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Non-destructive monitoring of engineered tissues is needed for translation of these products from the lab to the clinic. In this study, non-invasive, high resolution spectral ultrasound imaging (SUSI) was used to monitor the differentiation of MC3T3 pre-osteoblasts seeded within collagen hydrogels. SUSI was used to measure the diameter, concentration and acoustic attenuation of scatterers within such constructs cultured in either control or osteogenic medium over 21 days. Conventional biochemical assays were used on parallel samples to determine DNA content and calcium deposition. Construct volume and morphology were accurately imaged using ultrasound. Cell diameter was estimated to be approximately 12.5–15.5 µm using SUSI, which corresponded well to measurements of fluorescently stained cells. The total number of cells per construct assessed by quantitation of DNA content decreased from 5.6±2.4×104 at day 1 to 0.9±0.2×104 at day 21. SUSI estimation of the equivalent number of acoustic scatters showed a similar decreasing trend, except at day 21 in the osteogenic samples, which showed a marked increase in both scatterer number and acoustic impedance, suggestive of mineral deposition by the differentiating MC3T3 cells. Estimation of calcium content by SUSI was 41.7±11.4 µg/ml, which agreed well with the biochemical measurement of 38.7±16.7 µg/ml. Color coded maps of parameter values were overlaid on B-mode images to show spatiotemporal changes in cell diameter and calcium deposition. This study demonstrates the use of non-destructive ultrasound imaging to provide quantitative information on the number and differentiated state of cells embedded within 3D engineered constructs, and therefore presents a valuable tool for longitudinal monitoring of engineered tissue development. [ABSTRACT FROM AUTHOR]

There is increasing demand for reconstruction of glottal insufficiency. Several injection materials have been examined for this purpose, but all had limitations, such as poor long-term durability, migration from the injection site, inflammation, granuloma formation, and interference with vocal fold vibration due to viscoelastic mismatch. Here, we developed a novel injection material, consisting of polycaprolactone (PCL) microspheres, which exhibits better viscoelasticity than conventional materials, and Pluronic F127 carrier, which decreases the migration of the injection materials. The material was injected into rabbits with glottal insufficiency and compared with the FDA-approved injection material, calcium hydroxylapatite (CaHA). Endoscopic and histological examinations indicated that PCL/Pluronic F127 remained at the injection site with no inflammatory response or granuloma formation, whereas CaHA leaked out and migrated from the injection site. Therefore, vocal fold augmentation was almost completely retained during the 12-month follow-up period in this study. Moreover, induced phonation and high-speed recording of vocal fold vibration showed decreased vocal fold gap area in the PCL/Pluronic F127 group. Our newly developed injection material, PCL/Pluronic F127, permits efficient augmentation of paralyzed vocal fold without complications, a concept that can be applied clinically, as demonstrated by the successful long-term follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Temperature has been extensively explored as a trigger to control the delivery of a payload from environment-sensitive polymers. The need for an external heat source only allows limited spatiotemporal control over the delivery process. We propose a new approach by using the dissipative properties of a hydrogel matrix as an internal heat source when the material is mechanically loaded. The system is comprised of a highly dissipative hydrogel matrix and thermo-sensitive nanoparticles that shrink upon an increase in temperature. Exposing the hydrogel to a cyclic mechanical loading for a period of 5 min leads to an increase of temperature of the nanoparticles. The concomitant decrease in the volume of the nanoparticles increases the permeability of the hydrogel network facilitating the release of its payload. As a proof-of-concept, we showed that the payload of the hydrogel is released after 5–8 min following the initiation of the mechanical loading. This delivery method would be particularly suited for the release of growth factor as it has been shown that cell receptor to growth factor is activated 5–20 min following a mechanical loading. [Copyright &y& Elsevier]

Highlights: [•] We used graphene oxide as a drug-binding effector for cancer therapy drug loading and release. [•] The possible mechanism of the gelation of graphene oxide and polysaccharide was discussed. [•] Graphene oxide composite hydrogels showed excellent pH sensitive. [•] The KGM/SA/GO-3 hydrogels could control the drug release well. [Copyright &y& Elsevier]

Abstract: Chemically crosslinked hyaluronic acid hydrogels are synthesized with a homogeneous crosslinking process using divinyl sulfone (DVS) as crosslinking agent. Testing different conditions, in terms of both DVS content and curing time, we aim to keep control over the crosslinking process in order to prepare biocompatible hydrogels with mechanical properties closely approximating those of extracellular matrix (ECM) of natural stem cells niches (0.1÷50kPa). The hydrogels properties are evaluated through a reliable methodology based on three independent techniques: dynamic rheological analysis, used as benchmark method; swelling experiments following the Flory–Rehner theory and atomic force microscope (AFM) nanoindentation experiments. Our results demonstrate that controlling crosslinking parameters it is possible to design hydrogels with desired elastic moduli values. HA hydrogels can be ideal coating materials to be implemented in regenerative medicine and particularly in the engineering of ECM niches in vitro. [Copyright &y& Elsevier]

Abstract: Four-arm polyethylene glycol (PEG) cross-linked hyaluronic acid (HA) hydrogels containing PEGylated tumor necrosis factor-related apoptosis-inducing ligand (PEG-TRAIL) were fabricated, and their antitumor effects were evaluated in pancreatic cell (Mia Paca-2)-xenografted mice. HA was conjugated with 4-arm PEG10k-amine (a cross-linker) at ratios of 100:1 and 100:2 using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride as a cross-linker, and TRAIL or PEG-TRAIL was incorporated into these HA hydrogels. HA hydrogels at a 100:1 ratio were prepared in good yields (>88%), were moderately stiff, and gradually released PEG-TRAIL over ∼14days in vitro and over ∼7days in vivo (as determined by high-pressure liquid chromatography and infrared imaging). The released PEG-TRAIL was found to have obvious apoptotic activity in Mia Paca-2 cells. PEG-TRAIL HA hydrogels displayed remarkably more antitumor efficacy than TRAIL HA hydrogels in Mia Paca-2 cell-xenografted mice in terms of tumor volumes (size) and weights (453.2mm3 and 1.03g vs. 867.5mm3 and 1.86g). Furthermore, this improved antitumor efficacy was found to be due to the apoptotic activity of PEG-TRAIL in vivo (determined by a TUNEL assay) despite its substantially lower cytotoxicity than native TRAIL (IC50 values: 71.8 and 202.5ngml−1, respectively). This overall enhanced antitumor effect of PEG-TRAIL HA hydrogels appeared to be due to the increased stability of PEGylated TRAIL in HA hydrogels. These findings indicate that this HA hydrogel system combined with PEG-TRAIL should be considered a potential candidate for the treatment of pancreatic cancer. [Copyright &y& Elsevier]

Abstract: Phenol derivative-containing adhesive hydrogels has been widely recognized as having potential for biomedical applications, but their conventional production methods, utilizing a moderate/strong base, alkaline buffers, the addition of oxidizing agents or the use of enzymes, require alternative approaches to improve their biocompatibility. In this study, we report a polymeric, enzyme-mimetic biocatalyst, hematin-grafted chitosan (chitosan-g-hem), which results in effective gelation without the use of alkaline buffers or enzymes. Furthermore, gelation occurs under mild physiological conditions. Chitosan-g-hem biocatalyst (0.01%, w/v) has excellent catalytic properties, forming chitosan–catechol hydrogels rapidly (within 5min). In vivo adhesive force measurement demonstrated that the hydrogel formed by the chitosan-g-hem activity showed an increase in adhesion force (33.6±5.9kPa) compared with the same hydrogel formed by pH-induced catechol oxidation (20.6±5.5kPa) in mouse subcutaneous tissue. Using the chitosan-g-hem biocatalyst, other catechol-functionalized polymers (hyaluronic acid–catechol and poly(vinyl alcohol)–catechol) also formed hydrogels, indicating that chitosan-g-hem can be used as a general polymeric catalyst for preparing catechol-containing hydrogels. [Copyright &y& Elsevier]

Abstract: We report here a synthetically simple yet highly tunable and diverse visible light mediated thiol-vinyl gelation system for fabricating cell-instructive hydrogels. Gelation was achieved via a mixed-mode step-and-chain-growth photopolymerization using functionalized 4-arm poly(ethylene glycol) as backbone macromer, eosin-Y as photosensitizer, and di-thiol containing molecule as dual purpose co-initiator/cross-linker. N-vinylpyrrolidone (NVP) was used to accelerate gelation kinetics and to adjust the stiffness of the hydrogels. Visible light (wavelength: 400–700nm) was used to initiate rapid gelation (gel points: ∼20s) that reached completion within a few minutes. The major differences between current thiol-vinyl gelation and prior visible light mediated photopolymerization are that: (1) the co-initiator triethanolamine (TEA) used in the previous systems was replaced with multifunctional thiols and (2) mixed-mode polymerized gels contain less network heterogeneity. The gelation kinetics and gel properties at the same PEG macromer concentration could be tuned by changing the identity of vinyl groups and di-thiol cross-linkers, as well as concentration of cross-linker and NVP. Specifically, acrylate-modified PEG afforded the fastest gelation rate, followed by acrylamide and methacrylate-functionalized PEG. Increasing NVP concentration also accelerated gelation and led to a higher network cross-linking density. Further, increasing di-thiol peptide concentration in the gel formulation increased hydrogel swelling and decreased gel stiffness. Due to the formation of thiol-ether-ester bonds following thiol-acrylate reaction, the gels degraded hydrolytically following a pseudo first order degradation kinetics. Degradation rate was controlled by adjusting thiol or NVP content in the polymer precursor solution. The cytocompatibility and utility of this hydrogel system were evaluated using in situ encapsulation of human mesenchymal stem cells (hMSC). Encapsulated hMSCs remained alive (>90%) throughout the duration of the study and the cells were differentiated down osteogenic lineage with varying degrees by controlling the rate and mode of gel degradation. [Copyright &y& Elsevier]

Abstract: Future ophthalmic therapeutics will require the sustained delivery of bioactive proteins and nucleic acid-based macromolecules and/or provide a suitable microenvironment for the localization and sustenance of reparative progenitor cells after transplantation into or onto the eye. Water-rich hydrogels are ideal vehicles for such cargo, but few have all the qualities desired for novel ophthalmic use, namely in situ gelation speed, cytocompatibility, biocompatibility and capacity to functionalize. We describe here the development of an ophthalmic-compatible crosslinking system using oxidized glutathione (GSSG), a physiologically relevant molecule with a history of safe use in humans. When GSSG is used in conjunction with an existing hyaluronate-based, in situ crosslinkable hydrogel platform, gels form in less than 5min using the thiol–disulfide exchange reaction. This GSSG hydrogel supports the 3-D culture of adipose-derived stem cells in vitro and shows biocompatibility in preliminary intracutaneous and subconjunctival experiments in vivo. In addition, the thiol–disulfide exchange reaction can also be used in conjunction with other thiol-compatible chemistries to covalently link peptides for more complex formulations. These data suggest that this hydrogel could be well suited for local ocular delivery, focusing initially on front of the eye therapies. Subsequent uses of the hydrogel include delivery of back of the eye treatments and eventually into other soft, hyaluronan-rich tissues such as those from the liver and brain. [Copyright &y& Elsevier]

Abstract: Stimuli triggered polymers provide a variety of applications related with the biomedical fields. Among various stimuli triggered mechanisms, thermoresponsive mechanisms have been extensively investigated, as they are relatively more convenient and effective stimuli for biomedical applications. In a contemporary approach for achieving the sustained action of proteins, peptides and bioactives, injectable depots and implants have always remained the thrust areas of research. In the same series, Poloxamer based thermogelling copolymers have their own limitations regarding biodegradability. Thus, there is a need to have an alternative biomaterial for the formulation of injectable hydrogel, which must remain biocompatible along with safety and efficacy. In the same context, poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of their biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review stresses on the physicochemical property, stability and composition prospects of smart PEG/poly(lactic-co-glycolic acid) (PLGA) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. The manuscript also highlights the synthesis scheme and stability characteristics of these copolymers, which will surely help the researchers working in the same area. We have also emphasized the applied use of these smart copolymers along with their formulation problems, which could help in understanding the possible modifications related with these, to overcome their inherent associated limitations. [Copyright &y& Elsevier]

Abstract: Thermosensitive hydrogels based on poly(γ-ethyl-l-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-l-glutamate) triblock copolymers (PELG-PEG-PELG) were prepared for localized and sustained delivery of anticancer drugs. The polypeptide-based hydrogels showed much lower critical gelation concentration than the traditional polyester-based hydrogels. In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for ∼21 days, and H&E staining study suggested acceptable biocompatibility of our materials in vivo. Then the hydrogels were tried as injectable implants to encapsulate antitumor drug, paclitaxel (PTX), to assess the in situ anti-tumoral activity using liver cancer xenograft model. The results demonstrated that the PTX-incorporated hydrogels could efficiently suppress the tumor growth, and did not result in obvious damage to normal organs. Therefore, the polypeptide-based thermosensitive hydrogels designed in the present study have great potential to serve as an effective platform for localized anti-cancer drug delivery. [Copyright &y& Elsevier]

Abstract: Current antimicrobial strategies have mostly been developed to manage infections due to planktonic cells. However, microbes in their nature state will tend to exist by attaching to and growing on living and inanimate surfaces that result in the formation of biofilms. Conventional therapies for treating biofilm-related infections are likely to be insufficient due to the lower susceptibility of microbes that are embedded in the biofilm matrix. In this study, we report the development of biodegradable hydrogels from vitamin E-functionalized polycarbonates for antimicrobial applications. These hydrogels were formed by incorporating positively-charged polycarbonates containing propyl and benzyl side chains with vitamin E moiety into physically cross-linked networks of “ABA”-type polycarbonate and poly(ethylene glycol) triblock copolymers. Investigations of the mechanical properties of the hydrogels showed that the G′ values ranged from 1400 to 1600 Pa and the presence of cationic polycarbonate did not affect the stiffness of the hydrogels. Shear-thinning behavior was observed as the hydrogels displayed high viscosity at low shear rates that dramatically decreased as the shear rate increased. In vitro antimicrobial studies revealed that the more hydrophobic VE/BnCl(1:30)-loaded hydrogels generally exhibited better antimicrobial/antifungal effects compared to the VE/PrBr(1:30) counterpart as lower minimum biocidal concentrations (MBC) were observed in Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and Candida albicans (fungus) (156.2, 312.5, 312.5 mg/L for VE/BnCl(1:30) and 312.5, 2500 and 625 mg/L for VE/PrBr(1:30) respectively). Similar trends were observed for the treatment of biofilms where VE/BnCl(1:30)-loaded hydrogels displayed better efficiency with regards to eradication of biomass and reduction of microbe viability of the biofilms. Furthermore, a high degree of synergistic antimicrobial effects was also observed through the co-delivery of antimicrobial polycarbonates with a conventionally-used antifungal agent, fluconazole. These hydrogels also displayed excellent compatibility with human dermal fibroblasts with cell viability >80% after treatment with hydrogels loaded with cationic polymers and/or fluconazole at minimum biocidal concentrations (MBC). [Copyright &y& Elsevier]

Abstract: The aim of this study was to develop a magnetic thermosensitive hydrogel as intravesical Bacillus Calmette–Guérin (BCG) delivery system, which was formulated with chitosan (CS), β-glycerophosphate (GP) and Fe3O4 magnetic nanoparticle (Fe3O4-MNP). The gelation time and magnetic response of the gel system were investigated. The morphology of the gel was displayed by scanning electron microscope. Frozen section examination was creatively employed for exhibiting the structure of the gel and determining its intravesical residence time. The antitumor effect and local immune activity of BCG loaded magnetic gel were evaluated. The flowing solution of CS/GP under room temperature could gelate rapidly at body temperature both in vitro and in vivo. The magnetic injectable hydrogels significantly prolonged intravesical BCG residence time under an applied magnetic field. In comparison to traditional BCG therapy for superficial bladder tumor, BCG delivered by the gel system induced a stronger Th1 immune response and revealed higher antitumor efficacy. [Copyright &y& Elsevier]

Abstract: Non-viral gene delivery holds great promise for promoting tissue regeneration, and offers a potentially safer alternative than viral vectors. Great progress has been made to develop biodegradable polymeric vectors for non-viral gene delivery in 2D culture, which generally involves isolating and modifying cells in vitro, followed by subsequent transplantation in vivo. Scaffold-mediated gene delivery may eliminate the need for the multiple-step process in vitro, and allows sustained release of nucleic acids in situ. Hydrogels are widely used tissue engineering scaffolds given their tissue-like water content, injectability and tunable biochemical and biophysical properties. However, previous attempts on developing hydrogel-mediated non-viral gene delivery have generally resulted in low levels of transgene expression inside 3D hydrogels, and increasing hydrogel stiffness further decreased such transfection efficiency. Here we report the development of biodegradable polymeric vectors that led to efficient gene delivery inside poly(ethylene glycol) (PEG)-based hydrogels with tunable matrix stiffness. Photocrosslinkable gelatin was maintained constant in the hydrogel network to allow cell adhesion. We identified a lead biodegradable polymeric vector, E6, which resulted in increased polyplex stability, DNA protection and achieved sustained high levels of transgene expression inside 3D PEG-DMA hydrogels for at least 12 days. Furthermore, we demonstrated that E6-based polyplexes allowed efficient gene delivery inside hydrogels with tunable stiffness ranging from 2 to 175 kPa, with the peak transfection efficiency observed in hydrogels with intermediate stiffness (28 kPa). The reported hydrogel-mediated gene delivery platform using biodegradable polyplexes may serve as a local depot for sustained transgene expression in situ to enhance tissue engineering across broad tissue types. [Copyright &y& Elsevier]

Abstract: Metastasis begins with the escape, or dissemination, of cancer cells from the primary tumor. We recently demonstrated that tumors preferentially disseminate into collagen I and not into basement membrane protein gels (Matrigel). In this study, we used synthetic polymer systems to define material properties that could induce dissemination into Matrigel. We first specifically varied rigidity by varying the crosslinking density of poly(ethylene glycol) (PEG) networks within Matrigel scaffolds. Increased microenvironmental rigidity limited epithelial growth but did not promote dissemination. We next incorporated adhesive signals into the PEG network using peptide-conjugated cyclodextrin (α-CDYRGDS) rings. The α-CDYRGDS rings threaded along the PEG polymers, enabling independent control of matrix mechanics, adhesive peptide composition, and adhesive density. Adhesive PEG networks induced dissemination of normal and malignant mammary epithelial cells at intermediate values of adhesion and rigidity. Our data reveal that microenvironmental signals can induce dissemination of normal and malignant epithelial cells without requiring the fibrillar structure of collagen I or containing collagen I-specific adhesion sequences. Finally, the nanobiomaterials and assays developed in this study are generally useful both in 3D culture of primary mammalian tissues and in the systematic evaluation of the specific role of mechanical and adhesive inputs on 3D tumor growth, invasion, and dissemination. [Copyright &y& Elsevier]

Abstract: Intervertebral disc (IVD) degeneration is one of the leading causes of lower back pain and a major health problem worldwide. Current surgical treatments include excision or immobilisation, with neither approach resulting in the repair of the degenerative disc. As such, a tissue engineering-based approach in which stem cells, coupled with an advanced delivery system, could overcome this deficiency and lead to a therapy that encourages functional fibrocartilage generation in the IVD. In this study, we have developed an injectable hydrogel system based on enzymatically-crosslinked polyethylene glycol and hyaluronic acid. We examined the effects of adding pentosan polysulphate (PPS), a synthetic glycosaminoglycan-like factor that has previously been shown (in vitro and in vivo) to this gel system in order to induce chondrogenesis in mesnchymal precursor cells (MPCs) when added as a soluble factor, even in the absence of additional growth factors such as TGF-β. We show that both the gelation rate and mechanical strength of the resulting hydrogels can be tuned in order to optimise the conditions required to produce gels with the desired combination of properties for an IVD scaffold. Human immunoselected STRO-1+ MPCs were then incorporated into the hydrogels. They were shown to retain good viability after both the initial formation of the gel and for longer-term culture periods in vitro. Furthermore, MPC/hydrogel composites formed cartilage-like tissue which was significantly enhanced by the incorporation of PPS into the hydrogels, particularly with respect to the deposition of type-II-collagen. Finally, using a wild-type rat subcutaneous implantation model, we examined the extent of any immune reaction and confirmed that this matrix is well tolerated by the host. Together these data provide evidence that such a system has significant potential as both a delivery vehicle for MPCs and as a matrix for fibrocartilage tissue engineering applications. [Copyright &y& Elsevier]

Abstract: A wide variety of hydrogels have been explored as 3D culture platforms and for applications in tissue engineering. Hydrogels formed from natural extracellular matrix (ECM) proteins readily support the formation of vasculature in vitro, but only a handful of hydrogels composed of synthetic materials have shown anything comparable. This relative lack of synthetic material options has hindered efforts to better understand how ECM cues direct vascularization. We developed a biosynthetic hydrogel consisting of polyethylene glycol diacrylamide conjugated to macromolecular type-I collagen. Through their acrylamide-based crosslinks, these materials allow for independent control of physical properties and bulk ligand concentration. These hydrogels exhibited hydrolytic stability, but the collagen component retained its susceptibility to enzymatic remodeling. Photoencapsulation of endothelial cells and fibroblasts within this hydrogel material and their subsequent co-culture led to the formation of capillary vessel-like networks with well-defined hollow lumens. Capillary formation was prevented by inhibiting matrix metalloproteinase (MMP) activity, recapitulating the MMP-dependence of vascularization observed in natural hydrogels. These findings validate the utility of this material platform to decipher how the ECM regulates capillary morphogenesis and to support the formation of vascularized tissue constructs for potential applications in regenerative medicine. [Copyright &y& Elsevier]

A series of biodegradable hydrogels based on dextran and poly(L-glutamic acid) were fabricated for effective vancomycin loading and release. The preparation of hydrogels was simply achieved by photo cross-linking of methacrylated dextran and poly(L-glutamic acid)- g-hydroxyethyl methacrylate (PGH) in the presence of photoinitiator I2959. The structures of hydrogels were characterized by FTIR and SEM. The swelling and enzymatic degradation behaviors of hydrogels were examined to be dependent on the poly(L-glutamic acid) content in the hydrogels. The higher content of poly(L-glutamic acid) in the gel, the higher swelling ratio and quicker degradation were observed. More interestingly, the hydrogel with higher PGH ratio showed higher vancomycin (VCM) loading content, which might be due to the electrostatic interaction between carboxylate groups in hydrogel and ammonium group of VCM. In vitro drug release from the VCM-loaded hydrogels in aqueous solution exhibited sustained release of VCM up to 72 h, while the in vitro antibacterial test based on the VCM-loaded hydrogel showed an efficient Methicillin-Resistant S. aureus (MRSA) inhibition extending out to 7 days. These results demonstrated that the biodegradable hydrogels which formed by in situ photo-cross linking would be promising as scaffolds or coatings for local antibacterial drug release in tissue engineering. [ABSTRACT FROM AUTHOR]

Highlights: [•] Single and mixed cyclodextrin hydrogels with controlled geometry have been synthesized. [•] Swelling profiles show the similarity of all the networks for single and mixed gels. [•] The Korsmeyer–Peppas model permits to identify in vitro drug release mechanisms. [•] The mixed polymers at pH 1.2 show non-Fickian release behaviour. [•] The coupling of diffusion and macromolecular relaxation mechanisms has been studied. [Copyright &y& Elsevier]

Drug-coated balloons are medical devices designed to locally deliver drug to diseased segments of the vessel wall. For these dosage forms, drug transfer to the vessel wall needs to be examined in detail, since drug released into the blood is cleared from the site. In order to examine drug transfer, a new in vitro setup was developed combining the estimation of drug loss during advancement to the site of application in a model coronary artery pathway with a hydrogel compartment representing, as a very simplified model, the vessel wall. The transfer of fluorescent model substances as well as the drug paclitaxel from coated balloons to the simulated vessel wall was evaluated using this method. The model was suitable to quantify the fractions transferred to the hydrogel and also to qualitatively assess distribution patterns in the hydrogel film. In the case of fluorescein sodium, rhodamin b and paclitaxel, vast amounts of the coated substance were lost during the simulated passage and only very small fractions of about 1% of the total load were transferred to the gel. This must be attributed to good water solubility of the fluorescent substances and the mechanical instability of the paclitaxel coating. Transfer of the hydrophobic model substance triamterene was however nearly unaffected by the preliminary tracking procedure with transferred fractions ranging from 8% to 14%. Analysis of model substance distribution yielded inhomogeneous distributions indicating that the coating was not evenly distributed on the balloon surface and that a great fraction of the coating liquid did not penetrate the folds of the balloon. This finding is contradictory to the generally accepted assumption of a drug depot inside the folds and emphasizes the necessity to thoroughly characterize in vitro performance of drug-coated balloons to support the very promising clinical data. [ABSTRACT FROM AUTHOR]

The article presents various chemistry-related studies featured in "Chemistry & Industry" magazine in 2013. University of Michigan researchers managed to develop superomniphobic surfaces that can repel different types of liquids. Bioengineers at the University of California in San Diego tested the safety of an injectable hydrogel for repairing tissue following a heart attack. University of Oxford researchers developed a reliable procedure for high quality graphene production.

Hydrogel polymers have many applications in regenerative medicine. The aim of this study in dogs was to investigate bone regeneration in dehiscence-type peri-implant defects created surgically and treated with (i) biphasic calcium phosphate (BCP) granules alone; (ii) a composite putty hydroxypropyl methylcellulose (HPMC)/BCP (MBCP/putty); and (iii) a polymer crosslinked membrane of silanized-HPMC (Si-HPMC/BCP) compared with empty controls. At 3 months, new bone formation was significantly more important in defects filled with HPMC/BCP or Si-HPMC/BCP compared with spontaneous healing in control ( P = 0.032 and P = 0.046 respectively) and more substantial compared with BCP alone. Furthermore, new bone formation in direct contact with the implant surface was observed in all three groups treated with BCP. The addition of HPMC to the BCP granules may have enhanced the initial stability of the material within the blood clot in these large and complex osseous defects. The Si-HPMC hydrogel may also act as an occlusive membrane covering the BCP, which could improve the stability of the granules in the defect area. However, the crosslinking time of the Si-HPMC is too long for easy handling and the mechanical properties remain to be improved. The composite MBCP/putty appears to be a valuable bone-graft material in complex defects in periodontology and implantology. These encouraging results should now be confirmed in clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: Microparticles capable of releasing protein drugs are often incorporated into injectable hydrogels to minimize their displacement at an implantation site, reduce initial drug burst, and further control drug release rates over a broader range. However, there is still a need to develop methods for releasing drug molecules over extended periods of time, in order to sustain the bioactivity of drug molecules at an implantation site. In this study, we hypothesized that a hydrogel formed through the cross-linking of pyrrole units linked to a hydrophilic polymer would release protein drugs in a more sustained manner, because of an enhanced association between cross-linked pyrrole groups and the drug molecules. To examine this hypothesis, we prepared hydrogels of alginate substituted with pyrrole groups, alginate-g-pyrrole, through a horse-radish peroxidase (HRP)-activated cross-linking of the pyrrole groups. The hydrogels were encapsulated with poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with vascular endothelial growth factor (VEGF). The resulting hydrogel system released VEGF in a more sustained manner than Ca2+ alginate or Ca2+ alginate-g-pyrrole gel systems. Finally, implantations of the VEGF-releasing HRP-activated alginate-g-pyrrole hydrogel system on chicken chorioallantoic membranes resulted in the formation of blood vessels in higher densities and with larger diameters, compared to other control conditions. Overall, the drug releasing system developed in this study will be broadly useful for regulating release rates of a wide array of protein drugs, and further enhance the quality of protein drug-based therapies. [Copyright &y& Elsevier]

Abstract: Allografts remain the clinical “gold standard” for treatment of critical sized bone defects despite minimal engraftment and ∼60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a ‘tissue engineered periosteum’. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (∼2.4-fold), endochondral bone formation (∼2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification. [Copyright &y& Elsevier]

Abstract: A novel degradable microsphere (MS) for intra-articular drug delivery, composed of a polyethylene glycol (PEG) core containing degradable regions made of short poly-(lactic-co-glycolic acid) (PLGA) sequences – named PEG-hydrogel MS – was injected into the cavity of sheep shoulder joint, and compared to non-degradable MS devoid of hydrolysable crosslinker in terms of location, degradation and inflammation. One week after intra-articular injection both groups of MS were localized beneath the synovial lining of the synovial fringes located at bottom of the shoulder joint, while a fraction of particles remained in synovial fluid. Histological analyses made one and 4 weeks after intra-articular injection showed cell proliferation around the non-degradable MS entrapped within the synovium. By contrast, degradable PEG-hydrogel MS were surrounded by few cells. The degradation of degradable PEG-hydrogel MS within the synovium was slow and was not fully complete after four weeks. Our findings indicate that the tissue entrapment of MS below the synovial lining was independent of the material degradability, while degradable PEG-hydrogel MS are less inflammatory than the non-degradable one. Degradable PEG-hydrogel MS offer several advantages over the non-degradable MS as carriers for a sustained drug delivery in synovial tissue according to the low intensity of inflammatory reaction triggered in synovium. [Copyright &y& Elsevier]

Hydrogels have evolved over the last decade as materials of choice in varied biomedical applications. This is associated with the inherent biocompatible nature of the hydrogels. The modulation of the properties of the hydrogels is easily possible due to the availability of polymers of varied chemistry and physical properties. This review discusses the pharmaceutical aspects of the controlled release of bioactive agents from hydrogel-based formulations. [ABSTRACT FROM PUBLISHER]

Abstract: In this study, an injectable calcium silicate (CS)/sodium alginate (SA) hybrid hydrogel was prepared using a novel material composition design. CS was incorporated into an alginate solution and internal in situ gelling was induced by the calcium ions directly released from CS with the addition of d-gluconic acid δ-lactone (GDL). The gelling time could be controlled, from about 30s to 10min, by varying the amounts of CS and GDL added. The mechanical properties of the hydrogels with different amounts of CS and GDL were systematically analyzed. The compressive strength of 5% CS/SA hydrogels was higher than that of 10% CS/SA for the same amount of GDL. The swelling behaviors of 5% CS/SA hydrogels with different contents of GDL were therefore investigated. The swelling ratios of the hydrogels decreased with increasing GDL, and 5% CS/SA hydrogel with 1% GDL swelled by only less than 5%. Scanning electron microscopy (SEM) observation of the scaffolds showed an optimal interconnected porous structure, with the pore size ranging between 50 and 200μm. Fourier transform infrared spectroscopy and SEM showed that the CS/SA composite hydrogel induced the formation of hydroxyapatite on the surface of the materials in simulated body fluid. In addition, rat bone mesenchymal stem cells (rtBMSCs) cultured in the presence of hydrogels and their ionic extracts were able to maintain the viability and proliferation. Furthermore, the CS/SA composite hydrogel and its ionic extracts stimulated rtBMSCs to produce alkaline phosphatase, and its ionic extracts could also promote angiogenesis of human umbilical vein endothelial cells. Overall, all these results indicate that the CS/SA composite hydrogel efficiently supported the adhesion, proliferation and differentiation of osteogenic and angiogenic cells. Together with its porous three-dimensional structure and injectable properties, CS/SA composite hydrogel possesses great potential for bone regeneration and tissue engineering applications. [Copyright &y& Elsevier]

Abstract: Macroporous elastic scaffolds containing gelatin (4% or 10%) and 0.25% hyaluronic acid (HA) were fabricated by cryogelation for application in adipose tissue engineering. These cryogels have interconnected pores (∼200μm), high porosity (>90%) and a high degree of cross-linking (>99%). The higher gelatin concentration reduced the pore size, porosity and swelling ratio of the cryogel but improved its swelling kinetics. Compressive mechanical testing of cryogel samples demonstrated non-linear stress–strain behavior and hysteresis loops during loading–unloading cycles, but total recovery from large strains. The presence of more gelatin increased the elastic modulus, toughness and storage modulus and yielded a cryogel that was highly elastic, with a loss tangent equal to 0.03. Porcine adipose-derived stem cells (ADSCs) were seeded in the cryogel scaffolds to assess their proliferation and differentiation. In vitro studies demonstrated a good proliferation rate and the adipogenic differentiation of the ADSCs in the cryogel scaffolds, as shown by their morphological change from a fibroblast-like shape to a spherical shape, decreased actin cytoskeleton content, growth arrest, secretion of the adipogenesis marker protein leptin, Oil Red O staining for triglycerides and expression of early (LPL and PPARγ) and late (aP2 and leptin) adipogenic marker genes. In vivo studies of ADSCs/cryogel constructs implanted in nude mice and pigs demonstrated adipose tissue and new capillary formation, the expression of PPARγ, leptin and CD31 in immunostained explants, and the continued expression of adipocyte-specific genes. Both the in vitro and in vivo studies indicated that the gelatin/HA cryogel provided a structural and chemical environment that enabled cell attachment and proliferation and supported the biological functions and adipogenesis of the ADSCs. [Copyright &y& Elsevier]

Abstract: Matrices based on silk fibroin from the non-mulberry silkworm Antheraea mylitta and the mulberry silkworm Bombyx mori have demonstrated good applicability in regenerative medicine. However, the cocoons of A. mylitta are underutilized in part due to their lack of solubility in traditional organic solvents. Therefore, the present work investigates the solubilization and processing of degummed fibers obtained from the cocoons of both silkworm species into hydrogels using ionic liquids (ILs). The developed hydrogels exhibited a rubbery consistency, viscoelastic behavior and rapid degradation in the presence of protease XIV. Scanning electron and confocal microscopy images suggest that human adipose stem cells (hASCs) are able to adhere to and migrate at different levels within the hydrogel structures. Moreover, the MTS assay demonstrated the maintenance of cell metabolic activity for up to 28days, while DNA quantification showed that hASCs were able to proliferate on the seeded hydrogels. The findings indicate that complete IL removal from the fabricated hydrogels results in a positive hASCs cellular response. Thus the present approach provides a unique opportunity to broaden the processability and application of silk fibroin obtained from A. mylitta cocoons for regenerative medicine, namely cartilage regeneration. [Copyright &y& Elsevier]

Abstract: This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(d l-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7days and PLGA microparticle-loaded constructs releasing colistin for up to 8weeks. Three formulations with either burst release or extended release at different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2×107 colony forming unitsml−1). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12weeks on culture of the defect, saliva, or blood. Defects with high dose extended release implants had greater soft tissue healing compared with defects with burst release implants, with 8 of 10 animals showing healed mucosae compared with 2 of 10 respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing compared with implants with burst release of colistin from a gelatin carrier. [Copyright &y& Elsevier]

Abstract: Many vitamins, bioactive lipids and over 40% of newly developed drugs are hydrophobic, and their poor water solubility limits their delivery using conventional formulations. In this work we investigated a composite gel system formulated from microemulsions embedded in alginate hydrogels, and showed that it is capable of loading several hydrophobic compounds with a wide range of aqueous solubility. All gels were clear, with no precipitations, indicating the solubility of the drugs in the gels. The release behavior was similar for different microemulsion formulations, various drugs and increasing concentrations of a drug. These findings indicate that our system could potentially act as a generic system, where the properties of the release do not depend on the drug but rather on the attributes of the gel. The structure of composite gels was investigated using small-angle scattering of X-rays and neutrons (SAXS and SANS, respectively). SANS showed more sensitivity to the structure of the microemulsion in the composite gel than SAXS did. SAXS and SANS plots of the composite gels show that both the droplets and the gel network preserve their structure when mixed together. [Copyright &y& Elsevier]

Abstract: Hydrogels are finding increased clinical utility as advances continue to exploit their favorable material properties. Hydrogels can be adapted for many applications, including surface coatings and drug delivery. Anti-infectious surfaces and delivery systems that actively destroy invading organisms are alternative ways to exploit the favorable material properties offered by hydrogels. Sterilization techniques are commonly employed to ensure the materials are non-infectious upon placement, but sterilization is not absolute and infections are still expected. Natural, anti-bacterial proteins have been discovered which have the potential to act as anti-infectious agents; however, the proteins are toxic and need localized release to have therapeutic efficacy without toxicity. In these studies, we explore the use of the glutathione s-transferase (GST) to anchor the bactericidal peptide, melittin, to the surface of poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We show that therapeutic levels of protein can be anchored to the surface of the microspheres using the GST anchor. We compared the therapeutic efficacy of recombinant melittin released from PEGDA microspheres to melittin. We found that, when released by an activating enzyme, thrombin, recombinant melittin efficiently inhibits growth of the pathogenic bacterium Streptococcus pyogenes as effectively as melittin created by solid phase peptide synthesis. We conclude that a GST protein anchor can be used to immobilize functional protein to PEGDA microspheres and the protein will remain immobilized under physiological conditions until the protein is enzymatically released. [Copyright &y& Elsevier]

Abstract: Impairment of sphincter muscles or their neural and vascular support leads to stress urinary incontinence. The aim of this study was to determine the role of urine-derived stem cells (USCs) over-expressing vascular endothelial growth factor (VEGF) in collagen-I gel on angiogenesis, cell survival, cell growth, myogenic phenotype differentiation of the implanted cells and innervations following implantation in vivo. USCs were infected with adenovirus containing the human VEGF165 and green fluorescent protein genes. A total of 5 × 106 cells, USCs alone, or plus endothelial cells or human skeletal myoblasts (as control) suspended in collagen-I gel were subcutaneously implanted into nude mice. Extensive vascularization and more implanted cells was noted in VEGF-expressing USCs groups compared to the non-VEGF groups in vivo. Numbers of the cells displaying endothelial markers (CD 31 and von Willebrand's factor) and myogenic markers (myf-5, MyoD and desmin), and regenerated nerve fibers displaying neural markers (S-100, GFAP and neurofilament) significantly increased in the grafts of VEGF-expressing USCs. Improved angiogenesis by VEGF-expressing USCs enhanced grafted cell survival, recruited the resident cells and promoted myogenic phenotype differentiation of USCs and innervation. This approach has important clinical implications for the development of cell therapies for the correction of stress urinary incontinence. [Copyright &y& Elsevier]

ABSTRACT To improve the alkali and heat resistances of Cl+Me-isothiazolinone (MCI/MI), a calcium alginate (CA) hydrogel sphere was used as the carrier for MCI/MI, and an MCI/MI/CA hydrogel sphere was prepared. Then, the release properties, alkali-resistance and heat-resistance properties, long-term antibacterial performance, and cytotoxicity of this novel hydrogel sphere were investigated. The results show that the CA hydrogel sphere released MCI/MI in a sustained manner with long-term antibacterial activity. Moreover, the CA hydrogel sphere improved the alkali and heat resistances of the MCI/MI. More importantly, this hydrogel sphere showed a slight cytotoxicity, which suggested that the MCI/MI/CA hydrogel sphere would be an easily added antibacterial hydrogel sphere for a wide range of products. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1554-1561, 2013 [ABSTRACT FROM AUTHOR]

Abstract: Tretinoin (TRE) is a widely used retinoid for the topical treatment of acne, psoriasis, skin cancer and photoaging. Despite unmatchable efficacy, it is associated with several vexatious side effects like marked skin erythema, peeling and irritation, eventually leading to poor patient compliance. Its photo-instability and high lipophilicity also pose challenges in the development of a suitable topical product. The present study, therefore, aims to develop biocompatible lipid-based nanocarriers of TRE to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy. The TRE-loaded liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs) were prepared and characterized for micromeritics, surface charge, percent drug efficiency and morphology. Bioadhesive hydrogels of the developed systems were also evaluated for rheological characterization, photostability, ex vivo skin permeation and retention employing porcine skin, and anti-psoriatic activity in mouse tail model. Nanoparticulate carriers (SLNs, NLCs) offered enhanced photostability, skin transport and anti-psoriatic activity vis-à-vis the vesicular carriers (liposomes, ethosomes) and the marketed product. However, all the developed nanocarriers were found to be more biocompatible and effective than the marketed product. These encouraging findings can guide in proper selection of topical carriers among diversity of such available carriers systems. [Copyright &y& Elsevier]

Abstract: To study the release of liposome-associated drugs into hydrogels, we designed and synthesized two pH-sensitive rhodamine derivatives to use as model compounds of different lipophilicities. The dyes were fluorescent when in the free form released from liposomes into the chitosan hydrogel, but not when incorporated within liposomes. The effect of liposomal composition, surface charge and vesicle size on the release of those incorporated dyes was evaluated. The lipophilicity of the rhodamine derivatives affected both the amount and rate of release. While liposome size had only a minor effect on the release of dyes into the hydrogel, the surface charge affected the release to a greater extent. By optimizing the characteristics of liposomes we could develop a liposomes-in-hydrogel system for application in wound therapy. We further characterized liposomes-in-hydrogel for their rheological properties, textures and moisture handling, as well as their potential to achieve a controlled release of the dye. The polymer-dependent changes in the hydrogel properties were observed upon addition of liposomes. The charged liposomes exhibited stronger effects on the textures of the chitosan hydrogels than the neutral ones. In respect to the ability of the system to handle wound exudates, chitosan-based hydrogels were found to be superior to Carbopol-based hydrogels. [Copyright &y& Elsevier]

The objective of this study was to develop a novel antimicrobial seaweed wound dressing. The seaweed extract was active against nine clinically-relevant wound pathogens. A hydrogel formulation was prepared using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), followed by addition of 1% seaweed extract. The antimicrobial properties of the novel dressing were tested using agar diffusion assays, with release-profiles examined using gel leaching and gel transfer assays. The dressing was found to be effective against the same microbial strains as the seaweed extract, with similar efficacy to the commonly used silver-based dressing, Acticoat®. Antimicrobial release-profile assays revealed that the dressing was effective in inhibiting 70–90% of the bacterial population within the first 30min, followed by a long, sustained released up to 97h, without leaving a residue following five subsequent transfers of the dressing. Antimicrobial activity was stable for up to 6 months of storage at 4°C, but activity was reduced slightly after 15 weeks. Following autoclave sterilization, the dressing displayed a slower release profile compared to a non-autoclaved counterpart. Hence, the seaweed dressing may have commercial applications, potentially competing with silver-based dressings at a lower cost per-application. This is the first report of development of a seaweed-based antimicrobial dressing. [ABSTRACT FROM AUTHOR]

Aims/Introduction To realize the effectiveness of a novel system for measuring glucose area under the curve ( AUC) using minimally invasive interstitial fluid extraction technology ( MIET), outpatients undergoing oral glucose tolerance tests ( OGTT) were investigated for the efficacy of screening for glucose intolerance using this system. Materials and Methods Fifty outpatients scheduled to undergo a 75-g OGTT for medical reasons were recruited to the study. An area of skin on the forearm was pretreated with microneedle arrays before the application of hydrogels for interstitial fluid extraction. Plasma glucose ( PG) levels were measured every 30 min for 2 h to calculate reference (actual) AUC. The AUC was predicted by MIET on the basis of glucose extracted by the hydrogel using sodium ion levels as the internal standard. Results Good correlation between MIET-predicted and reference AUCs obtained using PG levels was confirmed for a wide AUC range. By introducing a threshold level for AUC to separate glucose intolerance with peak glucose ≥180 mg/dL from normal glucose tolerance, the system was demonstrated to provide better screening accuracy compared with conventional methods that use Hb A1c and fasting PG levels. The results of a questionnaire-based survey administered to the subjects suggested that this system was readily accepted by the majority as a painless monitoring method. Conclusions The findings suggest that our glucose AUC measurement system using MIET would be useful for screening of glucose intolerance. In the future, this system may prove to be a useful aid as a screen for glucose intolerance before performing an OGTT for diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: High ratios of fresh frozen plasma:packed red blood cells in damage control resuscitation (DCR) are associated with increased survival. The impact of volume and type of resuscitative fluid used during high ratio transfusion has not been analyzed. We hypothesize a difference in outcomes based on the type and quantity of resuscitative fluid used in patients that received high ratio DCR. Methods: A matched case control study of patients who received transfusions of ≥ four units of PRBC during damage control surgery over 4 1/2 y, was conducted at a Level I Trauma Center. All patients received a high ratio DCR, >1:2 of fresh frozen plasma:packed red blood cells. Demographics and outcomes of the type and quantity of resuscitative fluids used in combination with high ratio DCR were compared and analyzed. A Kaplan-Meier survival analysis was computed among four groups: colloid (median quantity = 1.0 L), <3 L crystalloid, 3–6 L crystalloid, and >6 L crystalloid. Results: There were 56 patients included in the analysis (28 in the crystalloid group and 28 in the colloid group). Demographics were statistically similar. Intraoperative median units of PRBC: crystalloid versus colloid groups was 13 (IQR 8-21) versus 16 (IQR 12–19), P = 0.135; median units of FFP: 12 (IQR 7–18) versus 12 (IQR 10–18), P = 0.440. OR for 10-d mortality in the crystalloid group was 8.41 [95% CI 1.65–42.76 (P = 0.01)]. Kaplan-Meier survival analysis demonstrated lowest mortality in the colloid group and higher mortality with increasing amounts of crystalloid (P = 0.029). Conclusions: During high ratio DCR, resuscitation with higher volumes of crystalloids was associated with an overall decreased survival, whereas low volumes of colloid use were associated with increased survival. In order to improve outcomes without diluting the survival benefit of hemostatic resuscitation, guidelines should focus on effective low volume resuscitation when high ratio DCR is used. A multi-institutional analysis is needed in order to validate these results. [Copyright &y& Elsevier]

Highlights: [•] We employed hydrogel nanoparticles to concentrate urinary hGH into the linear range of isoform differential immunoassays. [•] The pre-processing step allowed measurement of urine spiked with recombinant and pituitary hGH. [•] Nanoparticles pre-treatment was applied to urine from healthy volunteers administered with recombinant hGH. [•] The recombinant/pituitary hGH concentration ratios remained above the established WADA criterion for hGH misuse up to 24h after the last administration dose. [•] The use of nanoparticles appears to open the possibility of assessing rhGH misuse in urine. [ABSTRACT FROM AUTHOR]

Interpenetrating polymer network hydrogel beads of pectin and sodium carboxymethyl xanthan were prepared by ionotropic gelation with Al-3 ions and covalent cross-linking with glutaraldehyde for sustained delivery of diltiazem hydrochloride. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning colorimetry and scanning electron microscopy were used to characterise the hydrogel beads. The swelling of the hydrogel and the release of drug were relatively low in pH 1.2 buffer solutions. However, higher swelling and drug release were observed in pH 6.8 buffer solutions. The carboxyl functional groups of hydrogels undergo ionisation and the osmotic pressure inside the beads increases resulting in higher swelling and drug release in higher pH. The release of drug depends on concentration of polymer, amount and exposure time of cross-linker and drug content in the hydrogel matrices. The present study indicated that the hydrogel beads minimised the drug release in pH 1.2 buffer solutions and to prolong the drug release in pH 6.8 buffer solutions. [ABSTRACT FROM AUTHOR]

Abstract: Our objective was to characterize the elasticity of hydrogel formulations intended to mimic physical properties that cells and tissues experience in vivo. Using atomic force microscopy (AFM), we tested a variety of concentrations in a variety of biomaterials, including agarose, alginate, the collagens, fibrin, hyaluronic acid, kerateine, laminin, Matrigel, polyacrylamide, polyethylene glycol diacrylate (PEGDA) and silicone elastomer (polydimethylsiloxane). Manipulations of the concentration of biomaterials were detectable in AFM measurements of elasticity (Young′s modulus, E), and E tended to increase with increased concentration. Depending on the biomaterials chosen, and their concentrations, generation of tunable biocompatible hydrogels in the physiologic range is possible. [Copyright &y& Elsevier]

Biopolymer-based materials are based on re-growing resources and are attractive for biomedical applications, as they can inherently combine degradability in vivo, can offer sites of adhesion for cells and proteins, often show good biocompatibility and may additionally be used to release embedded bioactive molecules. However, their selection and efficient use for specific applications require an understanding of molecular principles and relationships between the molecular and macroscopic level to establish distinct properties and functions. Here, synthetic routes are described, which allow tailoring properties and functions of biopolymer-based materials. The biological evaluation of such materials is discussed, with a special emphasis on their application in controlled release systems such as hydrogels and particulate carriers. [ABSTRACT FROM AUTHOR]

Background: Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems. Aim: The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin. Methods: Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels. Results: Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin. Conclusion: A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin. [ABSTRACT FROM AUTHOR]

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable conditions of use and prolonged action. [ABSTRACT FROM AUTHOR]

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64. [ABSTRACT FROM AUTHOR]

Currently, there is no effective strategy for the treatment of spinal cord injury (SCI). A suitable combination of modern hydrogel materials, modified to effectively bridge the lesion cavity, combined with appropriate stem cell therapy seems to be a promising approach to repair spinal cord damage. We demonstrate the synergic effect of porosity and surface modification of hydrogels on mesenchymal stem cell (MSC) adhesiveness in vitro and their in vivo survival in an experimental model of SCI. MSCs were seeded on four different hydrogels: hydroxypropylmethacrylate-RGD prepared by heterophase separation (HPMA-HS-RGD) and three other hydrogels polymerized in the presence of a solid porogen: HPMA-SP, HPMA-SP-RGD, and hydroxy ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACl). Their adhesion capability and cell survival were evaluated at 1, 7, and 14 days after the seeding of MSCs on the hydrogel scaffolds. The cell-polymer scaffolds were then implanted into hemisected rat spinal cord, and MSC survival in vivo and the ingrowth of endogenous tissue elements were evaluated 1 month after implantation. In vitro data demonstrated that HEMA-MOETACl and HPMA-SP-RGD hydrogels were superior in the number of cells attached. In vivo, the highest cell survival was found in the HEMA-MOETACl hydrogels; however, only a small ingrowth of blood vessels and axons was observed. Both HPMA-SP and HPMA-SP-RGD hydrogels showed better survival of MSCs compared with the HPMA-HS-RGD hydrogel. The RGD sequence attached to both types of HPMA hydrogels significantly influenced the number of blood vessels inside the implanted hydrogels. Further, the porous structure of HPMA-SP hydrogels promoted a statistically significant greater ingrowth of axons and less connective tissue elements into the implant. Our results demonstrate that the physical and chemical properties of the HPMA-SP-RGD hydrogel show the best combination for bridging a spinal cord lesion, while the HEMA-MOETACl hydrogel serves as the best carrier of MSCs. [ABSTRACT FROM AUTHOR]

Abstract: We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low βIII tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals. [Copyright &y& Elsevier]

In vitro and in vivo experimentation of various synthetic polymer hydrogels was conducted to establish some of the integral material properties that influence hemostasis. In vitro swelling experiments suggested that positive electrostatic charge was a key determinant of the ability of a polymer hydrogel to absorb physiological fluids, e.g. human plasma and blood. In vitro testing using unadulterated sheep blood suggested positive electrostatic charge and crosslink density were key determinants of the ability of a material to induce or enhance clot formation. Hydrogel formulations composed of higher amounts of positive electrostatic charge and lower crosslink density were able to effectively induce and enhance clot formation in the presence of a coagulation cascade activator. In vivo experimentation confirmed that hydrogels containing higher electrostatic charge and low crosslink density are more effective at fostering the formation of a robust hemostatic plug to control blood loss. [ABSTRACT FROM AUTHOR]

Abstract: Chondroitinase ABC (ChABC) is a promising therapeutic for spinal cord injury as it can degrade the glial scar that is detrimental to regrowth and repair. However, the sustained delivery of bioactive ChABC is a challenge requiring highly invasive methods such as intra-spinal injections, insertion of intrathecal catheters, or implantation of delivery vehicles directly into the tissue. ChABC is thermally unstable, further complicating its delivery. Moreover, there are no commercial antibodies available for its detection. To achieve controlled release, we designed an affinity-based system that sustained the release of bioactive ChABC for at least 7days. ChABC was recombinantly expressed as a fusion protein with Src homology domain 3 (SH3) with an N-terminal histidine (HIS) tag and a C-terminal FLAG tag (ChABC–SH3). Protein purification was achieved using a nickel affinity column and, for the first time, direct quantification of ChABC down to 0.1nM was attained using an in-house HIS/FLAG double tag ELISA. The release of active ChABC–SH3 was sustained from a methylcellulose hydrogel covalently modified with an SH3 binding peptide. The rate of release was tunable by varying either the binding strength of the SH3-protein/SH3-peptide pair or the SH3-peptide to SH3-protein ratio. This innovative system has the potential to be used as a platform technology for the release and detection of other proteins that can be expressed using a similar construct. [Copyright &y& Elsevier]