Synthesis and characterization of glucosamine modified poly(ethylene glycol) hydrogels via photopolymerization

This study presented the synthesis and characterization of glucosamine (GlcN) modified poly (ethylene glycol) (PEG) hydrogels. The chemical structure was characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (¹H NMR) spectroscopy. The morphology of hydrogels was observed by scanning electron microscopy (SEM). The results indicated that GlcN was successfully incorporated into PEG hydrogel network. Moreover, the data of the swelling ratio showed that the ratio of GlcN‐modified PEG hydrogels was lower than that of pure poly(ethylene glycol) diacrylated (PEGDA). Biocompatibility of unreacted GlcN monomer and GlcN‐modified hydrogels was also evaluated in vitro. Compared with glucosamine hydrochloride, 2 and 5 mM N‐acroloyl‐glucosamine monomer exhibited no toxicity against bone marrow stromal cells (BMSCs), while with the concentration increased to 10 mM, cell viability appeared to decrease. However, when BMSCs were encapsulated in GlcN‐modified hydrogels via photopolymerization method, cells remained vigorous viability. Metabolic activity of the encapsulated cells demonstrated GlcN‐modified hydrogels was favorable for cell proliferation. Compared with free GlcN, covalent binding GlcN showed lower cytotoxicity and higher cell proliferation properties. As a result, GlcN‐modified PEGDA hydrogels could be used as safe and injectable cell carriers for in situ tissue engineering applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis and characterization of new injectable and degradable dextran-based hydrogels

Injectable and degradable hydrogels are very interesting networks for drug delivery and cell transplantation applications since they can be administered in the human body in a minimally invasive way. In most cases, the crosslinking reaction occurs by photopolymerisation or free radical polymerisation; however, the use of chemical initiators may promote cell death. In the current work, injectable and degradable dextran-based hydrogels were prepared without the use of initiators. Dextran, a natural glucose-containing polysaccharide, was oxidized with sodium periodate (dexOx) and the derivatives characterized by NMR and FTIR spectroscopy's as well as by colorimetric techniques. The oxidized derivatives were crosslinked with adipic acid dihydrazide (AAD), forming a gel within 2-4 min. The obtained hydrogels were characterized by their mechanical properties, swelling and degradation behavior under physiologic conditions. In addition, the hydrogel interior morphology as well as porous structure was evaluated by scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP). MIP analysis showed that dexOx hydrogels crosslinked with 10% of AAD were macroporous with pore sizes ranging from 0.32 to 0.08 μm. As expected, the average pore size increased during hydrogel degradation as confirmed by SEM and MIP studies.     

Gelatin Methacryloyl–Riboflavin (GelMA–RF) Hydrogels for Bone Regeneration

Gelatin methacryloyl (GelMA) is a versatile biomaterial that has been used in various biomedical fields. UV light is commonly used to photocrosslink such materials; however, its use has raised several biosafety concerns. We investigated the mechanical and biological properties of a visible-wavelength (VW)-light-crosslinked gelatin-based hydrogel to evaluate its viability as a scaffold for bone regeneration in bone-destructive disease treatment. Irgacure2959 or riboflavin was added as a photoinitiator to create GelMA solutions. GelMA solutions were poured into a mold and exposed to either UV or VW light. KUSA-A1 cell-laden GelMA hydrogels were crosslinked and then cultured. Mechanical characterization revealed that the stiffness range of GelMA–RF hydrogel was suitable for osteoblast differentiation. KUSA-A1 cells encapsulated in GelMA hydrogels photopolymerized with VW light displayed significantly higher cell viability than cells encapsulated in hydrogels photopolymerized with UV light. We also show that the expression of osteogenesis-related genes at a late stage of osteoblast differentiation in osteoblasts encapsulated in GelMA–RF hydrogel was markedly increased under osteoblast differentiation-inducing conditions. The GelMA–RF hydrogel served as an excellent scaffold for the encapsulation of osteoblasts. GelMA–RF hydrogel-encapsulated osteoblasts have the potential not only to help regenerate bone mass but also to treat complex bone defects associated with bone-destructive diseases such as periodontitis.     

Swelling and Diffusion Properties of Poly(acrylamide-co-maleic acid) Hydrogels: A Study with Different Crosslinking Agents

Crosslinked hydrogels comprising acrylamide (AAm) and maleic acid (MA) were synthesized by free radical polymerization in presence of a crosslinker using ammonium persulfate (APS) and N,N,N¹,N¹-tetramethylethylenediamine (TMEDA) as initiator and activator, respectively. The crosslinked hydrogel formation was confirmed by IR analysis. The swelling/de-swelling characteristics were studied in detail for crosslinked poly(acrylamide-co-maleic acid) [poly(AAM-co-MA)] hydrogels containing different amounts of maleic acid. Four different crosslinkers such as 1,2-ethyleneglycol dimethacrylate (EGDMA), 1,4-butanediol diacrylate (BDDA), 1,6-hexanediol diacrylate (HDDA), and diallyl phthalate (DP) were utilized to study their influence on the swelling behavior of the hydrogels. The effect of reaction parameters such as the concentration of crosslinker and initiator on swelling capacity of the crosslinked poly(AAm-co-MA) hydrogels was also investigated. Further, the influence of various salts, simulated biological fluids, and pH solutions on the swelling pattern of hydrogels was studied extensively. Phase separation morphology of crosslinked hydrogels was also studied by differential scanning calorimetry. The morphology of crosslinked hydrogels were revealed using scanning electron microscopy (SEM).     

Fabrication,swelling behavior,and water absorption kinetics of genipin-crosslinked gelatin–chitosan hydrogels

Gelatin/chitosan hydrogels have attracted considerable attention over the last 2 decades in various fields of applications. In this paper, chemically crosslinked composite hydrogels with different gelatin-to-chitosan weight ratios were fabricated and crosslinked with different amounts of genipin via the solvent casting technique combined with freeze-drying. Fourier-transform infrared, scanning electron microscopy (SEM), liquid displacement method, and gravimetric analysis were used to examine the chemical, microstructural, and physical properties of the hydrogels. IR spectra confirmed the formation of covalent bonds between the amino groups of the parent's macromolecules and genipin. SEM micrographs indicated that the hydrogels possessed a highly porous structure with well-defined pore geometries. The swelling capacity and degradation rate of the specimens reduced with increasing the amounts of chitosan and/or genipin. In-depth swelling measurements revealed that the first-order kinetic model was only applicable in the early stage of the swelling study; however, the water absorption behavior of the hydrogels was best described by the pseudo-second-order kinetic model (Schott's model) throughout the swelling experiment. The genipin-crosslinked hydrogels were found to support MC3T3-E1 cell proliferation. The results of this paper thus suggest the 1.5% genipin-crosslinked gelatin/chitosan hydrogels as promising candidates for on-demand drug delivery applications or more precisely osteoarthritis drug delivery systems.     

In situ formation of thermosensitive P(NIPAAm-co-GMA)/PEI hydrogels

A strategy for in situ chemical gelation of poly(N-isopropylacrylamide-co-glycidyl methacrylate)/polyethylenimine (P(NIPAAm-co-GMA)/PEI) polymers has been demonstrated. Two kinds of P(NIPAAm-co-GMA) with epoxy pendant groups were prepared. When the solution of P(NIPAAm-co-GMA) was mixed with branched polyethylenimine (PEI, M_w 800), the cross-linking between the epoxy functional groups and amines, a type of nucleophilic substitution reaction occurred. The corresponding gelation process was confirmed via rheology. The in situ formed hydrogels were studied via scanning electric microscopy (SEM) and the equilibrium swelling ratio, swelling kinetics, and temperature response kinetics were examined. The strategy described here presents a potential alternative to the traditional synthesis techniques for the in situ formation of thermosensitive hydrogels.     

微结构葡聚糖凝胶浓缩分离蛋白质的性能

采用UV,HPLC等测试方法研究了含微结构的葡聚糖凝胶（BHMs）对蛋白的浓缩分离性能。结果表明：含微结构的葡聚糖凝胶在室温下对牛血清蛋白的浓缩分离效率达95.3%以上,随温度的升高,浓缩分离效率降低,且当温度超过BHMs凝胶的低临界溶液温度(40℃)后,浓缩分离效率发生突变;和普通交联葡聚糖凝胶相比,通过控制流动相的温度,葡聚糖BHMs凝胶可实现对多种不同分子量蛋白的高效分离,提高了分离效率,分离时间由24h缩短至9h。吸水溶胀动力学以及SEM分析表明,BHMs凝胶的溶胀满足指数动力学方程,疏松多孔性结构及由其决定的温度敏感性是BHMs凝胶具备良好浓缩分离性能的原因。     

Synthesis and characterization of in situ cross-linked hydrogel based on self-assembly of thiol-modified chitosan with PEG diacrylate using Michael type addition

A novel injectable in situ cross-linked hydrogel has been designed via Michael type addition between thiol-modified chitosan (CS-NAC) and PEG diacrylate (PEGDA). Hydrogel was rapidly formed in situ under physiological conditions. The gelation time depended on the content of free thiols in CS-NAC, temperature, and concentration of CS-NAC and PEGDA. Thermogravimetric analysis showed the thermal stabilities of hydrogels. SEM observation results confirmed a porous 3D structure. Rheological studies showed that the cross-linking density and elasticity of hydrogel had a correlation to the content of CS-NAC and PEGDA. Swelling studies revealed that these hydrogels had a high initial swelling and were degradable under physiological conditions. And swelling was highly temperature-dependent and was directly related to the amount of cross-linking. Biological activities of the hydrogels were evaluated by in vitro cell compatibility on HDFs and A549 cells and the results indicated that the hydrogel was biocompatible.     

A novel injectable and in situ crosslinked hydrogel based on hyaluronic acid and α,β-polyaspartylhydrazide

A new injectable and in situ crosslinked hydrogel, based on a hyaluronic acid (HA) derivative and α,β-polyaspartylhydrazide (PAHy), was produced during the research. This biodegradable and high molecular weight hydrogel can be in situ crosslinked in 15 s by the condensation reaction between aldehyde and amine groups. The HA derivative carrying aldehyde (HAALD) was oxidized from HA by sodium periodate, while the synthesis of hydrogel was performed in a phosphate-buffered saline solution (PBS) using HAALD and PAHy without addition of crosslinker or catalyst. The pH and concentration of the reaction solution, considered as the important factors of the amine-aldehyde reaction, were changed to reveal the crosslinking rule. Thereafter, crosslinked hydrogels were characterized by gelation time, gel content, swelling ratio, and in vitro degradation. Furthermore, the modified polymers were characterized by Fourier transformed infrared (FTIR) spectroscopy to examine their structures. Results from scanning electron microscope (SEM) observations confirmed that a freeze-dried sample revealed a porous hydrogel structure with interconnected pores. The measurement of the cell adhesion confirmed the application potential of HAALD-PAHy hydrogels. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.     

Point‐bonded electrospun polystyrene fibrous mats fabricated via the addition of poly(butylacrylate) adhesive

Because of poor mechanical strength, applications of electrospun polystyrene (PS) fibrous mats are quite limited. The introduction of various concentrations of poly (butylacrylate) adhesives (PBAs) into PS solutions led to the fabrication of point‐bonded electrospun PS fibrous mats with good mechanical strength. The morphologies of PS/PBA fibers with varying PBA content (0?50 wt%) were investigated using scanning electron microscopy (SEM), and the results were compared with pure PS and PBA fibers fabricated with various solvents. SEM images indicated that point‐bonded PS/PBA fibers were uniformly distributed with an average diameter of 1–2 μm. On increasing concentration of PBA up to 20 wt%, porous PS/PBA fibrous mats were obtained. However, solid films were formed at very high concentrations of PBA. The Young's modulus and tensile strength of PS/PBA fibrous mats increased up to 52.4 and 2.7 MPa, respectively. The resultant enhancement of the mechanical properties of PS fibrous mats on addition of PBA increases the number of potential applications of these materials. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers     

Investigation of polyvinyl alcohol nanocomposite hydrogels containing chitosan nanoparticles as wound dressing

Polymeric hydrogels, water-swollen 3?D networks of the polymers, have found wide ranges of applications in the medical fields, such as wound care and wound dressing, in order to prevent infections. Prevention from microorganisms transfer in to the wounds is one of the ideal wound dressing duties of polyvinyl alcohol (PVA) hydrogels. In this study, at the start, under optimal conditions, nanoparticles of chitosan using ionotropic gelation method were synthesized and in the next step in order to achieve particles with a minimum size, they were evaluated by scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). Then after to obtain a wound dressing with preferable properties, nanocomposite hydrogels using a combination of PVA and 5, 10 and 15?wt% chitosan nanoparticles were prepared through freezing-thawing cycles. The necessary features of PVA nanocomposite hydrogels for wound dressing were investigated. The dispersion state of nanoparticles and structure of samples were evaluated by SEM microscopy. The nanoparticle size and the nanoparticle size distribution of chitosan was determined using the dynamic light scattering test at the nanometer scale. The physical behavior of hydrogels such as swelling and gel fraction was studied and their mechanical properties were investigated by compressive test. Finally the antimicrobial test and biocompatibility as cell viability were carried out. The results proved that the PVA nanocomposite hydrogels fulfill the requirements of a good wound dressing with desirable characteristics such as favorable swelling and acceptable strength, excellent barrier against microbial penetration.     

Injectable Human Hair Keratin–Fibrinogen Hydrogels for Engineering 3D Microenvironments to Accelerate Oral Tissue Regeneration

Traumatic injury of the oral cavity is atypical and often accompanied by uncontrolled bleeding and inflammation. Injectable hydrogels have been considered to be promising candidates for the treatment of oral injuries because of their simple formulation, minimally invasive application technique, and site-specific delivery. Fibrinogen-based hydrogels have been widely explored as effective materials for wound healing in tissue engineering due to their uniqueness. Recently, an injectable foam has taken the spotlight. However, the fibrin component of this biomaterial is relatively stiff. To address these challenges, we created keratin-conjugated fibrinogen (KRT-FIB). This study aimed to develop a novel keratin biomaterial and assess cell–biomaterial interactions. Consequently, a novel injectable KRT-FIB hydrogel was optimized through rheological measurements, and its injection performance, swelling behavior, and surface morphology were investigated. We observed an excellent cell viability, proliferation, and migration/cell–cell interaction, indicating that the novel KRT-FIB-injectable hydrogel is a promising platform for oral tissue regeneration with a high clinical applicability.     

A Carbodiimide Coupling Approach for PEGylating GelMA and Further Tuning GelMA Composite Properties

To date the low mechanical strength and high swelling rate of gelatin-based products have limited their use toward many tissue engineering targets. Here a new approach to tuning methacrylated gelatin (GelMA) properties involving the carbodiimide coupling of polyethylene glycol (PEG) to the GelMA molecule is investigated. PEGylation improves the capacity of the solution to flow and reduces hydrogel swelling, while in composite form with nano-hydroxyapatite (nHA) particles there is no impact on swelling. Differential scanning calorimetry (DSC) reveals that PEGylation likely restores some of the triple helical nature of gelatin to the GelMA and increases steric hindrance. Furthermore, triethyleneglycol dimethacrylate inclusion in GelMA-PEG composites is able to address the loss in dynamic stiffness reported as a result of PEGylation. Altogether PEGylated GelMA shows evidence of reduced interaction with water compared to control GelMA, whether alone or in composite form. By tuning this interaction and reducing the volume of water necessary to solvate GelMA, the potential to use GelMA composites for a variety of tissue engineering applications is greatly improved.     

Frontal polymerization preparation of poly(acrylamide‐co‐acrylic acid)/activated carbon composite hydrogels for dye removal

A series of poly(acrylic acid‐co‐acrylamide) (PAA)/activated carbon (AC) composite hydrogels were rapidly prepared via frontal polymerization (FP). It was found that an increase in the concentration of AC caused an increase in the front velocity (V_f) and the highest front temperature (T_max). It may be attributed to that AC particles could increase the liquid viscosity of reaction mixture and remain the reaction heat during FP. The Fourier transform infrared and scanning electron microscopy (SEM) confirmed that AC particles had entered the hydrogel network, and many spherical AC particles with an average diameter of 0.5–1 μm had been dispersed homogeneously in the PAA hydrogel matrix. The swelling behavior showed that the equilibrium swelling values of hydrogels increased when the concentration of AC particles increased. Adsorption studies showed that incorporation of AC particles into PAA hydrogel matrix could increase the sites of interaction between the hydrogels and crystal violet molecules and result in an increase of adsorption capacities of hydrogels toward dyes. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Hydroxyapatite-Integrated,Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.     

半纤维素/碳纳米管复合凝胶的溶胀性能

采用 (NH4)2S2O8-Na2SO3为引发剂体系,N,N-亚甲基双丙烯酰胺（BIS）为交联剂,利用自由基聚合法成功制备了半纤维素/碳纳米管复合凝胶。用SEM对凝胶的结构形态进行了研究分析;研究了单体比例、碳纳米管含量和pH值对凝胶溶胀率的影响;并应用溶胀动力学方程对试验数据进行拟合。研究结果表明：半纤维素/碳纳米管复合凝胶的溶胀率随着甲基丙烯酸/半纤维素比例的增加而减小,随着碳纳米管含量的增加而减小;pH≤11时随pH值的增加而增大,pH>11时随pH值的增加而减小。拟合结果表明整个溶胀过程符合Schott二级动力学模型。     

Fabrication and characterization of novel macroporous cellulose–alginate hydrogels

Novel macroporous hydrogels were prepared by blending of cellulose and sodium alginate (SA) solution, and then cross-linking with epichlorohydrin. The resulting cellulose/SA hydrogels were characterized by solid-state ¹³C NMR, wide-angle X-ray diffraction (WXRD), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), rheological measurement, dynamic mechanical analysis (DMA) and swelling test to evaluate their structure, interior morphology, gelation time, compressive modulus, and equilibrium swelling ratio. Our findings revealed that the cellulose acted as backbone in the hydrogels, whereas SA contributed to the higher equilibrium swelling ratio. The combination of cellulose having semi-stiff chains and SA containing –COOH groups in the cross-linking hydrogel created the macroporous structure. This work provided a new pathway for preparation of hydrogel with large porous structure through incorporation of stiff polymer as support of pore wall and acidic polysaccharide as expander of pore size because of high water-absorbency.     

Process study,development and degradation behavior of different size scale electrospun poly(caprolactone) and poly(lactic acid) fibers

This study describes the preparation of electrospun poly(caprolactone) (PCL) and poly(lactic acid) (PLA) fibrous scaffolds with and without nano-hydroxyapatite (nHAp) having nanoscale, microscale and combined micro/nano (multiscale) architecture. Processing parameters such as polymer concentration, voltage, flow rate and solvent compositions were varied in wide range to display the effect of each one in determining the diameter and morphology of fibers. The effect of each regulating parameter on fiber morphology and diameter was evaluated and characterized using scanning electron microscope (SEM). Degradability of the selected fibrous scaffolds was verified by phosphate buffered saline immersion and its morphology was analyzed through SEM, after 5 and 12 months. Quantitative measurement in degradation was further evaluated through pH analysis of the medium. Both studies revealed that PLA had faster degradation compared to PCL irrespective of the size scale nature of fibers. Structural stability evaluation of the degraded fibers in comparison with pristine fibers by thermogravimetric analysis further confirmed faster degradability of PLA compared to PCL fibers. The results indicate that PLA showed faster degradation than PCL irrespective of the size-scale nature of fibrous scaffolds, and therefore, could be applied in a variety of biomedical applications including tissue engineering.     

Humic acid embedded chitosan/poly (vinyl alcohol) pH-sensitive hydrogel: Synthesis,characterization, swelling kinetic and diffusion coefficient

In the present research, humic acid (HA) embedded chitosan (CHT)-poly (vinyl alcohol) (PVA) pH-sensitive hydrogels have been synthesized using glutaraldehyde as a crosslinker. The hydrogels were characterized by Fourier-transform infrared (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis. The effect of HA content, pH, and temperature on the equilibrium solvent uptake has been investigated. With higher HA contents, the equilibrium swelling capacity increases while lower concentrations of acid cause a decrease in the degree of the swelling. The hydrogels have been found to undergo a number of swelling/deswelling cycles when pH of the swelling medium changes from 1.5 to 11.0. Fick’s law, first-order, and second-order kinetic models were applied to the swelling ratio of hydrogels to explain the mass transfer mechanism and specify swelling kinetic parameters. The swelling parameters such as equilibrium swelling capacity, swelling rate constant, swelling exponent, initial swelling rate, diffusion coefficient, etc., have been evaluated.