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Previously, we have successfully used noninvasive magnetic resonance (MR) and bioluminescence imaging to detect and monitor mPEG-poly(Ala) hydrogel-embedded MIN6 cells at the subcutaneous space for up to 64 days. In this study, we further explored the histological evolution of MIN6 cell grafts and correlated it with image findings. MIN6 cells were incubated overnight with chitosan-coated superparamagnetic iron oxide (CSPIO) and then 5 × 106 cells in the 100 μL hydrogel solution were injected subcutaneously into each nude mouse. Grafts were removed and examined the vascularization, cell growth and proliferation with anti-CD31, SMA, insulin and ki67 antibodies, respectively, at 8, 14, 21, 29 and 36 days after transplantation. All grafts were well-vascularized with prominent CD31 and SMA staining at all time points. Interestingly, insulin-positive cells and iron-positive cells were scattered in the graft at 8 and 14 days; while clusters of insulin-positive cells without iron-positive cells appeared in the grafts at 21 days and persisted thereafter, indicating neogrowth of MIN6 cells. Moreover, proliferating MIN6 cells with strong ki67 staining was observed in 21-, 29- and 36-day grafts. Our results indicate that the originally transplanted MIN6 cells proliferated from 21 days that presented distinctive bioluminescence and MR images. [ABSTRACT FROM AUTHOR]

Vascularized composite allotransplantation is an emerging strategy for the reconstruction of unique defects such as amputated limbs that cannot be repaired with autologous tissues. In order to ensure the function of transplanted limbs, the functional recovery of the anastomosed peripheral nerves must be confirmed. The immunosuppressive drug, tacrolimus, has been reported to promote nerve recovery in animal models. However, its repeated dosing comes with risks of systemic malignancies and opportunistic infections. Therefore, drug delivery approaches for locally sustained release can be designed to overcome this issue and reduce systemic complications. We developed a mixed thermosensitive hydrogel (poloxamer (PLX)-poly(l-alanine-lysine with Pluronic F-127) for the time-dependent sustained release of tacrolimus in our previous study. In this study, we demonstrated that the hydrogel drug degraded in a sustained manner and locally released tacrolimus in mice over one month without affecting the systemic immunity. The hydrogel drug significantly improved the functional recovery of injured sciatic nerves as assessed using five-toe spread and video gait analysis. Neuroregeneration was validated in hydrogel–drug-treated mice using axonal analysis. The hydrogel drug did not cause adverse effects in the mouse model during long-term follow-up. The local injection of encapsulated-tacrolimus mixed thermosensitive hydrogel accelerated peripheral nerve recovery without systemic adverse effects. [ABSTRACT FROM AUTHOR]

The oral route is the most popular way of drug administration because of good patient compliance and ease of use. However, the oral delivery of peptides and proteins is difficult, mainly due to poor oral bioavailability. In past decades, researchers have developed several strategies to improve oral bioavailability by avoiding losing activity in the gastrointestinal (GI) tract and enhancing the intestinal permeability of these drugs. Methoxy poly(ethylene glycol)-poly(l-alanine) (mPEG-PA) is a thermo-sensitive hydrogel exhibiting a sol-to-gel phase transition property. This characteristic is appropriate for encapsulating peptide or protein drugs. To enhance the adhesion ability to intestinal mucus, a thermo-sensitive polymer, mPEG-PA, modified with charged amino acid lysine was developed. This positively charged material would help to bind the negatively charged mucin in mucus. The synthesis was conducted by individually synthesizing mPEG-PA and poly(l-lysine) (PLL) of different lengths via ring-opening polymerization. Then, mPEG-PA and PLL were combined using an NHS ester reaction to synthesize the triblock copolymer (mPEG-PA-PLL). Biocompatibility and the release of calcitonin from the synthesized hydrogel particles under different pH were examined. The initial data showed that the newly design material had a promising potential for the oral delivery of peptide drugs. [ABSTRACT FROM AUTHOR]

We developed an injectable hydrogel system with a sustained release of TGF‐β3 through growth factor‐loaded microsphere to mimic the cartilage‐like microenvironment. Poly(lactic‐co‐glycolic acid) (PLGA) microspheres incorporated in three dimensional (3D) scaffolds were chosen because of its regulatory approval, good biodegradability, and acting as carriers with sustained release behavior. We evaluated sustained release of TGF‐β3 by PLGA microspheres encapsulated in methoxy poly(ethylene glycol)‐poly(alanine) (mPA) hydrogels and the resulting enhanced chondrogenic effects. We reported here the effect of the proposed system for sustained release of growth factors on chondrogenesis in cartilage regeneration. PLGA microspheres were used in our thermosensitive mPA hydrogel system with bovine serum albumin as a stabilizing and protecting agent for the emulsion and TGF‐β3 enabling sustained release. Gelation, structural properties, and in‐vitro release of this composite, that is, microspheres in hydrogel, system were investigated. Using PLGA microspheres to carry growth factors could complement the mPA hydrogel's ability to provide an excellent 3D microenvironment for the promotion of chondrogenic phenotype as compared the systems using mPA hydrogel or microspheres alone. Our study demonstrated that this synthesized composite hydrogel system is capable of modulating the biosynthetic and differentiation activities of chondrocytes. The sustained release of TGF‐β3 in this novel hydrogel system could improve biomedical applicability of mPEG‐polypeptide scaffolds. The distinctive local growth factor delivery system successfully combined the use of both polymers to be a suitable candidate for prolonged articular cartilage regeneration. [ABSTRACT FROM AUTHOR]

Certain amphiphilic polymers can self‐assemble to form various structures, such as micelles and hydrogels in aqueous medium, depending on the concentration or temperature. These different structures have found many applications in biomedical and material processing fields. The assembly processes of the polypeptide‐containing diblock copolymer, methoxy poly(ethylene glycol)‐block‐poly(L‐alanine) (mPEG‐PA), was studied to elucidate the relationship between different structures with parameters such as chain lengths (volume fraction) of the two blocks, molecular weights, medium polarity, temperature, and concentration. Gelation mechanism was especially focused in the study. Various solution‐cast morphologies observed by scanning electron microscopy (SEM) imaging including cylinders and micelles aggregates can be obtained by using solvents with different polarity for casting with simply tuning the chain lengths. The sol‐to‐gel transition mechanism can be best explained by phase separation between polymer‐rich and water‐rich phases. It might be spinodal decomposition process to cause the phase separation. Furthermore, the branch and flack structures can be observed due to phase separation mechanism and different chain lengths by SEM images. This result offers new insights into behavior of mPEG‐PA system, enabling more controlled manipulation to various applications. [ABSTRACT FROM AUTHOR]

Hydrogels are suitable biomaterials for cartilage tissue engineering due to the excellent ability to retain water to provide suitable environment for the tissue, however, the insufficient mechanical properties often prevent their wider applications. The objective of this study was to fabricate biocompatible hydrogels with good mechanical performance, high‐water content, and porous microstructure for cartilage regeneration. Photocrosslinked hydrogels are one of the most widely used systems in tissue engineering due to the superior mechanical properties. In this study, block copolymer, poly(ε ‐caprolactone)‐poly(ethylene)‐poly(ε‐caprolactone) diacrylate (PCL–PEG–PCL; PEC), was prepared by ring‐opening polymerization, and PEC hydrogels were made through free radical crosslinking mechanism. Agarose network is chosen as another component of the hydrogels, because of the high‐swelling behavior and cartilage‐like microstructure, which is helpful for chondrocytes growth. Interpenetrating networks (IPN) were fabricated by diffusing PEC into agarose network followed by photo‐crosslinking process. It was noted that incorporating PEC into the agarose network increased the elastic modulus and the compressive failure properties of individual component networks. In addition, high‐swelling ratio and uniform porosity microstructures were found in the IPN hydrogels. IPN and PEC showed low cytotoxicity and good biocompatibility in elution test method. The results suggest promising characteristics of IPN hydrogels as a potential biomaterial for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

To reduce phenolic pollutants in the environment, many countries have imposed firm restrictions on industrial wastewater discharge. In addition, the current industrial process of phenolic resin production uses phenol and formaldehyde as the reactants to perform a polycondensation reaction. Due to the toxicity of formaldehyde and phenolic pollutants, the main purpose of this research was to design a green process using horseradish peroxidase (HRP) enzymatic polymerization to remove phenols and to produce formaldehyde-free phenolic polymers. In this study, the optimal reaction conditions, such as reaction temperature, pH, initial phenol concentration and initial ratio of phenol, and H2O2, were examined. Then, the parameters of the enzyme kinetics were determined. To solve the restriction of enzyme inactivation, several nonionic surfactants were selected to improve the phenol removal efficiency, and the optimal operation conditions in a surfactant-containing system were also confirmed. Importantly, the molecular weight of the synthetic phenolic polymers could be controlled by adjusting the ratio of phenol and H2O2. The content of biphenols in the products was almost undetectable. Collectively, a green chemistry process was proposed in this study and would benefit the treatment of phenol-containing wastewater and the production of formaldehyde-free phenolic resin in the future. [ABSTRACT FROM AUTHOR]

Subcutaneous islet transplantation can be easily conducted with minimum invasiveness, and the implant can be monitored easily. However, a major disadvantage of this transplantation technique is its poor efficacy which could be attributed to poor oxygenation and inadequate vascularization at the subcutaneous tissue. In this study, we explored the use of thermosensitive methoxy-poly(ethylene glycol)-poly(Ala), mPEG-poly(Ala) hydrogels as cell-encapsulating materials for the subcutaneous transplantation of MIN6 cells. We confirmed favorable biocompatibility between the materials and cells in vitro, including cell viability and insulin secretion. Histopathological tissue analysis revealed that transplanted MIN6 cells survived and contained insulin in nude mice 14 days after implantation. Moreover, we observed positive CD31 staining, implying new vessel formation, in the graft without MIN6 cells at 7 and 14 days after implantation. These results indicate the feasibility of using mPEG-poly(Ala) hydrogels as delivery carriers for subcutaneous transplantation of MIN6 cells. [ABSTRACT FROM AUTHOR]

The general concept of tissue engineering is to restore biological function by replacing defective tissues with implantable, biocompatible, and easily handleable cell-laden scaffolds. In this study, osteoinductive and osteoconductive super paramagnetic Fe3O4 nanoparticles (MNP) and hydroxyapatite (HAP) nanoparticles were incorporated into a di-block copolymer based thermo-responsive hydrogel, methoxy(polyethylene glycol)-polyalanine (mPA), at various concentrations to afford composite, injectable hydrogels. Incorporating nanoparticles into the thermo-responsive hydrogel increased the complex viscosity and decreased the gelation temperature of the starting hydrogel. Functionally, the integration of inorganic nanoparticles modulated bio-markers of bone differentiation and enhanced bone mineralization. Moreover, this study adopted the emerging method of using either a supplementary static magnetic field (SMF) or a moving magnetic field to elicit biological response. These results demonstrate that combining external (magnet) and internal (scaffold) magnetisms is a promising approach for bone regeneration. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels are attractive alternative scaffolding materials for minimally invasive surgery through a simple injection and in situ gelling. In this study, a novel poly(ester-amide) polymer, methoxy poly(ethylene glycol)-poly(pyrrolidone-co-lactide) (mPDLA, P3L7) diblock copolymer, was synthesized and characterized for cartilage tissue engineering. A series of amphiphilic diblock copolymers was synthesized by ring-opening polymerization of mPEG 550, D,L-lactide, and 2-pyrrolidone. By dynamic light scattering analysis and tube-flipped-upside-down method, viscoelastic properties of the mPDLA diblock copolymer solution exhibited sol-gel transition behavior as a function of temperature. An in vitro degradation assay showed that degradation acidity was effectively reduced by introducing the 2-pyrrolidone monomer into the polyester hydrogel. Besides, mPDLA exhibited great biocompatibility in vitro for cell encapsulation due to a high swelling ratio. Moreover, cell viability and biochemical analysis proved that the mPDLA hydrogel presented a great chondrogenic response. Taken together, these results demonstrate that mPDLA hydrogels are promising injectable scaffolds potentially applicable to cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Climate change is directly linked to the rapid depletion of our non-renewable fossil resources and has posed concerns on sustainability. Thus, imploring the need for us to shift from our fossil based economy to a sustainable bioeconomy centered on biomass utilization. The efficient bioconversion of lignocellulosic biomass (an ideal feedstock) to a platform chemical, such as bioethanol, can be achieved via the consolidated bioprocessing technology, termed yeast surface engineering, to produce yeasts that are capable of this feat. This approach has various strategies that involve the display of enzymes on the surface of yeast to degrade the lignocellulosic biomass, then metabolically convert the degraded sugars directly into ethanol, thus elevating the status of yeast from an immobilization material to a whole-cell biocatalyst. The performance of the engineered strains developed from these strategies are presented, visualized, and compared in this article to highlight the role of this technology in moving forward to our quest against climate change. Furthermore, the qualitative assessment synthesized in this work can serve as a reference material on addressing the areas of improvement of the field and on assessing the capability and potential of the different yeast surface display strategies on the efficient degradation, utilization, and ethanol production from lignocellulosic biomass. [ABSTRACT FROM AUTHOR]

For this study, we cultured chondrocyte pellets in Dulbecco's modified Eagle's medium plus a 2 % fetal bovine serum medium, and treated them with 2- to 8-mer oligosaccharides of chondroitin sulfate A to examine the effects of these oligosaccharides on the differentiation and protection of chondrocytes. We found low-molecular-weight CSAs to increase the ratio of the gene expression levels of collagen II/collagen I of chondrocytes from the first day up to 14 days after culture compared with those under a CSA-free medium. Moreover, low-molecular-weight CSAs inhibited the expression of matrix metalloproteinases and peptidases, and stimulated an endogenous tissue inhibitor of metalloproteinases. The dp-8 (8-mer) CSA yielded the most effective response among promoting collagen type II protein secretions compared with other groups. [ABSTRACT FROM AUTHOR]

Curcumin is a naturally occurring compound that has been shown to have anti-oxidant, anti-inflammatory, and anti-carcinogenic activities. However, its pharmaceutical potential has been limited due to its low solubility in water. The use of amphiphilic nanocarriers is an attractive and simple method to solubilize curcumin. In this study, we modified Pluronic F-127 [poly(ethylene glycol)100-block-poly(propylene glycol)65-block-poly(ethylene glycol)100] (PF-127) with oligomers of alanine, an amino acid, to increase the drug entrapment efficiency of curcumin through core stabilization. Alanine-modified PF-127 exhibited lower critical micelle concentration and decreased molecular motion in both the hydrophilic and hydrophobic segments (1H NMR). Nanocarriers in the size range of 54.2–68.4?nm were observed. Entrapment efficiency of curcumin increased by at most 66% (from 25.3 to 91.3%) and the difference in solubility was clearly visualized by increased transparency of the nanocarrier solutions. Curcumin was released continuously up to 120?h from modified carriers, while drug release from unmodified carriers plateaued within 24?h. These modified nanocarriers exhibited no cytotoxicity and more efficiently delivered drugs to HeLa cells as confirmed by fluorescent microscopy. This study demonstrated that alanine modification of FDA-approved PF-127 affects copolymer nanoassembly and has a profound impact on curcumin loading and possibly on other hydrophobic drugs as well. [ABSTRACT FROM AUTHOR]

Temperature-sensitive hydrogels are attractive alternatives to porous cell-seeded scaffolds and is minimally invasive through simple injection and in situ gelling. In this study, we compared the performance of two types of temperature-sensitive hydrogels on chondrocytes encapsulation for the use of tissue engineering of cartilage. The two hydrogels are composed of methoxy poly(ethylene glycol)- poly(lactic- co-valerolactone) (mPEG-PVLA), and methoxy poly(ethylene glycol)-poly(lactic- co-glycolide) (mPEG-PLGA). Osmolarity and pH were optimized through the manipulation of polymer concentration and dispersion medium. Chondrocytes proliferation in mPEG-PVLA hydrogels was observed as well as accumulation of GAGs and collagen. On the other hand, chondrocytes encapsulated in mPEG-PLGA hydrogels showed low viability and chondrogenesis. Also, mPEG-PVLA hydrogel, which is more hydrophobic, retained physical integrity after 14 days while mPEG-PLGA hydrogel underwent full degradation due to faster hydrolysis rate and more pronounced acidic self-catalyzed degradation. The mPEG-PVLA hydrogel can be furthered tuned by manipulation of molecular weights to obtain hydrogels with different swelling and degradation characteristics, which may be useful as producing a selection of hydrogels compatible with different cell types. Taken together, these results demonstrate that mPEG-PVLA hydrogels are promising to serve as three-dimensional cell carriers for chondrocytes and potentially applicable in cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3311-3319, 2013. [ABSTRACT FROM AUTHOR]

The clinical demand for cartilage tissue engineering is potentially large for reconstruction defects resulting from congenital deformities or degenerative disease due to limited donor sites for autologous tissue and donor site morbidities. Cartilage tissue engineering has been successfully applied to the medical field: a scaffold pre-cultured with chondrocytes was used prior to implantation in an animal model. We have developed a surgical approach in which tissues are engineered by implantation with a vascular pedicle as an in vivo bioreactor in bone and adipose tissue engineering. Collagen type II, chitosan, poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were four commonly applied scaffolds in cartilage tissue engineering. To expand the application of the same animal model in cartilage tissue engineering, these four scaffolds were selected and compared for their ability to generate cartilage with chondrocytes in the same model with an in vivo bioreactor. Gene expression and immunohistochemistry staining methods were used to evaluate the chondrogenesis and osteogenesis of specimens. The result showed that the PLGA and PCL scaffolds exhibited better chondrogenesis than chitosan and type II collagen in the in vivo bioreactor. Among these four scaffolds, the PCL scaffold presented the most significant result of chondrogenesis embedded around the vascular pedicle in the long-term culture incubation phase. [ABSTRACT FROM AUTHOR]

The acinus-mimicking microfluidic chip, which simulates the in vivo condition of the liver, was developed and reported in this paper. The gradient microenvironment of the liver acinus is replicated within this proposed microfluidic chip. The advantage of this acinus-mimicking chip is capable of adjusting the concentration gradient in a relatively short period of time at around 10 s. At the same instance the non-linear concentration gradient can be presented in the various zones within this microfluidic chip. The other advantage of this proposed design is in the convenience of allowing the direct injection of the cells into the chip. The environment within the chip is multi-welled and gel-free with high cell density. The multi-row pillar microstructure located at the entrance of the top and bottom flow channels is designed to be able to balance the pressure of the perfusion medium. Through this mechanism the shear stress experienced by the cultured cells can be minimized to reduce the potential damage flow from the perfusion process. (3)The fluorescence staining and the observations of the cell morphology verify the life and death of the cells. The shear stress experienced by the cells in the various zones within the chip can be effectively mapped. The serum glutamic oxaloacetic transaminase (SGOT) collected from the supernatants was used to determine the effects of the degassing process and the shear stress of the medium flow on the cultured cells. [ABSTRACT FROM AUTHOR]

The long term in vivo biocompatibility is an essential feature for the design and development of sustained drug release carriers. In the recent intraocular drug delivery studies, hydrogels were suggested as sustained release carriers. The biocompatibility test for these hydrogels, however, was commonly performed only through in vitro cell culture examination, which is insufficient before the clinical applications. We compared three thermosensitive hydrogels that have been suggested as the carriers for drugs by their gel-solution phase-change properties. A new block terpolymer (PEOz-PCL-PEOz, ECE) and two commercial products (Matrigel® and Pluronic F127) were studied. The results demonstrated that the ocular media remained translucent for ECE and Pluronic F127 in the first 2 weeks, but cataract formation for Matrigel occurred in 2 weeks and for Pluronic F127 in 1 month, while turbid media was observed for both Matrigel and Pluronic F127 in 2 months. The electrophysiology examinations showed significant neuroretinal toxicity of Matrigel and Pluronic F127 but good biocompatibility of ECE. The neuroretinal toxicity of Matrigel and Pluronic F127 and superior biocompatibility of ECE hydrogel suggests ECE as more appropriate biomaterial for use in research and potentially in intraocular application. [ABSTRACT FROM AUTHOR]

To further enhance the performance of biodegradable polymer-based medical devices, there is an increasing need to obtain independent control of key properties such as mechanical strength, degradation rate, and bioactivity. In this study, biodegradable copolymers of poly(1,6-bis- p-carboxyphenoxyhexane- co-sebacic anhydride) (CPH:SA) are synthesized, via melt condensation techniques, at three different molar ratios (7 : 3, 5 : 5, and 3 : 7). Tablets of the copolymers are prepared by mold casting at high temperature. Using an in vitro degradation test, copolymer tablets demonstrate a suitable mechanical strength, a slight decrease in pH value, and a slow degradation rate. High cell viability is observed on the surface of the copolymer tablets. The 3-(4,5dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and live/dead staining demonstrate reduced toxicity and high cell survival. In vitro testing with C2C12 cells reveals good cellular attachment and spreading on the tablet surfaces, with the best properties displayed by the 7 : 3 molar ratio copolymer. Materials composed of CPH:SA have the potential to serve as medical implants. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 [ABSTRACT FROM AUTHOR]

Materials that can respond to multiple stimuli, such as temperature and pH changes, are of considerable interest for applications in drug delivery systems. Notably, α,β-[poly(2-hydroxyethyl)- DL-aspartamide] is a potentially useful material for such applications. This study investigated the temperature and pH responsiveness of polymers structurally similar to α,β-[poly(2-hydroxyethyl)- DL-aspartamide], namely, poly(α,β- N-substituted- DL-aspartamide)s, in aqueous media. These polymers were derived from polysuccinimide (PSI), which was first synthesized via acid-catalyzed bulk polycondensation of L-aspartic acid (L-ASP) in the presence of 85% o-phosphoric acid under N2. Two primary amino alcohols, 4-aminobutanol (4AB) and 6-aminohexanol (6AH), were then respectively utilized to modify PSI to form poly (α,β- N-substituted- DL-aspartamide)s via aminolysis. Different ratios of these two amino alcohols were used to modify the polymer to produce a series of copolymers with lower critical solution temperatures ranging from 53-28°C when dispersed in aqueous media. Moreover, the properties of the poly(α,β- N- substituted- DL-aspartamide)s in aqueous solution were affected by pH changes. The morphology of the particles formed by these amphiphilic polymers was observed using scanning electronic microscopy and transmission electronic microscopy, and the particles were found to be polymersomes with shell and hollow core structures and diameters of 0.5-1 μm. Other properties of this series of self-assembly copolymers were also characterized. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

This study designed a series of polyanionic nanocarriers based on biodegradable and biocompatible poly (aspartic acid)s for oral administration. First, polysuccinimide (PSI) was synthesized from L-aspartic acid using acid-catalyzed bulk thermal polycondensation and acid-catalyzed thermal polycondensation in a mixture of mesitylene/sulfolane. PSI-C was then synthesized by aminolysis with nucleophile, hexadecylamine to react with PSI known as nucleophilic addition. Finally, a series of partially esterified poly (aspartic acid)s was produced by alkaline treatment to afford an amphiphilic polyanion, poly (sodium aspartate- g-hexadecyl aspartate) (Na-PASP- g-C-PASP). HNMR, FTIR, DSC and GPC were utilized to demonstrate and characterize the polymers. The synthesized polyanion could be self-assembled into the nano-scaled micelles and be independent of pH in phosphoric buffer solutions. The hydrodynamic diameter and zeta potential were measured using the dynamic light scattering (DLS) method, and the critical micelle concentration (CMC) was determined using the fluorescence spectrophotometer. The micellar morphologies were examined using transmission electron microscopy (TEM), and atomic force microscopy (AFM) to present the nano-dimensional sphere. The stability of size transition at different pH levels, from strong acid to alkaline, proved that the micelles could stably transport from the stomach to intestinal lumen prior to arriving in the epithelium of the small intestine. [ABSTRACT FROM AUTHOR]

Suitable carrier systems for sustained release of curcumin were studied by using the self-assembled polymeric micelles. Poly(ethylene glycol) methyl ether and poly(aromatic anhydride) were used as the hydrophilic and hydrophobic blocks, respectively, in forming amphiphilic diblock copolymers. Four different types of polymers methoxy poly(ethylene glycol- b-1,3-bis( p-carboxyphenoxy)propane) (mPEG [ABSTRACT FROM AUTHOR]

In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte-keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds. [ABSTRACT FROM AUTHOR]

Polyanhydrides have been used in many drug delivery systems because of their biodegradability and biocompatibility. Their degradation pattern of surface erosion made them suitable for stable drug release applications. However, in nanoparticle systems, this degradation pattern may not hold, and the drug release kinetics will be different also. In this study, copolymers of 1,3‐bis(p‐carboxyphenoxy)propane (CPP) and sebacic acid (SA) were synthesized to investigate the different degradation patterns of disk and nanoparticle forms of polyanhydride, in addition to the study of the method of preparation of nanoparticles from these copolymers. By using oil‐in‐water emulsion and poly(vinyl alcohol) (PVA) as emulsifier, nanoparticles of the size 200–500 nm were prepared. The size of the particles can be controlled by varying polymer concentration or PVA concentration, but different SA:CPP ratio did not affect the particle size significantly. Degradation was followed by detecting the amount of monomers released to the medium. It was found that CPP and SA were released at approximately the same rate from nanoparticles; while in disk form, SA was released much faster than CPP. It was found that contrary to general trend in disks, higher CPP content, a more hydrophobic component than SA, in the copolymer actually accelerated the degradation of nanoparticles. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [ABSTRACT FROM AUTHOR]

Surfactin productivity by Bacillus subtilis was increased from 0.33 g l-1 to 2.6 g l-1 by adding 0.01 mM Mn2+ to a defined glucose medium. The final yield exceeded that of most reported values for genetically improved strains. [ABSTRACT FROM AUTHOR]

Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The accumulation of beta-2-microglobulin (β2M) in collagen-rich tissues has been proven to be the main cause of dialysis related amyloidosis. However, it remains uncertain which technique for the removal of β2M can be used without compromising the advantages of other dialysis strategies. A new concept, an immunoadsorption wall, which combines the principles of immunoisolation and immunoadsorption is proposed to remove β2M. The present investigations suggested that the application of the concept to clinical use is feasible and worthwhile. The concept, if validated, will help shape a novel multitask type of artificial kidney based on the combination of different separation technologies. [ABSTRACT FROM AUTHOR]

In the fermentation of Escherichia coli, a ceramic membrane filter was used in conjunction with a fermenter for cell-recycle operation. The metabolic behaviour, especially the acetic acid production and the specific growth rate, under different concentrations of dissolved O was investigated. An unstructured model was constructed, and it was shown that the observed lower cell density under low dissolved O concentrations was accompanied by large acetic aicd production. However, the concentration of acetic acid was not high enough to cause the observed growth inhibition, and inhibition by other metabolites under low O environment is suspected. [ABSTRACT FROM AUTHOR]

A new methylotrophic strain (T15), which employs the ribulose monophosphate (RuMP) cycle of formaldehyde assimilation, was isolated on the basis of high in vitro activities of formaldehyde and formate dehydrogenases (19 and 678 mU per mg protein, respectively). Serial subculturing of the strain in batch cultures, on 4 g/l CHOH for 6 months, led to loss of substantial percentages of the NAD-linked formaldehyde (25%) and formate (98%) dehydrogenases. The activities of these two enzymes were partially recovered when cells were grown continuously at very low dilution rate (0.03 h). We found large variations (40 to 1000%) in the activities of other key enzymes of carbon-substrate oxidation (both linear and cyclic) and assimilation, in batch cultures with pure and mixed substrates, and in continuous cultures of different dilution rates. Key intracellular reaction rates, including those of the cyclic and linear substrate oxidation, were measured in vivo using a C-tracer technique in both continuous and batch cultures. The results indicate significant variations in these reaction rates, particularly those of linear and cyclic carbon oxidation. Overall, the cyclic oxidation appears to be employed to a larger (although not predominant) extent in strain T15 compared with another RuMP strain (L3) we have previously examined. T15 exhibits high biomass yields (up to 0.63 g cells per g CHOH) and growth rates (up to 0.46 h) on CHOH in batch cultures. CHNH can also be utilized as a substrate. In continuous culture, T15 could be grown at dilution rates up to 0.36 h with a corresponding biomass yield of 0.4. Examination of a large number of data on the biomass yields of strains T15 and L3 reveals that the large variations in yields derive from the variable branching of carbon flow between linear and cyclic oxidation and assimilation, rather than changes in the biosynthetic efficiency of carbon incorporation into biomass. [ABSTRACT FROM AUTHOR]

Formate transport and the effect of formate on growth and the membrane protonmotive force were studied in two ribulose-monophosphate-type obligate methylotrophs (bacterial strains T15 and L3). Formate was accumulated very fast by the membrane ΔpH according to the general transport mechanism of short-chain organic acids. Formate accumulation was reduced or abolished by a number of factors (protonophores, high extracellular pH, cell-starvation conditions) that reduced or abolished the ΔpH. Formate transport was accompanied by removal of protons from the medium by the cells. Since protons are released by the cells upon substrate oxidation, the stoichiometry of proton uptake upon formate transport could not be directly determined, although data suggest that formate is cotransported with one proton. The net rate of proton removal from the medium by the cells due to formate transport and oxidation increased with increasing formate concentrations or decreasing medium-pH values. The membrane protonmotive force of strain T15 was also studied as a function of the pH. High formate concentrations (of 100 to 400 mM) reduced the membrane ΔpH by ca. 20 to 60% and the growth rate by ca. 20 to 100% for both strains but to a different extent. For example, 400 mM formate inhibited growth by ca. 60% in strain T15 and by 100% in strain L3. The nature of growth inhibition by formate is discussed in some detail. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated the feasibility of subcutaneous transplantation of MIN6 cells embedded in a scaffold with poly(ethylene glycol) methyl ether (mPEG)-poly(Ala) hydrogels. In this study, we further tracked these grafts using magnetic resonance (MR) and bioluminescence imaging. After being incubated overnight with chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles and then mixed with mPEG-poly(Ala) hydrogels, MIN6 cells appeared as dark spots on MR scans. For in vivo experiments, we transfected MIN6 cells with luciferase and/or incubated them overnight with CSPIO overnight; 5 × 106 MIN6 cells embedded in mPEG-poly(Ala) hydrogels were transplanted into the subcutaneous space of each nude mouse. The graft of CSPIO-labeled MIN6 cells was visualized as a distinct hypointense area on MR images located at the implantation site before day 21. However, this area became hyperintense on MR scans for up to 64 days. In addition, positive bioluminescence images were also observed for up to 64 days after transplantation. The histology of removed grafts showed positive insulin and iron staining. These results indicate mPEG-poly(Ala) is a suitable scaffold for β-cell encapsulation and transplantation. Moreover, MR and bioluminescence imaging are useful noninvasive tools for detecting and monitoring mPEG-poly(Ala) hydrogel-embedded MIN6 cells at a subcutaneous site. [ABSTRACT FROM AUTHOR]

While perfluoroalkyl acids (PFAAs), also known as C8s, are used extensively in textile repellent coatings, concerns have arisen for their carcinogenicity and hazardous effects on the environment. In this study, a novel water‐based, nonfluoro, and nanobrush textile repelling agent was prepared by conventional sol–gel chemistry using amorphous fumed silica and n‐octyltriethoxysilane as the starting materials. Minimal interaction between the designed repelling agent and marketed water‐based resins was confirmed using linear viscosity region (LVR) analysis and asymmetric‐flow field‐flow fractionation (AF4), suggesting the self‐stratification potential of the repelling agent. More specifically, the repelling agent exhibited excellent compatibility and self‐stratifying ability with a force‐emulsified acrylic‐based resin, affording a water contact angle of 104.3° when incorporated at 7% solid content. Performance tests carried out on thermoplastic polyurethane (TPU) revealed excellent adhesion (100/100) of a final formulation, and a significant increase in water contact angle from 80.1° to 103.8° after treatment. In addition, the fouling area after the removal of a submerged sample from a mixture of slurry, polymer, and oil decreased from 48 to 1% when the repelling agent was added. Moreover, the sludge‐fouling property remained unchanged after 1000 cycles of abrasion. These findings demonstrate the potential of the described nonfluoro, nanobrush repelling agent as an environmentally safe alternative for use with commercial resins, in turn realizing a fully water‐based hydrophobic coating. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48003. [ABSTRACT FROM AUTHOR]

Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P–Lys–Ala–PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy. [ABSTRACT FROM AUTHOR]