradation rate of the scaffold should nearly match the rate of growth of the target tissue [5]. The modulus of the biomaterial is well known to modulate the response of the cells [6, 7, 8]. Hence, the mechanical properties should be tailored accordingly. The release of drugs and biomolecules must be tailored for burst or steady release depending upon the needs of the application [3, 9, 10].
Various polymers such as polyesters, polyanhydrides, poly(ortho esters), poly(ester amide)s (PEAs), and polyurethanes are some of the popular classes of polymers used for biomedical applications [11]. PEAs are a relatively new class of degradable polymers with both ester and amide bonds in their chemical structure [12]. As a result, PEAs possess a combination of desirable properties such as degradability of esters and physio-thermal properties of amides [13, 14]. Biodegradation is a process of breaking down of materials by means of enzymes secreted by bacteria and fungi like microorganisms. Hydrolytic degradation of materials involves breaking of linkage by the attack of water molecules. Hence, the in vivo degradation caused by water without any contribution from living elements is not a biodegradation process. Good physio-thermal properties of PEA arise due to the presence of hydrogen bonding between the amide groups. Owing to the synergistic properties of the ester and amide groups of PEAs, these polymers have received significant attention for biomedical applications in recent years.
Vegetable oils are ester compounds consisting of a glycerol center linked to three saturated or unsaturated fatty acids. Properties of vegetable oils depend upon percentage unsaturation and chain length of the fatty acids [15, 16, 17, 18, 19]. Vegetable oils can be sourced easily, are cost-effective, and can be easily processed during reactions [20, 21]. Further, in various polymerization reactions, it has been shown that vegetable oils act as highly reactive monomers because of the presence of various reactive functional groups such as the carbon–carbon double bond and the glycerol center [22]. Different kinds of monomers can be prepared by modifying these functional groups potentially yielding various polymers for numerous applications [21]. Furthermore, as edible food sources, they are non-toxic and can offer several health benefits. Consequently, vegetable oils provide a viable substitute for petroleum-based non-renewable resources for production of various polymers [23, 24]. PEAs based on various reactants have been used for biomedical applications such as drug delivery [25], gene delivery [26], and tissue engineering [27, 28, 29]. Aside from biomedical use, PEAs are also used in anticorrosive coatings [30, 31, 32, 33], and PEA-based nanocomposites have been developed as antibacterial coatings [34, 35].
Mediterranean diet is widely regarded to be one of the healthiest diets globally, and olive oil (OO) as a key ingredient is believed to offer several health benefits. OO is known to possess anti-inflammatory activity [36] and contains significant amounts of vitamins E and K, which improve bone health [37]. OO is a triglyceride of primarily C18 fatty acids (containing an 18-carbon hydrophobic chain) and with more than 85% of unsaturation [38, 39]. Fatty acids present in olive oil are primarily 55–83% of oleic (C18:1), 3.5–21% of linoleic (C18:2), 7.5–20% of palmitic (C16:0), 0.5–5% of stearic (C18:0), 0–1.5% of linolenic (C18:3), and 0.3–3.5% of palmitoleic (C16:1) [38, 39]. Some polymers have been prepared using OO. Alam and Alandis synthesized poly(ether amide) from OO as an anticorrosive film coating [40]. OO-based polymers are also used as paints, lubricants [41], bioplastics, and elastomers [42].
The objective of the work was to develop a novel class of PEAs for biomedical applications with tunable degradation, mechanical properties, and release. A resorbable biomedical polymer must be cytocompatible and degradable. The selection of reactants depends on the multifunctionality, non-toxicity, and endogeneity to the human metabolic system. OO is multifunctional and eliminated via the β-oxidation pathway from the human body. Likewise, other reactants utilized in this study such as diethylene triamine (DETA) and various diacids are also multifunctional and non-toxic. DETA is cleared out by the renal pathway from the human body, whereas dicarboxylic acids are removed by the β-oxidation pathway to form CO2. To the best of our knowledge, OO-based PEAs have not been reported. We aimed to synthesize a library of PEAs by melt condensation by varying the diacid. These diacids including adipic acid, sebacic acid (decanedioic acid), and dodecanedioic acid are linear dicarboxylic acids of progressively increasing chain length. We have synthesized PEAs by systematically varying the stoichiometric ratio and time of curing of the prepolymer formed after the melt polycondensation reaction. The physicochemical properties were and characterized to assess these polymers for use in biomedical applications.
2 Materials and characterization methods
2.1 Materials
Edible virgin OO (Farrell Premium oil, first cold press) was purchased from the local grocery store. Glacial formic acid (99.8%), conc. sulfuric acid (98%), and hydrogen peroxide (30%) were purchased from Merck, India. DETA (99%) was procured from S.D. Fine Chemicals, India. Various dicarboxylic acids, namely, adipic acid (99%), sebacic acid (99%), and dodecanedioic acid (99%), were procured from Sigma-Aldrich, USA, and used as received. Solvents used in the work include acetone and tetrahydrofuran; all are of reagent grade and obtained from SRL Chemicals, India.
2.2 Synthesis
The synthesis of the PEAs performed in this study is a three-step process (Fig. 1). The first step is the epoxidation of OO. The second step involves ammonolysis and formation of the functionalized precursor, which contains free hydroxyl and amine groups. The third step is melt polycondensation of dicarboxylic acid and functionalized precursor synthesized in the second step to form PEAs. In this step, condensation reaction takes place between free hydroxyl and amine group of the functionalized precursor and carboxyl group of diacid, and water is released as by-product.
Three-step possible reaction schematic of poly(ester amide) synthesis
2.2.1 Epoxidation of olive oil
Epoxidation of OO was performed with peracid method catalyzed by a small amount of concentrated sulfuric acid [43]. Glacial formic acid and hydrogen peroxide were used. The stoichiometric ratio of oil:formic acid:hydrogen peroxide and the duration of reaction were varied to obtain the optimal percentage of epoxidation that was calculated from the ratio of Fourier transform infrared (FTIR) peaks of the epoxy group and the asymmetric methylene group. As described below, the optimized reaction conditions were found to be a molar ratio of 1:3:9 at 55 °C for 7 h. Based on the optimized molar ratio, the amounts of formic acid and oil were taken in a round bottom flask. To this mixture, 2 wt% of conc. sulfuric acid was added. Subsequently, hydrogen peroxide was added drop by drop to the reaction mixture. After completion of the reaction, the excess water in the product was removed by filtration and the product was washed with ultrapure water to remove excess acid. The product was dried at 60 °C to get epoxidized OO (EOO). The completion of reaction was marked by color change of the reaction mixture from mustard yellow to light lemon yellow.
2.2.2 Synthesis of the functionalized precursor
Ammonolysis of EOO was accomplished by reacting with DETA in a two-neck round bottom flask to synthesize the functionalized precursor [44]. The reaction was performed under continuous nitrogen purging at 150 °C. EOO and DETA were taken at a 1:3 molar ratio, and the reaction was continued until both epoxy and carbonyl ester stretch peaks in the FTIR spectra disappeared and until the reaction mass attained a jelly-like consistency at around 3 h. The reaction mass started to dissolve in DI water at ambient temperature with vigorous washing; hence, it was washed slowly with ice-cold DI water to remove the unreacted triamine. The color of the product was reddish yellow, and it was soluble in tetrahydrofuran.
2.2.3 Melt polycondensation to synthesize poly(ester amide)s
The functionalized precursor synthesized in the second step above and the dicarboxylic acid (adipic acid, sebacic acid, or dodecanedioic acid) were taken in a specific molar ratio in a one-neck round bottom flask. Catalyst-free melt polycondensation was performed at 150 °C under nitrogen environment for 30 min. A liquid nitrogen trap attached to vacuum at − 700 mmHg was used for 2 h for the elimination of water, which formed in the condensation reaction as a by-product. The prepolymers were subsequently post-polymerized at 130 °C under − 700 mmHg in a vacuum oven for 8 days to obtain cured cross-linked polymers. The cured polymers were washed with ultrapure water at 60 °C to remove unreacted reactants.
Note that PEAs of the functionalized precursor reacted with adipic acid (A), sebacic acid (S), and dodecanedioic acid (D) in a molar ratio of 1:5 cured for 8 days will be hereafter referred to as PA5, PS5, and PD5, respectively. The molar ratio of the functionalized precursor and dicarboxylic acid was also varied for sebacic acid to 1:3 and 1:7, and these polymers are referred as PS3 and PS7, respectively. Additionally, one batch of prepolymers of PS5 was cured for 10 days instead of 8 days and will be referred as PS5-10d.
2.3 Physical and chemical characterization
Chemical characterization of PEAs and intermediates was done by Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (1H-NMR) spectroscopy. Thermal properties of polymers were obtained by differential scanning calorimetry (DSC), and mechanical properties were obtained by dynamic mechanical analysis (DMA). Surface water wettability was done by contact angle goniometry. Additional properties relevant to biomedical applications such as swelling behavior, degradation, and dye release studies were performed.
2.3.1 FTIR spectroscopy
A PerkinElmer Frontier FT-NIR/MIR spectrometer was used to obtain FTIR spectra. For FTIR analysis, the universal attenuated total reflectance (uATR) mode was used. Each spectrum obtained was an average of 12 scans which were recorded over a range of 4000–650 cm−1 with a resolution of 4 cm−1.
2.3.2 1H-NMR spectroscopy
A 400 MHz Bruker Avance NMR spectrometer was used for 1H-NMR analysis. Approximately 5 mg of sample was dissolved in 600 μL of deuterated solvent for analysis. OO and EOO were dissolved in deuterated CDCl3, whereas the functionalized precursor and prepolymer of PS5 were dissolved in d6-DMSO.
2.3.3 MALDI-TOF spectroscopy
The molecular weight of reaction species was obtained by MALDI-TOF spectroscopy on an UltrafleXtreme MALDI TOF/TOF (Bruker Daltonics). In this measurement, 1 mg of samples was dissolved in 1 mL of 1:1 acetonitrile:dimethylformamide solution.
2.3.4 Differential scanning calorimetry
A differential scanning calorimeter (Q2000, TA Instruments) was used to determine thermal properties of the cured PEAs. 3 to 5 mg of samples were subjected to a heating-cooling-heating cycle from − 50 to 150 °C. A temperature ramp of 10 °C/min and nitrogen flow of 50 mL/min were used. The first heating cycle was disregarded as it is influenced by the thermal history resulting from processing of the polymer. The second heating cycle was considered for analysis.
2.3.5 Dynamic mechanical analysis
A Dynamic mechanical analyzer (Q800, TA Instruments) was used to characterize the mechanical properties of polymers in the film tension mode using rectangular cured polymer films (30 mm × 5 mm × 1 mm dimensions). Samples were subjected to a dynamic frequency sweep ranging from 1 to 100 Hz with preload force of 0.01 N and amplitude of 15 μm at isothermal temperature of 37 °C.
2.3.6 Surface water wettability
Surface water wettability of the polymers was characterized by measuring the static contact angle using a contact angle goniometer (Data Physics). One microliter of ultrapure water was placed on the flat surface of the cured polymer samples. Static contact angle measurements were made 3 s after the water droplet was placed.
2.3.7 Swelling behavior
The swelling-deswelling studies were performed to calculate the % swelling ratio (%SR) of the cross-linked PEAs. Disc-shaped samples (4.5 mm diameter × 1 mm thickness) were punched from drop-casted films of the cured PEAs. The discs were immersed in 20 mL of acetone (non-solvent) at 37 °C and allowed to swell to obtain constant mass (Ms). Thereafter, the discs were dried at 37 °C to a constant mass (Md). The % swelling ratio was calculated by the following Eq. 1:
$$ \%\mathrm{Swelling}\ \mathrm{ratio}=\frac{M_{\mathrm{s}}-{M}_{\mathrm{d}}}{M_{\mathrm{d}}}\times 100 $$
2.3.8 Hydrolytic polymer degradation
Similar to the swelling behavior studies described above, circular polymer discs were punched out of cured polymer films. Discs were weighed (initial mass = Mo) and placed in nylon mesh bags. Then bags were immersed in 20 mL of phosphate-buffered saline (PBS) solution (pH = 7.4) and kept at 37 °C and 100 rpm in an incubator shaker. After a specific time interval, nylon bags were taken out, washed with distilled water, and dried in a hot air oven for 12 h to attain constant dry mass, and discs were weighed (Mt) after degradation for time period t. PBS was replaced every 24 h to avoid changes occurring due to pH.
The percentage mass loss for time period t calculated based on the following Eq. 2:
$$ \%\mathrm{mass}\ \mathrm{loss}=\frac{M_{\mathrm{o}}-{M}_t}{M_{\mathrm{o}}}\times 100\kern0.50em $$
2.3.9 Dye release studies
Two dyes, namely, rhodamine B (RB) (hydrophilic) and rhodamine B base (RBB) (hydrophobic), were used for the dye release studies. The prepolymer was dissolved in tetrahydrofuran followed by addition of 2% dye to solution. The solvent was removed by drying in a hot air oven. Dried dye-prepolymer mixture was cured in a manner similar to the normal cured samples in a vacuum oven at 130 °C under − 700 mmHg vacuum. Discs were punched from the cured dye-polymer samples in a manner similar to swelling studies. Discs were immersed in 20 mL of PBS solution and were kept in a shaker incubator at 37 °C and 100 rpm. After specific time intervals, PBS containing released dye was collected. The amount of dye released in PBS was obtained by measuring absorbance at 553-nm wavelength.
2.4 Cell studies
MC3T3-E1 (ATCC, USA) subclone 4 mouse calvarial preosteoblasts were used to assess the cytocompatibility of polymers in vitro. This cell line has been used in several studies to test in vitro cytocompatibility of polymers [45]. Cells were cultured in α-minimum essential medium (α-MEM, Sigma) supplemented with 1% antibiotics (Sigma) and 10% fetal bovine serum (Gibco, Life Technologies) at 37 °C and 5% CO2. Cured polymer discs of 4.5 mm diameter and 1 mm thickness were punched similar to swelling studies. These discs were sterilized using ethanol and UV for 30 min each. Then, 100 mg of polymer discs of each PEA was immersed in 5 mL of complete culture medium in centrifuge tubes, and tubes were kept in an incubator at 37 °C and 5% CO2 for 24 h. Thereafter, the discs were removed to obtain conditioned medium that contained the degradation products of the PEAs.
Two thousand cells were seeded per well of a 96 well plate containing 200 μL of complete culture medium and cultured as described above. The cells were allowed to attach to the surface of the well plate for 12 h. Subsequently, the culture medium was replaced with conditioned medium to check the effect of the degradation products on the cells.
Cell viability and proliferation was assessed on the 1st and 3rd day after adding conditioned medium by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay (Sigma-Aldrich) following supplier's recommended procedures. The conditioned medium was replaced with medium containing 1 mg/mL MTT solution and incubated for 3 h at 37 °C. This solution was further replaced by 200 μL of DMSO to dissolve the formed formazan crystals. The absorbance of the solution was measured using a microplate reader (Synergy HT, BioTek instrument) at 570 nm. As a positive control, cells were treated in fresh culture medium. All measurements were performed in quadruplicates for each PEA and the data are presented as mean ± deviation (S.D.) for n = 4. Statistically significant differences were determined from analysis of variance also called as ANOVA with Tukey's test. Differences were considered statistically significant for p < 0.05.
The morphology of the cells was examined by fixing the cells at day 1 and day 3 in 3.7% formaldehyde (Merck) solution for 30 min and imaged in a bright-field microscope (Olympus).
3 Results and discussion
3.1 Polymer synthesis
Figure 1 schematically presents the different steps of the synthesis. In the epoxidation step, the reaction parameters including the molar ratio of OO:formic acid:hydrogen peroxide and the reaction time were systematically varied to result in the maximum epoxidation of OO. In the subsequent ammonolysis step, the highly reactive DETA breaks down the epoxy ring along with the glycerol center of EOO. This breaking of the glycerol center results in the introduction of other functional groups and thus increases the cross-linking [44]. The functionalized precursor was reacted with adipic acid, sebacic acid, or dodecanedioic acid in a molar ratio of 1:5 to check the effect of the chain length. To check the effect of the molar ratio, the functionalized precursor was reacted with the sebacic acid in a molar ratio of 1:3, 1:5, or 1:7. Curing time for PS5 was also varied from 8 to 10 days to check the effect of curing time. Note that a further increase in curing time was observed to cause charring of the polymer. All the prepolymers were soluble in tetrahydrofuran. However, the cured PEAs did not dissolve in solvents because of their cross-linked structure. Percentage yield for the epoxidation reaction and the ammonolysis reaction was ≈ 65% and ≈ 75%, respectively. The yield for the melt condensation reaction varied between 80 and 90% for the various PEA prepolymers.
3.2 Structural analysis
FTIR spectroscopy was carried out at each step of the reaction to confirm the formation of the product. FTIR spectra of OO (Fig. 2a) show the =C–H stretch unsaturation peak at 3006 cm−1 and the C=O carbonyl ester stretch peak of the glycerol center at 1743 cm−1. The peaks corresponding to C–C stretching and the asymmetrical and symmetrical –CH2 stretching are observed at 1157, 2923, and 2853 cm−1, respectively. In the EOO spectra (Fig. 2a), the =C–H stretch peak is absent after epoxidation whereas the new –C–O epoxy stretch peak is seen at 826 cm−1. These observations confirm that the epoxidation reaction caused the conversion of unsaturated C=C to epoxy groups.
FTIR spectra of a OO and EOO, b EOO and functionalized precursor, c PS5 prepolymer, d PEAs with varying stoichiometry, and e PEAs with varying curing time
Figure 2b shows the FTIR spectra of the functionalized precursor. Both the C=O carbonyl ester stretch peak at 1743 cm−1 and epoxy stretch peak at 826 cm−1 are completely absent indicating that DETA reacted with both the epoxy group and the glycerol center of OO. The C=O carbonyl stretch peak and –N–H stretch peak of amide at 1647 and 1553 cm−1, respectively, show the formation of amide groups due to the ammonolysis reaction. A broad new peak at 3290 cm−1 of –O–H and –N–H stretching can be observed.
The FTIR spectra in Fig. 2c show the ester linkage carbonyl stretching vibration at 1721 cm−1 for the PEA prepolymer. No changes in the peak positions are observed for carbonyl at 1646 cm−1 and –N–H at 1549 cm−1 of amide. The –C–O stretch peak of ester is observed at 1170 cm−1. All these peaks confirm the presence of the amide and ester groups in the PEA.
The FTIR spectra in Fig. 2d show the effect of the molar ratio of sebacic acid and functionalized precursor on the carbonyl stretching of ester linkage of PEAs. It is observed that the intensity of the carbonyl ester moiety vibration at ≈ 1727 cm−1 decreases with the increase in the molar ratio. Whereas PS3 and PS5 show sharp peaks, PS7 displays a shoulder peak at ≈ 1730 cm−1 and a prominent peak at ≈ 1693 cm−1, which is specific to ester linage carbonyl stretching vibration of sebacic acid. This indicates a lower extent of esterification. The possible reason could be the higher amount of sebacic acid reduces the rate of conversion to esters and remains unreacted.
Figure 2e compiles the FTIR spectra of PEAs cured for various durations of curing. The intensity of the carbonyl peak of the ester increases gradually as curing time increases. Also, the carbonyl peak shifts towards 1730 cm−1 with the increase in curing time, and the amount of esterification increases.
Furthermore, NMR spectroscopy was also used for structural analysis of various molecules formed during reaction. Figure 3a shows NMR spectra for OO. In this spectrum, peaks at around 0.9 ppm and 4.1 ppm correspond to the protons of the methylene group present at the end of the molecule and the glycerol center present in the molecule. The peak around 5.2 ppm may be ascribed to the proton of C=C carbon double bond. The proton peaks associated with the glycerol center and methylene units are also present in the NMR spectrum of EOO. Before epoxidation, the integral of peak around 5.2 ppm exhibits the value of 5 whereas after epoxidation, the integral value gets reduced to 1. This specifies that some double bonds did not react possibly due to steric hindrance. The new peak around 2.8 ppm corresponds to the epoxy proton, which confirms the decrease in the number of the C=C carbon double bond and formation of the epoxy group in the molecule (Fig. 3b).
NMR spectra for a OO, b EOO, and c sebacic acid based prepolymer
The NMR spectrum of PEA is shown in Fig. 3c. The peak of Cγ proton of the ester group is observed at around 1.2 ppm whereas the signals corresponding to the Cβ proton of ester moiety is observed at 1.4 ppm and the Cα proton peak at 2.1 ppm due to the shielding effect of the methyl group. The large peak around 3.6 corresponds to the proton of the free hydroxyl group, which is abundantly present in the prepolymer. As the cured PEAs are insoluble in solvent, NMR characterization was not performed on the cured polymers.
3.3 Molecular weight determination
MALDI TOF MS can determine absolute molecular weights of compounds/oligomers. The absolute molecular weight of OO is 913 m/z. The spectra of EOO show a prominent peak at m/z = 955 Da. Further, the spectra of prepolymer PS5 show two prominent peaks: the largest peak at m/z = 1003 Da and the second prominent peak at m/z = 847 Da. The first peak attributed to the prepolymer in which three diacids attached. The second prominent peak attributed to prepolymer with two diacid groups attached. The highly viscous nature of the reaction mixture during melt condensation reaction is the possible reason for this occurrence. The molecular weight of the cured polymers cannot be analyzed as the polymers are insoluble in solvent.
3.4 Thermal properties
DSC thermograms reveal that all the PEAs do not have melting or crystallization peaks indicating that these cross-linked PEAs are amorphous in nature. DSC results show a decrease in the glass transition temperature (Tg) from 12.6 °C for PA5 to 6.8 °C for PD5. Tg decreases with the increase in the chain length. Short-chain diacid forms cross-links in close vicinity to each other, which results in the formation of a rigid network. The closeness of the cross-links hampers the chain movement; hence, Tg of the short–chain length diacid-based polymer PA5 is higher than that of polymers based on longer chain length diacids. A similar trend was observed in PEAs prepared from poly(ethylene terephthalate) and various diacids [46] as well as in the family of PEAs formed by α-amino acid, sebacoyl chloride, and diols of varying chain length [27].
PS3, PS5, and PS7 have Tg values of 0.5 °C, − 2.5 °C, and − 11.5 °C, respectively (Table 1). Tg of PEAs decreases with the increase in the stoichiometric ratio. The extent of esterification is more in PS3 as compared with PS7 resulting in a more rigid network in PS3. Consequently, PEAs with a lower stoichiometric ratio of diacid show higher Tg. Curing causes formation of cross-links between the polymeric chains; hence, the rigidity of the network structure increases with curing time. Consequently, the movement of polymer chains is restricted and thus Tg increases. Tg of PS5 is − 2.5 °C and marginally changes to 1.5 °C for PS5-10d. A similar trend was observed for the amino alcohol (1,3-diamino-2-hydroxypropane)–based PEAs when the curing time was varied [47].
Physical properties of different PEAs
Tg (°C)
Storage modulus (MPa) at 1 Hz
Contact angle (°)
% swelling ratio
23.92 ± 0.52
− 2.5
− 11.5
PS5-10d
18.4 ± 1.09
3.5 Mechanical properties
Storage modulus of the various PEAs is listed in Table 1. The values are comparable to those of soft tissues of the human body such as the human bladder (0.25 MPa) [48] and those of intermediate stiffness such as the articular cartilage in the knee (2.13 to 5.13 MPa) [49] suggesting that these PEAs could find use in the regeneration of such tissues. The trend for the storage modulus with change in the chain length of diacid is as follows: PA5 < PS5 < PD5. Storage modulus scales with the cross-linking density of polymers. The storage modulus of the 8-day cured PS5 is 0.52 MPa compared with 0.70 MPa for PS5-10d, which may be attributed to the increase in cross-linking density with the increase in curing time. Similar result was observed in the family of PEAs of poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) with varying curing time [47]. The storage modulus increases as the stoichiometric ratio of sebacic acid decreases in the following order: PS3 > PS5 > PS7. This is likely because the extent of esterification is less as the molar ratio of sebacic acid increases resulting in a less cross-linked network. A similar kind of observation was cited by Bettinger et al. for PEAs of the poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) family [47] and by Cheng et al. for poly(glycerol sebacate)-based PEAs [50]. The values of the loss modulus are lower than the storage modulus for all the polymers, which indicates all these PEAs are elastomeric in nature and could be suitable for tissue regeneration applications.
3.6 Surface water wettability
Sessile drop water contact angles of PEAs are tabulated in Table 1 and indicate that all the polymers are hydrophobic in nature. The contact angle increases from 97 to 113° for PA5 to PD5 with the increase in the aliphatic chain length of the dicarboxylic acid. Hydrophobicity of the diacid increases with the increase in the aliphatic chain length as a greater number of non-polar hydrophobic methylene groups increases in the diacid. Curing also increases the hydrophobicity of the polymers. Shorter curing time results in the lower extent of esterification resulting in the presence of more free hydroxyl groups.
The contact angle for PS3, PS5, and PS7 is 114°, 107°, and 99°, respectively. An increase in the stoichiometric ratio of sebacic acid resulted in increased water wettability of the polymers. The extent of esterification is lowest in PS7; hence, more free hydroxyl groups are present on the surface, which makes PS7 the most hydrophilic among the three polymers. A similar trend was observed in PEAs formed by dimethyl adipate, 1,4-butanediol, and bisamide-diol [51] with varying molar ratio.
3.7 Swelling studies
Acetone is a hydrophilic solvent and a non-solvent for the prepolymers. So, it was used for assessing the swelling behavior. Most of the biomedical application requires materials having a low swelling ratio upon hydration. Equilibrium swelling theory suggests that the solvent will infuse into the cross-linked polymer until the chemical potential of the solvent becomes equal outside and inside [52]. Swelling increases when the polymer allows more fluid influx such that more cross-linked polymers swell less. Hence, the % swelling ratio (%SR) scales with the hydrophilicity and inversely with the cross-linking density of the polymer. Consequently, an increase in the chain length of diacid shows a decrease in %SR of PEAs. PA5 shows %SR of 24% whereas it is 17.6% for PD5 (Table 1). In case of PEAs formed by reaction of poly(glycerol-sebacate) with ethylenediamine (2C), hexamethylenediamine (6C), and 1,12-diaminododecane (12C), a similar kind of decreasing trend was noted with chain length [50]. Curing causes more cross-linking so that PS5-10d shows less %SR than PS5. An increase in the stoichiometric ratio of sebacic acid shows greater %SR. PS3, PS5, and PS7 show %SR of 17.6%, 20.3%, and 24.6%, respectively. This is likely because an excess amount of dicarboxylic acid lowers the conversion rate to ester resulting in a less cross-linked network. It was reported that PEAs synthesized by reacting poly(glycerol-sebacate) with various molar ratios of 1,5-diamino-2-methylpentan showed decreasing %SR with the decrease in the molar ratio [50].
3.8 Degradation properties
For tissue engineering and drug delivery applications that involve the use of resorbable biomaterials, it is critical to assess the rate of polymer degradation. Degradation studies show that the degradation rate progressively decreases from PA5 to PD5. PA5 degrades fastest and disintegrates into pieces after 3 days whereas PD5 shows mass loss of ≈ 17% in 7 days (Fig. 4a). PS5 shows an intermediate rate of degradation and undergoes 21% mass loss in 7 days. Degradation depends primarily on the hydrophobicity and cross-linking density of the polymers. As the chain length of diacid increases from PA5 to PD5, the polymer becomes more hydrophobic, as discussed above. A similar kind of decrease in mass loss was noted when bisamide diol and 1,4-butane diol reacted with lower chain length ethane diol and higher chain length butane diol to form a family of PEAs [51]. The availability of water in the cross-linked polymer for degradation of the hydrolytically labile ester bond depends upon hydrophobicity of the polymer. It has been observed that the degradation of polyesters results in the deposition of diacids on the surface of the polymer. Lower chain diacids are more soluble in water than higher chain diacids [53, 54]. Consequently, there is more accumulation of diacid on the surface of the degrading PD5 as compared with PA5. This deposition restricts the further ingress of water to the vicinity of the ester bonds and eventually decreases the degradation rate. FTIR analysis of the degraded samples reveals a progressive decrease in the intensity of the carbonyl ester peak at around 1727 cm−1 with the increase in the duration of degradation of PEAs (Fig. S1 in the supplementary material).
Hydrolytic degradation profile showing temporal mass loss of a PEAs with varying chain length of diacid, b PEAs of varying stoichiometry, c PEAs of varying curing time, and d PS5 in different pH conditions. Data points are plotted as mean ± S.D. for n = 3
For the different stoichiometric ratios of sebacic acid, degradation of PEAs increased with the increase in the stoichiometric ratio. PS3 displays the slowest degradation with only 13% mass loss in 7 days whereas mass loss for PS5 and PS7 is 21% and 32%, respectively (Fig. 4b). The increase in degradation from PS3 to PS7 can be attributed to the decrease in cross-linking, which allows more infusion of water molecules into the polymer network. The family of PEAs formed by reacting various ratios of 1,3-diamino-2-hydroxypropane, polyol, and sebacic acid shows a similar trend in mass loss [47]. The 8-day cured PS5 shows faster degradation compared with PS5-10d as a result of higher cross-linked structure of PS5-10d than PS5 (Fig. 4c). In higher cross-linked structure, diffusion of water is more difficult than less cross-linked structure which affects the degradation rate. A similar kind of decrease in mass loss was noticed in poly(ester amide)s of poly(1,3-hydroxypropane-co-polyol sebacate) family. In both studies, a 24 h cured polymer shows higher mass loss compared with a 48 h cured polymer of the same formulation [47, 55].
pH in vivo can vary across different tissues or as a result of pathophysiological conditions. So, it is important to study the effect of pH on the degradation rate of PEAs. In this study, degradation of PS5 was analyzed under acidic, neutral, and basic pH conditions. The degradation rate is highest in basic medium (pH = 9.0), intermediate in neutral PBS (pH = 7.4), and lowest in acidic medium (pH = 3.2). As shown in Fig. 4d, PS5 degrades 13% in acidic medium, 21% in neutral PBS, and 28% in basic buffer in 7 days. The hydrolysis of the ester bond is catalyzed in basic medium [56]. Also, the solubility of the degradation product of ester, i.e., the diacid varies with pH. Diacids have the highest solubility in basic buffer and least in acidic buffer. Thus, the accumulation of diacid on the polymer surface is highest in acidic buffer, which hinders the subsequent interaction of water with the polymer and decreases the degradation rate.
3.9 Release properties
Drug and/or biomolecules can be incorporated in degradable polymers for controlled release. We studied the release of two dyes to understand the controlled release behavior of the polymers. The dye release profiles are similar to the polymer degradation profile. In the case of different chain lengths of diacid, PA5 shows the fastest dye release, PS5 shows intermediate, and PD5 shows the slowest release for both hydrophilic RB and hydrophobic RBB dyes (Fig. 5a, b). RB dye is released much faster than RBB dye because RB is more hydrophilic. A total of 97%, 89%, and 70% of RB are released from PA5, PS5, and PD5, respectively, whereas 91%, 80%, and 62% of RBB are released from PA5, PS5, and PD5, respectively, in 7 days duration. Dye release is faster from the less cured polymer than from the more cured polymer as shown in Fig. 5c, d. PS5 and PS5-10d release 89% and 83%, respectively, of RB dye in 7 days, whereas 80% and 71%, respectively, of RBB dye are released. These trends can be attributed to the differences in cross-linking with change in curing time. PS7 releases 95% of RB whereas 63% released from PS3. For RBB, 90% release is seen from PS7 and 58% from PS3 in 7 days as shown in Fig. 5e, f. So, the dye release increases in both dyes with the increase in the stoichiometric ratio. The reason behind this trend is due to the decrease in cross-linking with the increase in the molar ratio of sebacic acid.
Dye release profile of a rhodamine B base and b rhodamine B for PA5, PS5, and PD5, c rhodamine B base and d rhodamine B for PS5 and PS5-10d, e rhodamine B base and f rhodamine B for PS7, PS5, and PS3. Data points are plotted as mean ± S.D. for n = 3
The release of dye from the cross-linked polymer system depends upon various factors such as the nature of the dye, hydrophobicity of the polymer, solvability of the dye in the dispersion medium, uniformity of dispersion of the dye in the polymer matrix, interaction between dye and matrix, and most importantly on the degradation behavior of the polymer matrix in the case of covalent bonding between dye and polymer. In this case, the dyes contain the carboxyl group and methoxy group, which can bond with the free carboxyl, hydroxyl, or amine groups of the prepolymer during curing, and so it is likely that dyes were linked covalently to the polymer matrix. Hence, dye release follows a trend similar to that of degradation. All the polymers are hydrophobic in nature, as discussed above, so that the hydrophobic dye has more interaction with the polymer as compared with the hydrophilic dye. The hydrophilic RB dye is more water-soluble than the hydrophobic RBB dye resulting in faster release of RB compared with RBB from all the PEAs.
The dye release can be modeled using the semi-empirical equation proposed by Korsmeyer et al. [57]. This semi-empirical equation is primarily used to analyze the drug dissolution profile from polymeric systems. The semi-empirical relation is written as,
$$ \frac{M_t}{M_{\infty }}=k{t}^n $$
where Mt is the amount of dye release at time t, M∞ is the amount of dye released after infinite time, i.e., the total amount of dye released, k is the rate coefficient of dye release, and n signifies the release exponent. It can be rewritten as
$$ \ln \left(\frac{M_t}{M_{\infty }}\right)=\ln (k)+n\ln t $$
For various PEAs, the log-log plot of fractional release (Mt/M0) vs. time is linear with ln(k) as the intercept and the release exponent n as the slope, as shown in insets of Fig. 5 for each graph. The values of k decrease with the increase in the chain length of diacid, i.e., from PA5 to PD5 for both RB and RBB. The values of k obtained for RBB dye release are 14.42, 2.15, and 0.90 h-n for PA5, PS5, and PD5 respectively, and those for RB dye release are 15.71, 3.68, and 2.12 h-n, respectively. The decrease in k values for both dyes with the increase in the chain length of diacid shows slower release of dyes. It is also observed that the k value for the individual polymer is higher in the case of RB compared with the RBB dye, which is similar to the dye release data. The values of n increase with the increase in the chain length of diacid for both RBB and RB dyes. In the case of both dyes, the value of n is greater for PS5-10d than PS5. The values of k for RBB release of PS5 and PS5-10d are 2.15 and 1.48 h-n, respectively, and for RB release of PS5 and PS5-10d are 3.68 and 3.26 h-n, respectively. This indicated that the value of k decreases with increasing curing time for both RBB and RB dyes. For different molar ratios, values of k increase with the increase in the molar ratio, i.e., from PS3 to PS7. The values of k for RB release are 2.66, 3.68, and 4.79 h-n for PS3, PS5, and PD5, respectively, and for RBB release are 2.06, 2.15, and 3.45 h-n for PS3, PS5, and PS5-10d, respectively. The values of n marginally increase with the decrease in the molar ratio for both dyes. The polymers will show non-Fickian/anomalous release for n values greater than 0.45 [58]. For all the PEAs, a value of n is greater than 0.45; hence, they follow anomalous diffusion behavior.
3.10 Cytocompatibility studies
Figure 6 compiles the cytocompatibility results determined using the MTT assay after treating MC3T3-E1 cells with conditioned medium containing the polymer degradation products. Oxidoreductase enzymes present only in viable cells reduce MTT into water-insoluble purple formazan, which is dissolved in DMSO for quantification spectrophotometrically. For day 1, cell viability for conditioned medium from PS3, PS5, or PD5 was marginally lower but not significantly different (p > 0.05) than the control (fresh medium). In contrast, the viability was significantly lower (p < 0.05) for media from PA5, PS5-10d, or PS7. Note that for all the PEAs, the absorbance values increased from day 1 to day 3 showing that the cells are proliferating when cultured in conditioned medium from the different PEAs. At day 3, absorbance values for all PEAs except PA5 are not significantly different from the control. As described above, PA5 degrades faster than the other polymers and the degradation products of PA5 (adipic acid) dissolve more rapidly than other long-chain acids which can increase the acidic nature of the cell culture medium, thereby compromising cell viability. However, the effect is limited, and the cells continue to proliferate for all the polymers suggesting that the products are not cytotoxic and could be useful for biomedical applications. A similar trend was observed for a family of polyesters and PEAs prepared using diacids of various chain lengths where the faster degrading polymers reduced cell viability as a result of the increased acidity [59]. When implanted, it is envisaged that the flow of bodily fluids around the implant will likely reduce the local acidity.
Cytocompatibility of various PEAs assessed by MTT assay for day 1 and day 3. The asterisk (*) mark above the bars shows that the PEAs are statistically significant (p < 0.05) compared with the control (fresh medium) for that given day. Data are shown as mean ± S.D. for n = 3
Representative bright-field images presented in Fig. 7 reveal the cell morphology. The cells in the control and the conditioned media for all the polymers exhibited a characteristic fibroblast-like morphology. Cells appear healthy and well spread at day 1 and day 3 for all the PEAs and control further suggesting that the PEAs are not cytotoxic. Thus, OO-based PEAs prepared here can be developed further as resorbable materials for various biomedical applications.
Optical bright-field micrographs of MC3T3-E1 cells a treated with fresh medium and b treated with conditioned medium of PD5 at × 10 magnification on day 1
In this study, we have successfully synthesized a family of PEAs based on OO. Various PEAs with tunable degradation, mechanical, and release properties were synthesized by systematically varying the chain length of dicarboxylic acid, stoichiometric ratio of dicarboxylic acid and functionalized precursor, and curing time of the prepolymer. All the polymers are observed to be hydrophobic in nature. Along with the above factors, degradation also depends upon pH of the dispersion medium. Dye release of the synthesized PEAs follows the Korsmeyer-Peppas semi-empirical equation. These degradable polymers are shown to be cytocompatible in vitro. Owing to their non-toxic nature, these polymers could be used as resorbable materials for biomedical applications.
The authors would like to acknowledge NMR Research Centre of IISc regarding NMR analysis and Proteomics facility, Molecular Biophysics Unit, IISc, for MALDI TOF MS analysis.
Funding from the Department of Biotechnology, India (DBT), for the Bioengineering and Biodesign Initiative Phase 2 is gratefully acknowledged.
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ESM 1 (DOCX 153 kb)
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© Qatar University and Springer Nature Switzerland AG 2019
1.Department of Materials EngineeringIndian Institute of ScienceBangaloreIndia
2.Centre for Biosystems Science and EngineeringIndian Institute of ScienceBangaloreIndia
3.Department of Chemical EngineeringIndian Institute of ScienceBangaloreIndia
Nilawar, S., Dasgupta, Q., Madras, G. et al. emergent mater. (2019). https://doi.org/10.1007/s42247-019-00032-w
Received 27 February 2019
DOI https://doi.org/10.1007/s42247-019-00032-w
Publisher Name Springer International Publishing


text:
Home / Statement from Mocha OB on Black Maternal Health Week and the Recommendations for Black Women Health Initiatives
Statement from Mocha OB on Black Maternal Health Week and the Recommendations for Black Women Health Initiatives
Jasmin Lee
Mocha OB, a group comprised of over 500 female OB/GYNs, OB trained Family Practice Physicians and Cardiologists of color have been working all week in various activities and have issued the following statement regarding Black Maternal Health week:
"As women of color, we are acutely aware of the crisis facing black women in pregnancy. Black women are dying in childbirth at a rate 4 times greater than any other ethnicity. As OBGYNs, we are on the front lines of the fight to turn this statistic around. Every day we work tirelessly to save the lives of pregnant women whose voices are not heard and whose lives are not valued. The systems that are currently in place do not adequately address the needs of the women in the black community to allow them to fully partner in their health and improve their outcomes. Not only are we physician providers, we have been patients with first-hand experience in existing barriers to our wellness. Until now, our input as black female PHYSICIANS have not been included in any of the discussions to address this healthcare crisis.
We are of the collective opinion that a TEAMeffort is needed to turn the tide towards well-being.
T- Timeliness: We believe that EARLY access to healthcare to optimize health prior to pregnancy is critical. It is necessary that states provide Medicaid expansion and healthcare facilities in rural and urban communities to diagnose and treat diabetes, hypertension, auto-immune disease and obesity BEFORE pregnancy occurs. This access will ensure our mothers are in the best shape possible to handle the physical demands of childbirth.
E- Education and Engagement: Educating our colleagues and ancillary staff in healthcare on the potential of implicit bias to cloud judgement and delay life-saving care. Taking the time to teach our patients ensuring understanding of the principles behind our testing, decision making and interventions. Engaging churches, civic organizations and non-OB physicians to partner with us in a way that fosters trust in the medical community
A- Advocacy: Encourage patients to have Advocates who ASK the important questions during their prenatal visits and support patients during and after birth. Encourage doula care.
M- Mentorship:Mentoring and increasing the number of midwives, doulas and physicians of color so that patients have access to more providers with like-minded and similar cultural perspectives.
We are committed to initiating efforts to work with state and national agencies, professional organizations and governing bodies to effect a change. We will remain visible and engaged as we continue our work delivering babies and attending to our mothers in the best way we know how."

redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Comparing WMI DateTime to String in Query I'm trying to query Win32_NTLogEvent for entries past the previous time that I ran the query. I've tried using a string variable so that I can change it every time I run the script. But I am getting a null returned for the generated collection. I've looked up what I can about WMI DateTimes and using them in comparisons. Although I have found some seemingly conflicting information (namely some sources using human readable to compare directly with UTC and others not). I've tried a UTC string and a human readable string. But neither seem to work. I'm thinking it is because I need to compare a datetime to a datetime as opposed to a string to a string. Although many sources seem to say that a string to a string would work in this case. But, even if I am right, I'm not sure how to convert the time for every object in Win32_NTLogEvent while inside the query.
Here is the relevant part of my script. The UTC that is commented out is just there because I don't want to retype the date if I have to go back to UTC:
strTimeMin = "01/01/1970/0:00:00"
'19700101000000.000000-480
Set objWMIService = GetObject("winmgmts:" _
 & "{impersonationLevel=impersonate}!\\" & strComputer & "\root\cimv2")

'Querying Event Logs

Set colLoggedEvents = objWMIService.ExecQuery _
 ("SELECT * FROM Win32_NTLogEvent WHERE Logfile = 'system' AND "_
 & "Type = 'Error' AND TimeGenerated > " & strTimeMin & "")

Thanks for any help!

A: UTC strings should work fine. However, since they're strings you need to put them between single quotes in your WMI query:
computer = "..."
minTime  = "20140801000000.000000-000"

Set wmi = GetObject("winmgmts:\\" & computer & "\root\cimv2")
qry = "SELECT * FROM Win32_NTLogEvent " & _
      "WHERE LogFile = 'System' AND Type = 'Error' " & _
      "AND TimeGenerated > '" & minTime & "'"
For Each evt In wmi.ExecQuery(qry)
  ...
Next

redpajama_set_name: RedPajamaStackExchange


text:
Flexible workspaces can unlock value for both your employees and your bottom line—regardless of your company size
Collaborative workspaces have been on the rise for the past decade—especially in the last year. In 2018, the scale of collaborative workspaces in Manhattan increased by nearly 70 percent, growing from 9.4 million square feet in 2017 to 13.5 million square feet, according to CBRE research. But it's not just a trend in New York. Flexible spaces are on the rise in cities around the world.
Why the sudden surge? Companies of all sizes are embracing collaborative workspaces—and for good reasons. Whether you're a solo entrepreneur working on launching your company or a longtime member of the Fortune 500, collaborative workspaces offer a wealth of benefits.
What is a collaborative workspace?
Collaborative workspaces are offices in which employees of various companies work under one roof. Companies sharing a collaborative workspace can come in all sizes—from growing startups to global enterprises. The space is usually comprised of a mix of private offices and shared common areas that allow employees flexibility throughout their workday.
One important fact to note: A collaborative space doesn't necessarily mean that your employees will be in a coworking area amid many other companies. In most cases, your company will have a dedicated office—or even several floors. But they'll still have the opportunity to access beautifully designed common areas and top-of-the-line amenities, which can unlock outsize value for your company.
The advantages of collaborative workspaces
Take a look at the business value collaborative workspaces can offer your employees and your bottom line—no matter your company size.
Agility to move at the speed of business
In today's fast-moving world, agility is a must. In order to move fast, your real estate must keep up with your business needs—whether that means opening an innovation lab for a moonshot project, setting up satellite offices in emerging markets, or sourcing a larger space for a successfully growing team. Collaborative workspaces give you that agility. They enable you to grow your business and the number of employees you hire without having to commit to inflexible leases in a more traditional building. With a collaborative space, you have the freedom to change the size of your team or even your location, without much effort or extra cost.
Easy move-in and fast setup
When you become a member of a collaborative workspace, there's no need to endure a stressful and expensive moving process. You don't need to purchase or bring desks or chairs. The Wi-Fi is fast, the printers are full of ink, and the phones are plugged in and ready to use. Signing on to use a collaborative space means that the operational tasks that would have required weeks of your team's efforts have already been resolved. You and your employees can just come in and get straight to work.
Office space in prime locations
Prime real estate is expensive and can be difficult to source. Yet in order to attract and retain talent, companies need their offices to be in neighborhoods that are centrally located near other businesses, transportation, shops, and restaurants. On top of that, the buildings themselves must be bright, clean, and modern.
Collaborative workspaces offer a way into more expensive and in-demand spaces in prime locations that may have been prohibitive if you were renting the space yourself. Most collaborative workspaces are located in financial centers or busy business districts in their respective cities. They offer you the ability to quickly open an office—no sourcing or costly build-outs required.
Cost-efficiency
In many cases, collaborative workspaces can help you cut costs by allowing you to pay for only what you need. For example, if you're setting up a new regional headquarters and have only 10 current employees there, renting a full-floor office would result in wasted space—and cost. By placing those employees in a private office in a collaborative workspace, you're still giving them a dedicated workplace, but only paying for the space they're using. Best of all, you can easily add space as the team grows.
Ability to scale with ease
No matter your company size, growth is a primary objective—and collaborative workspaces can help you scale. Building a team in a test market? Going on a hiring spree for a division that is key to your company's success? Opening several new locations around the world in one year? Placing teams in a collaborative workspace allows you to give them an inspiring place to work together immediately.
All-inclusive amenities
If you rent your own office, you have to pay for utilities, office supplies, and additional amenities—plus an office manager and support staff to oversee them. With a collaborative workspace, utilities like water, gas, electricity, and Wi-Fi are included. Most also supply other amenities like coffee and tea, kitchen supplies, printing, and mail services.
A community concierge
In a collaborative workspace, a team is on hand to help with anything you need. If you have questions about the space, technology, amenities, or neighborhood (like where's the best place for a business lunch), you can reach out to the community team, which acts as a dedicated concierge.
Tech-enabled workspace
Configuring the IT infrastructure in any office is a time-consuming and expensive endeavor, requiring the work of multiple teams and vendors. However, with a collaborative workspace, all the technology is included: high-speed, secure Wi-Fi; conference room videoconferencing; security badges for swiping into the space; electrical outlets where people can charge up.
Space designed so employees can do their best work
In the past several years, the workplace has become more human-centric. Rather than expecting people to come into an office and spend eight hours a day in a cubicle, companies are providing employees with spaces that suit their work styles. That's why many collaborative spaces have been designed for activity-based working: People can pop into phone booths to make private calls or tackle a project that requires focus. They can have informal meetings at café-style tables. For those who prefer to work in a more casual atmosphere, there are couches and other forms of soft seating. Giving employees the ability to choose when and where they work can result in higher productivity and improved work quality.
Even if your company has a private office or floor in a collaborative workspace, employees can still access the building's common areas. This gives them the opportunity to network with people from other companies, including entrepreneurs, freelancers, and remote workers. This flow of knowledge and creativity can be a major benefit. In fact, many global enterprises place teams in collaborative spaces so they can absorb new, innovative ideas from others who are not usually in their network.
A space that reflects your company culture
While a collaborative workspace has been intentionally designed so employees can do their best work, you still have the opportunity to make it your own. Depending on the size of your office, there are various ways to configure the space so it reflects your company. You can hang up your own artwork and bring in your own fixtures, like rugs and lamps. If you have a private floor, there are opportunities to incorporate your branding, logo, and company colors so the space feels uniquely yours.
Stronger employee ties to your company
Have you ever wondered whether your company culture would be diluted in a collaborative workspace? Workplace strategists have too, and they've looked into it. A team of researchers from the University of Michigan's Stephen M. Ross School of Business found that employees identified significantly more with their company's culture than that of a collaborative workspace. The study also found that working in a collaborative space improved employee perception of the company.
These are just a few benefits collaborative workspaces offer companies. As such, more companies are building flexible workspaces into their portfolios, and leveraging them to improve their business.
Five Office Furniture Trends
Collaboration & Mobility


Schedule your next trip. Nothing cheers you up more than looking ahead to your next vacation. Whether it's a family reunion in the Outer Banks or a voyage to the fantastic islands of Japan, planning a new venture will give everyone something to look forward to and get the enthusiasm flowing. And while you plan, don't forget to check out your We Florida Financial member discounts from Dream Vacations.
Declutter. Cleaning and decluttering is positive therapeutic. Clearing out old files at work will set the stage for new projects and possibilities. Clearing out old clothes and broken items at home will create space and breathing room. You can also bless others by giving away things you no longer need.
Sing and dance to happy music. Whether it's classical sounds, rap from Pitbull or the rhythms of the Wailers, blast the music when you are alone and go to your happy place. I do. Music reduces stress, lessens anxiety and helps with mental sharpness.
Start a gratitude journal. In a world where we are bombarded daily with negative news and contentious happenings, it helps to focus attention on the positive things in our lives by writing them down in a gratitude journal. The journal itself can be a regular notebook or a store bought dairy. Just the simple habit of reflecting on what we are grateful for can actually lead to a happier, more content life. I am trying it this year and encouraging my children and friends to do the same.
Start your financial plan for the new year. If the holiday bills are starting to come in and you realize you've overdone it, don't bury your head in the sand. Take a look at how much you've spent, divide it by 12 and start saving. If monthly budgeting is a problem, you can make this task easier with We Florida Financial's online banking budgeting tool. Anyone can do it.
So cheer up. Beat those blues and forge ahead to a spectacular and productive 2019!


My name is Chris Elam, and I work in the office of Fort Bend County Commissioner Andy Meyers. Our office is looking to fill two unpaid research internship positions and is reaching out to the local Katy home school community to solicit applications from interested high school students.
Interested applicants could start immediately or during the summer months. As a K-12 home school graduate myself (HCYA graduating class of 1997), I know what a great resource these types of internships can be for a high school student's resume. I'd certainly be appreciative of any help or further contact info you might have that could help me promote these internships in our local community through your network or others.
My phone contact information is at the bottom of the email. Feel free to contact me with any questions or follow-up. Thank you.
The office of County Commissioner Andy Meyers is looking to fill two unpaid research internship positions. Interested applicants could start immediately or during the summer months. Work to be performed at the Precinct 3 Commissioners Office at 22333 Grand Corner Drive, Suite 105, Katy, TX 77494, generally located at the northeast corner of FM 1093 Westpark Tollway and SH 99 Grand Parkway. Successful applicants under the age of 18 will be asked to provide a signed parental consent form.
Our research interns provide support on a variety of projects in support of communications and community interaction within the County Commissioner's office. We are interested in taking on 2 computer-literate high school students who are self-motivated and able to use several online sources of information to build databases and research local topics. You will gain experience with research, writing, and working independently and as part of a team – skills that may be attractive to a future or current employer. You will also be able to directly participate in the local governmental process and attend events such as: agenda briefings, commissioners court meetings, HOA leadership meetings, etc. Some familiarity with using Google Drive is recommended but not required.


Authorities said David Wright recruited for the Islamic State and plotted the death of blogger Pamela Geller, a controversial critic of Islam.
An Everett man was sentenced Tuesday to 28 years in federal prison for plotting to kill Americans on behalf of the Islamic State, a punishment that spared him life in custody.
David Daoud Wright, 28, will be in his early 50s by the time he is released from prison for plotting to behead an anti-Islam activist and urging his uncle to attack law enforcement officials in a Roslindale parking lot in 2015.
His uncle, Usaamah Rahim, was fatally shot by authorities after he advanced on them with a machete. Just hours earlier, Wright had urged him to assault officers and pursue martyrdom.
In Boston's federal courthouse on Tuesday, Wright tearfully apologized to his family, police, and Pamela Geller, the activist he, his uncle, and another man had plotted to kill in the name of ISIS.
US District Court Judge William G. Young told Wright he knowingly chose to take up the cause of terrorists.
During the four-week trial in October, Hedges argued that the 6-foot-7-inch Wright weighed more than 500 pounds in 2015, an unhappy man with no job prospects who deluded himself into thinking he was an ISIS combatant.
Wright testified that he never took his uncle seriously and was only role-playing as an escape from his bleak life.
On Tuesday, Young flatly rejected that claim.
Wright was convicted of conspiring to support a terrorist organization; conspiring to commit acts of terrorism beyond national boundaries; conspiracy to commit obstruction of justice; and two counts of obstruction of justice.
At trial, prosecutors said Wright knew his uncle was communicating with Junaid Hussain, a member of ISIS in Syria who provided Rahim information about Geller. Hussain was killed in August 2015 in an airstrike in Raqqah, Syria.
"He was committed to waging war against the United States," she said.
Young said that while Wright's actions merited a life sentence, he needed to consider sentences in other terrorist cases where the defendant had not directly committed a deadly act.
Young said he asked the jurors after delivering their verdict what they believed Wright should receive as a sentence. Their answers averaged out to 23 years.
"I'm having trouble with a life sentence for this," Young said. "If I look at the sentences of others . . . I see significant differences." In 2012, Tarek Mehanna, a 29-year-old Sudbury man, was sentenced to 17½ years for conspiring with Al Qaeda to commit murder. That same year, 27-year-old Rezwan Ferdaus was sentenced to 17 years in Boston federal court for plotting an attack on the Pentagon.
Attorneys Michael Tumposky (left) and Jessica Hedges (center) left the Moakley Courthouse after David Wright's sentencing.
Hedges pointed out that officers at the Plymouth County House of Correction, where Wright has been held in isolation since his 2015 arrest, had been impressed by his respectful, quiet behavior. In a lengthy letter to Young, Wright's mother described her son as an insecure man who was self-conscious about his enormous stature and never had a consistent father figure. The family fled Wright's father, who was abusive, when Wright was 2 years old, she wrote.
But Young said he was sentencing Wright based on his actions in 2015.
Pam Geller spoke outside the Moakley Courthouse after David Wright was sentenced.
Geller attended the hearing and read a statement urging a life sentence. She said her family has been traumatized by the threats against her life and that she has spent tens of thousands of dollars on security.


"Each peso [or dollar] is a contract between the government and the peso holder. That contract guarantees that each peso -- as a unit of value that the holder has worked hard to get -- will be worth as much tomorrow as today. If the government breaks the contract, it's breaking the law. The only role of government in the economy should be to guarantee the integrity of market transactions."
In our case,the "peso" is guaranteed to be worth less tomorrow than it is today. It's back to the first quote about inflation.
Awesome, except that is impossible for the government to gaurantee anything to do with the value of currency. The private and foreign owned Federal Reserve does all that as well as chooses your candidates for you. Democracy is a sham.
Caught in the cross-hairs of corrupt international banking practices. Slavery through socialism. Many have died bringing this point to matter. Let alone the exchange for coined money !
There are (depending on jurisdictional definition) 5 elements to a contract. One of which is knowledge of that which is being contracted. The knowledge here referenced to is similar in effect to a "social contract" - an oxymoron and impossible happenstance (not a contract). The stated scenario does not broach any of the 5 elements of a contract.
The entire concept alluded to is an exercise in "legal positivism" illusion. Natural law (fiscal law) supersedes the above word salad as government can not guarantee a measure of exchange between 2 private parties. All the comments above more accurately describe government's role in economics than the quote's.
"The only role of government in the economy should be to guarantee the integrity of market transactions."


Children's Healthcare of Atlanta is a not-for-profit organization dedicated to providing high-quality pediatric care to kids from all walks of life—but we can't do it alone.
On average, it costs $3.7 million a day to operate our three facilities. We depend on the generous support of donors to help uphold our mission to make kids better today and healthier tomorrow. Donor support allows us to purchase new equipment, provide top-notch clinical care, and offer patient services that make us uniquely Children's.
Young professionals in their 20s and 30s collaborate to host fundraising and social events throughout the year. We also participate in special service projects inside and outside our three hospitals, including volunteering with patients and families. We raise funds each year to fulfill several crucial patient and family needs, such as Family Support Services, Primary Care and Research. Get involved today by joining us at our next event!
Friends Junior Committee (FJC) is a 501(c)6 non-profit organization.