Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices

Novel polyampholyte hydrogels based on carboxymethyl chitosans (CMC) of various degree of deacetylation (DD) and substitution (DS) were prepared by crosslinking with glutaraldehyde. The hydrogel showed typical amphoteric character responding to pH of the external medium. At the isoelectric point (IEP), the hydrogel shrunk most, when the pH deviated from IEP, the swelling degree (Ds) increased. With increasing DD or DS value, the hydrogel changed from polyampholyte into polycations or polyanions, respectively. Osmotic forces and intermolecular interactions among CMC chains regulate the swelling behavior of CMC gel. The carboxymethyl chitin hydrogels were loaded with bovine blood proteins (BSA), and their release studies were performed in both the simulated gastric and intestinal pH conditions. The release was much quicker in pH 7.4 buffer than pH 1.2 solution; the release followed Fickian diffusion in the first 4h and then steadily increased with the dissolution of the hydrogels.     

Effects of PEG hydrogel crosslinking density on protein diffusion and encapsulated islet survival and function

The rational design of immunoprotective hydrogel barriers for transplanting insulin-producing cells requires an understanding of protein diffusion within the hydrogel network and how alterations to the network structure affect protein diffusion. Hydrogels of varying crosslinking density were formed via the chain polymerization of dimethacrylated PEG macromers of varying molecular weight, and the diffusion of six model proteins with molecular weights ranging from 5700 to 67,000 g/mol was observed in these hydrogel networks. Protein release profiles were used to estimate diffusion coefficients for each protein/gel system that exhibited Fickian diffusion. Diffusion coefficients were on the order of 10(-6)-10(-7) cm(2)/s, such that protein diffusion time scales (t(d) = L(2)/D) from 0.5-mm thick gels vary from 5 min to 24 h. Adult murine islets were encapsulated in PEG hydrogels of varying crosslinking density, and islet survival and insulin release was maintained after two weeks of culture in each gel condition. While the total insulin released during a 1 h glucose stimulation period was the same from islets in each sample, increasing hydrogel crosslinking density contributed to delays in insulin release from hydrogel samples within the 1 h stimulation period.     

Reagent-free crosslinking of aqueous gelatin: manufacture and characteristics of gelatin gels irradiated with gamma-ray and electron beam

In order to obtain a gelatin hydrogel crosslinked by a reagent-free method, gamma-ray and electron beam radiation was applied to porcine, bovine and fish gelatin gels and the products were characterized by measuring the gel fraction, the swelling ratio and the enzymatic degradability. On increasing the radiation dose, the gel fraction increased and both the swelling ratio and the enzymatic degradability decreased. The transition temperature from gel to sol of the hydrogel containing more than 5% mammal gelatins increased up to more than 90 degrees C when gamma-ray or electron beam were irradiated by more than 10 kGy. The results show that the degree of crosslinking of irradiated gelatin hydrogels increases with increasing irradiation dose and with decreasing concentration. It is suggested that the radiation crosslinking occurs around the physical crosslinking point or multiple helix structure of gelatin gel.     

Biodegradable hydrophobic-hydrophilic hybrid hydrogels: swelling behavior and controlled drug release

The objective of this work was to investigate a new family of hydrophobic-hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL-Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and 0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine methiodide, was used as the model drug for the release study from the hybrid hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors' feed ratio, and there were several-fold differences in swelling ratios between a pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of the hydrophobic PGCL-Ma component significantly reduced the initial burst swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios, the swelling data during the early period obeyed either Fickian diffusion (for 50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and 100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex-Ma). A wide range of cocaine methiodide release profiles was achieved by controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug burst release was significantly reduced as the concentration of the hydrophobic PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine methiodide released during the 160-h period was via diffusion-controlled mechanism, while degradation-controlled mechanism dominated thereafter.     

Fluconazole release from hydrogels including acrylamide-acrylic acid-itaconic acid, and their microbiological interactions

Polyacrylamide (PAAm), polyacrylic acid (PAA), poly(acrylamide-co-itaconic acid) (PAAmIA) and poly(acrylic acid-co-itaconic acid) (PAAIA) hydrogels were prepared via free-radical polymerization using ethylene glycol dimethacrylate (EGDMA) as cross-linker. The variations of swelling percentages with time and pH were determined for these hydrogels at 37 degrees C. PAAmIA was found as the most swollen hydrogel at pH 4.0. SEM micrographs were taken to observe the morphology of the hydrogels. The less swollen hydrogel, PAAIA, displays less porosity relative to PAAmIA hydrogel. Fluconazole was entrapped into PAAmIA and PAAIA hydrogels and the release was investigated in Britton-Robinson buffer solution (BR) at pH 4.0 and 37 degrees C. The kinetic release parameters of the hydrogels, n and k, were calculated and Fickian-type diffusion was established for PAAmIA, which releases Fluconazole faster than PAAIA hydrogel. Therapeutic range was reached in the first hour for both hydrogels. Microbiological interactions of hydrogels were also studied in vitro in vaginal medium. It is found that Fluconazole entrapped in hydrogels inhibited the growth of Candida albicans.     

Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities.

Biodegradable gelatin hydrogels were prepared through the glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 and the basic gelatin with an IEP of 9.0. The hydrogel water content was changed by the concentration of both gelatin and glutaraldehyde, used for hydrogel preparation. An aqueous solution of basic fibroblast growth factor (bFGF) was sorbed into the gelatin hydrogel freeze-dried to obtain a bFGF-incorporating gelatin hydrogel. Irrespective of the hydrogel water content, approximately 30% of the incorporated bFGF was released from the bFGF-incorporating acidic gelatin hydrogel, within the first day into phosphate-buffered saline solution at 37 degrees C, followed by no substantial release. Probably, the basic bFGF complexed with the acidic gelatin through poly-ion complexation would not be released under the in vitro non-degradation condition of gelatin. On the contrary, almost 100% of the incorporated bFGF was initially released from all types of basic gelatin hydrogels. This is due to the simple diffusion of bFGF because of no complexation between bFGF and the basic gelatin. When implanted subcutaneously into the mouse back, bFGF-incorporating acidic and basic gelatin hydrogels with higher water contents were degraded with time faster than those with lower water contents. Significant neovascularization was induced around the implanted site of the bFGF-incorporating acidic gelatin hydrogel. The induction period prolonged with the decrease in hydrogel water content. On the other hand, such a prolonged vascularization effect was not achieved by the bFGF-incorporating basic gelatin hydrogel and the hydrogel initially exhibited less enhanced effect, irrespective of the water content. These findings indicate that the controlled release of biologically active bFGF is caused by biodegradation of the acidic gelatin hydrogel, resulting in induction of vascularization effect dependent on the water content. It is possible that only the transient vascularization by the basic gelatin hydrogel is due to the initial large burst in bFGF release, probably because of the down regulation of bFGF receptor.     

Thermosensitive chitosan-gelatin-glycerol phosphate hydrogel as a controlled release system of ferulic acid for nucleus pulposus regeneration

In the degenerative disc, overproduction of reactive oxygen species (ROS) involves in apoptosis and senescence of nucleus pulposus (NP) cells that could accelerate the degenerative process. Ferulic acid (FA) has been reported to have an excellent antioxidant property. In the study, injectable thermosensitive chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel was applied as a controlled release system for FA delivery. The study was aimed to evaluate possible therapeutic effects of FA-incorporated C/G/GP hydrogel on hydrogen peroxide (H(2)O(2))-induced oxidative stress NP cells. The results showed that the release of FA from C/G/GP hydrogel could decrease the H(2)O(2)-induced oxidative stress. Post-treatment of FA-incorporated C/G/GP hydrogel on H(2)O(2)-induced oxidative stress NP cells showed up-regulation of Aggrecan and type II collagen and down-regulation of MMP-3 in mRNA level. The results of sulfated-glycosaminoglycans (GAGs) to DNA ratio and alcian blue staining revealed that the GAGs production of H(2)O(2)-induced oxidative stress NP cells could reach to normal level. The results of caspase-3 activity and TUNEL staining indicated that FA-incorporated C/G/GP hydrogel decreased the apoptosis of H(2)O(2)-induced oxidative stress NP cells. The results suggested that the C/G/GP hydrogel was very suitable for sustained delivery of FA. The FA-incorporated C/G/GP hydrogel would be used to treat the degenerative disc in the early stage before it developed into the latter irreversible stages.     

Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates

Dextran hydrogels were formed in situ by enzymatic crosslinking of dextran-tyramine conjugates and their mechanical, swelling and degradation properties were evaluated. Two types of dextran-tyramine conjugates (M(n,dextran)=14k, M(w)/M(n)=1.45), i.e. dextran-tyramine linked by a urethane bond (denoted as Dex-TA) or by an ester-containing diglycolic group (denoted as Dex-DG-TA), with different degrees of substitution (DS) were prepared. Hydrogels were rapidly formed under physiological conditions from Dex-TA DS 10 or 15 and Dex-DG-TA DS 10 at or above a concentration of 2.5 wt% in the presence of H(2)O(2) and horseradish peroxidase (HRP). The gelation time ranged from 5s to 9 min depending on the polymer concentration and HRP/TA and H(2)O(2)/TA ratios. Rheological analysis showed that these hydrogels are highly elastic. The storage modulus (G'), which varied from 3 to 41 kPa, increased with increasing polymer concentration, increasing HRP/TA ratio and decreasing H(2)O(2)/TA ratio. The swelling/degradation studies showed that under physiological conditions, Dex-TA hydrogels are rather stable with less than 25% loss of gel weight in 5 months, whereas Dex-DG-TA hydrogels are completely degraded within 4-10d. These results demonstrate that enzymatic crosslinking is an efficient way to obtain fast in situ formation of hydrogels. These dextran-based hydrogels are promising for use as injectable systems for biomedical applications including tissue engineering and protein delivery.     

Gelatin-Based Emulsion Gels for Diffusion-Controlled Release Applications

Emulsion gels are now emerging as a new class of biomaterials for controlled-release applications. Novel food-grade emulsion gels consisting of indomethacin-loaded vegetable oil droplets dispersed within genipin-cross-linked gelatin-based hydrogels were characterized for their physical and drug-release properties. Varying the weight ratio of the aqueous and oil phases between 5:1 and 5:5 was used to modulate construct swelling and drug release. The dispersed oil droplets generally became larger, more polydispersed and aggregated with an increase in oil fraction. Cross-linking with genipin increased the puncture strength of the gels vs. their uncross-linked counterparts and was necessary to prevent breakdown. Swelling of the emulsion gels demonstrated Fickian behaviour at all gelatin: oil ratios. Indomethacin release followed Fickian diffusion at higher oil fractions only, demonstrating coupled Fickian and super-Case-II transport at lower oil ratios (5:1, 5:2 and 5:3). Overall, the introduction of a dispersed oil phase within a hydrogel was exploited for the release of hydrophobic bioactive compounds, with tailoring of composition used to significantly alter release kinetics.     

Gelatin-based emulsion gels for diffusion-controlled release applications

Emulsion gels are now emerging as a new class of biomaterials for controlled-release applications. Novel food-grade emulsion gels consisting of indomethacin-loaded vegetable oil droplets dispersed within genipin-cross-linked gelatin-based hydrogels were characterized for their physical and drug-release properties. Varying the weight ratio of the aqueous and oil phases between 5:1 and 5:5 was used to modulate construct swelling and drug release. The dispersed oil droplets generally became larger, more polydispersed and aggregated with an increase in oil fraction. Cross-linking with genipin increased the puncture strength of the gels vs. their uncross-linked counterparts and was necessary to prevent breakdown. Swelling of the emulsion gels demonstrated Fickian behaviour at all gelatin: oil ratios. Indomethacin release followed Fickian diffusion at higher oil fractions only, demonstrating coupled Fickian and super-Case-II transport at lower oil ratios (5:1, 5:2 and 5:3). Overall, the introduction of a dispersed oil phase within a hydrogel was exploited for the release of hydrophobic bioactive compounds, with tailoring of composition used to significantly alter release kinetics.     

Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices

This study examined the interrelated effect of environmental pH, gelatin backbone modification and crosslinking modality on hydrogel morphology, surface hydrophilicity, in vitro swelling/degradation kinetics, in vitro drug release kinetics and in vivo degradation, inflammatory response and drug release activity. The percent glutaraldehyde fixation had a greater impact on the morphology of the dehydrated hydrogels than gelatin modification. Any decrease in percent glutaraldehyde fixation and/or modification of gelatin with polyethylene glycol dialdehyde (PEG-dial) and/or ethylenediaminetetraacetic dianhydride (EDTAD) increased hydrogel surface hydrophilicity. Swelling/degradation studies showed that modification of gelatin with PEG-dial generally increased the time to reach the maximum swelling weight ratio (T(max)) and the time to failure by hydrolysis (T(fail)), but had little effect on the maximum swelling weight ratio (R(max)) and the weight ratio at failure (R(fail)). Modification of gelatin with EDTAD generally had no effect on T(max) and T(fail), but increased R(max) and R(fail). Modification of gelatin with PEG-dial and EDTAD increased R(max), but had no effect on T(max), R(fail), or T(fail). Decreasing percent glutaraldehyde fixation generally increased R(max) and R(fail) but decreased T(max) and T(fail). Decreasing environmental pH from 7.4 to 4.5 had no effect on any swelling/degradation properties. In vitro drug release studies showed that modification of gelatin with PEG-dial and/or EDTAD generally decreased the maximum mass ratio of drug released (D(max)) and the time to reach D(max) (T(dmax)). Percent glutaraldehyde fixation did not significantly affect D(max) or T(dmax) (except for EDTAD-modified gelatin hydrogels). In vivo studies showed that gelatin-based hydrogels elicited comparable levels of acute and chronic inflammatory response as that of the empty cage control by 21 d.     

Doxycycline hydrogels with reversible disulfide crosslinks for dermal wound healing of mustard injuries

Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H(2)O(2) hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (< 1.5%). Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm(3)) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post-exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal re-epithelialization and wound healing. Histology studies of skin showed that doxycycline loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in an SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries.     

Highly stretchable HA/SA hydrogels for tissue engineering

A highly stretchable hyaluronic acid (HA)/sodium alginate (SA) hydrogel was developed in this study based on an interpenetrating polymer network. HA/SA hydrogels were prepared by mixing two polysaccharides followed by covalent crosslinking via epoxy groups on HA molecules and ionic crosslinking via divalent ions on SA chains sequentially. The effect of HA/SA ratio on the pore size and distribution, swelling ratio, elongation and rheological properties as well as protein loading and release properties of HA/SA hydrogels was explored. Moreover, a surface modification method, layer-by-layer (LBL) assembly technique, was applied to modify the hydrogel to evaluate the hydrogel’s tenability in varying biological performance. It was then shown that the hydrogels had the pore sizes ranging from 100 to 50 μm. With the increase in SA content of the resulting hydrogels, the pore size, swelling ratio, and storage modulus (G′) and loss modulus (G″) of the hydrogel all decreased, whereas the in vitro bulk weight loss was fastened. Moreover, elongation at break (EB) value increased first, reached a peak value and then decreased, that is HA8/SA1 (HA:SA = 8:1) had the highest EB value of 417%. This hydrogel could retain 33.2% of the pre-loaded protein even after 72 h, which could be further attenuated when LBL was used to shell the hydrogel. The growth of fibroblasts on HA8/SA1 hydrogel gave preliminary assessment on its suitability as a cellular carrier, while the LBL modified HA8/SA1 hydrogel also favored the anchoring of keratinocytes, further enhancing its cell carrier role for tissue regeneration, especially skin engineering.     

Gelatin hydrogels cross-linked by gamma-ray irradiation: materials for absorption and release of dye

Gelatin hydrogels cross-linked by y-ray irradiation using 60Co as gamma-ray source were prepared. As a model of controlled release of low-molecular-weight compounds, absorption and release of methylene blue, a water-soluble cationic dye, was investigated. Irradiated gelatin hydrogels did not redissolve at temperatures over 40 degrees C, while unirradiated gels were thermoplastic and reversibly changed the stage between gel and sol. Measurement of both the wet weight after swelling in distilled water and dry weight after freeze-drying showed that the higher-dose irradiation gave stiffer and more compact gels with the lower specific water content, irrespective of the absorbed dose rate. The time-course of absorption and release of methylene blue in aqueous solution was measured. Since absorption of dye into gelatin gels was much affected by liquid phase pH, amount of absorption was higher in pH above an IEP of gelatins. Moreover, the absorption and release of methylene blue with Type-B gelatin were higher than with Type-A gelatin, respectively. Therefore, absorption and release of the dye depend on the electrostatic interaction between the dye molecule and gelatin.     

Biodegradation of hydrogel carrier incorporating fibroblast growth factor.

In vivo release of basic fibroblast growth factor (bFGF) from a biodegradable gelatin hydrogel carrier was compared with the in vivo degradation of hydrogel. When gelatin hydrogels incorporating 125I-labeled bFGF were implanted into the back subcutis of mice, the bFGF radioactivity remaining decreased with time and the retention period was prolonged with a decrease in the water content of the hydrogels. The lower the water content of 125I-labeled gelatin hydrogels, the faster both the weight of the hydrogels and the gelatin radioactivity remaining decreased with time. The decrement profile of bFGF remaining in hydrogels was correlated with that of hydrogel weight and gelatin radioactivity, irrespective of the water content. Subcutaneous implantation of bFGF-incorporating gelatin hydrogels into the mice induced significant neovascularization. The retention period of neovascularization became longer as the water content of the hydrogels decreased. To study the decrease of activity of bFGF when implanted, bFGF-incorporating hydrogels were placed in diffusion chamber and implanted in the mouse subcutis for certain periods of time. When hydrogels explanted from the mice were again implanted, significant neovascularization was still observed, indicating that most of the biological activity of bFGF was retained in the hydrogels. It was concluded that, in our hydrogel system, biologically active bFGF was released as a result of in vivo degradation of the hydrogel. The release profile was controllable by changing the water content of hydrogels.     

Preparation, characterization, and in vitro enzymatic degradation of chitosan-gelatine hydrogel scaffolds as potential biomaterials

The crosslinking of chitosan (CHT) and gelatin (GEL) accomplished with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) was investigated and optimized in relation to hydrogels stability by varying the CHT/GEL mass ratio and the EDC/NHS molar ratio at different and constant EDC concentrations. Hydrogels were also fabricated in the presence of α-tocopherol to assess the release mechanism of a lipophilic drug from a highly-hydrophilic CHT/GEL hydrogel network. Alterations in the physico-chemical properties of hydrogels were characterized by differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR), and their biostability was studied within a simulated body-fluid solution (PBS of pH 7.4) at 37 °C for 24 h by evaluating the degree of swelling, followed by topography and morphology characterization using scanning electron microscopy (SEM). The analysis confirmed the formation of a modulated hydrogels porosity using different freezing temperatures prior to lyophilization. The in vitro degradation behaviors of the hydrogels were investigated for up to 5 weeks using collagenase, lysozyme, and N-acetyl-β-D-glucosaminidase by monitoring the weight-losses of hydrogels and their degradation products, being identified by UV-Vis spectroscopy and high-performance liquid chromatography (HPLC) as well as the pH monitoring of degraded solutions. It was observed that an inner morphological hydrogel structure influences their swelling and degradation behavior, which is additionally reduced by in-gel-embedded α-tocopherol because of hydrophobic interactions with their constituents, and hindering the effect on collagenase activity.     

Synthesis, properties and controlled release behaviors of hydrogel networks using cyclodextrin as pendant groups

Based on inclusion character of beta-cyclodextrin (beta-CD) with drug molecule and low glass transition temperature of poly(2-hydroxyethyl acrylate) (PHEA), a series of hydrogels with different compositions were synthesized by the copolymerization of a monovinyl cyclodexrin monomer with 2-hydroxyethyl acrylate (HEA). The structure and properties of the hydrogels were characterized by FTIR, DSC, TGA and swelling measurements. It is found that swelling ratios of these beta-CD hydrogels can keep a relative stability in the range of pH from 1.4 to 7.4, and are not sensitive to change in NaCl concentration. Using drug N-acety-5-methoxytryptamine (melatonin, MEL) as a model molecule, the controlled drug release behaviors of these hydrogels were investigated. The results indicate that the diffusion and permeation of MEL from the hydrogels may be a dominant factor for its release. Owing to the formation of MEL/beta-CD retarding diffusion rate of MEL, a sustained release of MEL from hydrogel with high content of beta-CD can be obtained compared with hydrogel PHEA without beta-CD.     

Derivation of epithelial-like cells from eyelid fat-derived stem cells in thermosensitive hydrogel

Injectable hydrogel is one of the great interests for tissue engineering and cell encapsulation. In the study, the thermosensitive chitosan/gelatin/β-glycerol phosphate (C/G/GP) disodium salt hydrogels were designed and investigated by different analyses. The eye fat-derived stem cells were used to evaluate the biocompatibility of hydrogels based on their phenotypic profile, viability, proliferation, and attachment ability. The results show that the sol/gel transition temperature of the C/G/GP hydrogel was in the range of 31.1–33.8?°C at neutral pH value, the gelation time was shortened, and the gel strength also improved at body temperature when compared with the C/GP hydrogel. In vitro cell culture experiments with eyelid fat-derived stem cells in hydrogel showed beneficial effects on the cell phenotypic morphology, proliferation, and differentiation. Microscopic figures showed that the eyelid fat stem cell were firmly anchored to the substrates and were able to retain a normal stem cell phenotype. Immunocytochemistry (ICC) and real-time–PCR results revealed change in the expression profile of eyelid fat stem cells grown with hydrogels when compared to those grown on control in epithelial induction condition. This study indicates that using chitosan/gelatin/β-glycerol phosphate hydrogel for cell culture is feasible and may apply in minimal invasive surgery in the future.     

Biodegradable poly(ethylene glycol) hydrogels crosslinked with genipin for tissue engineering applications

In this study amino-terminated poly(ethylene glycol) (PEG-diamine) hydrogels were crosslinked with genipin, a chemical naturally derived from the gardenia fruit. Dissolution, swelling, and PEG-genipin release properties were determined. The dissolution studies indicated that the hydrogels are water soluble, and that the dissolution rate was concentration, mass, and temperature dependent. The dissolution rates are easily tailored from 3 min to >100 days. The PEG-genipin release study indicated that the greatest release occurs within the first 24 h of immersion in water, and that incubation at 37 degrees C elicits a greater initial release than samples incubated at room temperature for all genipin concentrations. Through scanning electron microscopy it was observed that the hydrogels are porous, and surface morphology changes before and after swelling. Furthermore, smooth muscle cell (SMC) adhesion studies indicated that the PEG-genipin hydrogel is a suitable substrate for SMC seeding. Overall, the results of these studies indicate that PEG-genipin hydrogels may provide potential scaffolding for a variety of tissue engineering applications.     

Poly(vinyl alcohol)/collagen/hydroxyapatite hydrogel: Properties and in vitro cellular response

The objective of this study was to develop "bone-like" poly(vinyl alcohol) (PVA)/hydroxyapatite (HA)/type I collagen (Col) hydrogel composites that stimulate adhesion, proliferation, and differentiation of osteoblastic cells. The hydrogel composites were prepared by mixing PVA with nanoscale HA and Col using a physical mixing method. The concentration of the components was optimized during formulation development. PVA/Col/HA hydrogels were characterized for viscoelasticity, degree of swelling, mechanical strength, embedded erythromycin drug release, and cellular response of both osteoblastic MC3T3 cells and RAW 264.7 macrophage cells. Compressive strength tests confirmed that the PVA coating possessed greater elasticity and was mechanically enhanced by the freeze-thaw treatment. PVA/Col/HA gel is biocompatible and nontoxic to MC3T3 preosteoblasts, and the reinforcement from HA and Col reduced the inflammatory response from macrophages. Our findings demonstrate that PVA composites are biocompatible, and enhance cell adhesion, proliferation, and differentiation in vitro. We propose that PVA/Col/HA hydrogels represent one of the promising implant surface coating matrices for the improvement of implant osseointegration. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3071-3079, 2012.