The controlled release behavior and pH‐ and thermo‐sensitivity of alginate/poly(vinyl alcohol) blended hydrogels

Poly(vinyl alcohol) (PVA) was blended with sodium alginate (Alg) in various ratios and crosslinked with calcium chloride and made into hydrogel membranes. The dependence of the swelling behavior of these Alg‐Ca/PVA hydrogels on pH was investigated. The temperature‐dependent swelling behavior of the semi‐interpenetrating network (semi‐IPN) hydrogels was examined at temperatures from 2 to 45°C and the enthalpy of mixing (ΔH_mix) was determined at various temperatures. The molecular structure of the hydrogels was studied by infrared spectroscopy and their water structure in the semi‐IPN hydrogels was measured by differential scanning calorimetry (DSC). The influence of Ca²⁺ content on the network structure of Alg‐Ca/PVA hydrogels was investigated in terms of the compressive elastic modulus, effective crosslinking density, and the polymer–solvent interaction parameter based on the Flory theory. The loading of alizarin red S (ARS) followed the Langmuir isotherm mechanism and the release kinetics of ARS from the Alg‐Ca/PVA hydrogels followed the Fickian diffusion mechanism. Copyright © 2008 John Wiley & Sons, Ltd.     

Photocrosslinked methacrylated poly(vinyl alcohol)/hydroxyapatite nanocomposite hydrogels with enhanced mechanical strength and cell adhesion

Poly(vinyl alcohol) (PVA) hydrogels with high water content, good load‐bearing property, low frictional behavior as well as excellent biocompatibility have been considered as promising cartilage replacement materials. However, the lack of sufficient mechanical properties and cell adhesion are two critical barriers for their application as cartilage substitutes. To address these problems, herein, methacrylated PVA with low degree of substitution of methacryloyl group has been synthesized first. Then, methacrylated PVA‐glycidyl methacrylate/hydroxyapatite (PVA‐GMA/Hap) nanocomposite hydrogels have been developed by the photopolymerization approach subsequently. Markedly, both pure PVA‐GMA hydrogel and PVA‐GMA/Hap nanocomposite hydrogels exhibit excellent performance in compressive tests, and they are undamaged during compressive stress–strain tests. Moreover, compared to pure PVA‐GMA hydrogels, 8.5‐fold, 7.4‐fold, and 14.2‐fold increase in fracture stress, Young's modulus and toughness, respectively, can be obtained for PVA‐GMA/Hap nanocomposite hydrogels with 10 wt % Hap nanoparticles. These enhancements can be ascribed to the intrinsic property of PVA‐GMA and strong hydrogen bonding interactions between PVA‐GMA chain and Hap nanoparticles. More interestingly, significant improvement in the cell adhesion can also be successfully achieved by incorporation of Hap nanoparticles. These biocompatible nanocomposite hydrogels have great potential to be used as cartilage substitutes. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1882–1889     

不同条件下合成的纳米羟基磷灰石晶体的性能研究

用磷酸钠和硝酸钙为原料,在8种不同条件下制备了纳米羟基磷灰石(n-HA)晶体,研究了不同条件下制备的n-HA晶体的形态、组成、Ca/P摩尔比和结晶度。运用透射电镜((TEM)、红外光谱(IR)和X射线衍射(XRD)分析和表征了不同条件下得到的纳米羟基磷石灰晶体的形貌、组成和结晶度。用化学方法分析了纳米羟基磷灰石晶体的Ca/P摩尔比。结果表明,不同条件下合成的纳米磷灰石晶体均为含有HPO42-和CO32-的弱结晶结构,与自然骨磷灰石类似。     

Composite hydrogels based on polyacrylamide and cellulose: Synthesis and functional properties

Biocompatible composite hydrogels based on polyacrylamide and reinforced with bacterial or vegetable cellulose were synthesized. In the mechanical characteristics and water content, these hydrogels are similar to knee joint cartilages with average rigidity level. The structure and chemical composition of the hydrogels after their residence for 45 days in laboratory animal joints were studied by scanning electron microscopy and energydispersive X-ray microanalysis. Prolonged contact of the hydrogels with bones results in formation of calcium phosphate spherulites similar in composition to hydroxyapatite.     

The effect of morphological changes on the coprecipitation of strontium by calcium phosphate

The coprecipitation of strontium by a calcium phosphate phase formed at an elevated pH 10.8 was investigated. The first phase obtained under these conditions in the amorphous calcium phosphate (ACP) which is transformed into crystalline hydroxyapatite (HA) after the induction period. Is has been shown that this transformation together with morphological changes of the precipitated solid phase, influences the amount of the sorbed strontium significantly. The possible consequences of this finding on practical application of coprecipitation of strontium by calcium phosphate have been discussed.     

Quartz Crystal Microbalance Analysis of DNA-Templated Calcium Phosphate Mineralization

A quartz crystal microbalance (QCM) sensor was developed for the quantitation of calcium phosphate mineralization and the assessment of DNA as a template molecule. Inherent advantages of QCM, such as nanogram sensitivity, temporal resolution, surface-based measurements, and flow capabilities, were leveraged in the design of this sensor, and in-line fluidic mixing was used to control precursor reaction. This research shows that DNA, a highly programmable anionic polymer, is able to template and control mineralization of calcium phosphate, with nucleation occurring in less than 15 min and initial rates ranging from 4 to 8 ng/min. FT-IR measurements show mineralized material to be calcium phosphate resembling hydroxyapatite (HAP) when a DNA template is used. DNA is a promising mineralization template, and the QCM proves to be a dynamic technique for a broad range of heterogeneous mineralization experiments in complement to classic, diffusion-limited, end-point analysis techniques.     

Swelling and biocompatibility of sodium alginate/poly(γ‐glutamic acid) hydrogels

Sodium alginate (Alg) hydrogel films were crosslinked with either calcium poly(γ‐glutamate) (Ca‐PGA) or CaCl₂. The hydrophilicity of the resulting hydrogel films was evaluated through swelling tests, water retention capacity tests, and water vapor permeation tests. The swelling ratio, water retention capacity, and the water vapor transmission rate (WVTR) of Alg/Ca‐PGA were higher than those of Ca‐Alg. The swelling ratio of Alg/Ca‐PGA was 651 and 190% at pH 7.4 and pH 1.2, respectively. The tensile strength of Alg/Ca‐PGA hydrogel was lower than that of Ca‐Alg. The results of hemocompatibility test showed that Alg/Ca‐PGA caused shorter activated partial thromboplastin time (APTT) than Ca‐Alg. Both Ca‐Alg and Alg/Ca‐PGA exhibited almost no adsorption of human serum albumin (HSA), whereas the adsorption of human plasma fibrinogen (HPF) of Ca‐Alg was 10 times of that of Alg/Ca‐PGA. In addition, Alg/Ca‐PGA exhibited platelet adhesion higher than Ca‐Alg. Furthermore, both Alg/Ca‐PGA and Ca‐Alg exhibited no cytotoxicity. Copyright © 2009 John Wiley & Sons, Ltd.     

Calcium phosphate mineralization with linear poly(ethylene imine): a time-resolved study

We have earlier shown that linear poly(ethylene imine) (LPEI) is an efficient growth modifier for calcium phosphate mineralization from aqueous solution (Shkilnyy et al., Langmuir, 2008, 24 (5), 2102). The current study addresses the growth process and the reason why LPEI is such an effective additive. To that end, the solution pH and the calcium and phosphate concentrations were monitored vs. reaction time using potentiometric, complexometric, and photometric methods. The phase transformations in the precipitates and particle morphogenesis were analyzed by X-ray diffraction and transmission electron microscopy, respectively. All measurements reveal steep decreases of the pH, calcium, and phosphate concentrations along with a rapid precipitation of brushite nanoparticles early on in the reaction. Brushite transforms into hydroxyapatite (HAP) within the first 2 h, which is much faster than what is reported, for example, for calcium phosphate precipitated with poly(acrylic acid). We propose that poly(ethylene imine) acts as a proton acceptor (weak buffer), which accelerates the transformation from brushite to HAP by taking up the protons that are released from the calcium phosphate precipitate during the phase transformation.     

Impact of the Type of Crosslinking Agents on the Properties of Modified Sodium Alginate/Poly(vinyl Alcohol) Hydrogels

Here, we report on studies on the influence of different crosslinking methods (ionic and chemical) on the physicochemical (swelling ability and degradation in simulated body fluids), structural (FT-IR spectra analysis) and morphological (SEM analysis) properties of SA/PVA hydrogels containing active substances of natural origin. First, an aqueous extract of Echinacea purpurea was prepared using a Soxhlet apparatus. Next, a series of modified SA/PVA-based hydrogels were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate (PEGDA, M_n = 700 g/mol) as a crosslinking agent and, additionally, the ionic reaction in the presence of a 5% w/v calcium chloride solution. The compositions of SA/PVA/E. purpurea-based hydrogels contained a polymer of natural origin—sodium alginate (SA, 1.5% solution)—and a synthetic polymer—poly(vinyl alcohol) (PVA, M_n = 72,000 g/mol, 10% solution)—in the ratio 2:1, and different amounts of the aqueous extract of E. purpurea—5, 10, 15 or 20% (v/v). Additionally, the release behavior of echinacoside from the polymeric matrix was evaluated in phosphate-buffered saline (PBS) at 37 °C. The results indicate that the type of the crosslinking method has a direct impact on the release profile. Consequently, it is possible to design a system that delivers an active substance in a way that depends on the application.     

聚(L-谷氨酸)水凝胶介导羟基磷灰石的生物矿化

以1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC·HCl)为羧基活化剂, 己二酸二酰肼(ADH)为交联剂, 制备了生物活性聚(L-谷氨酸)(PLGA)水凝胶. 通过X射线衍射和扫描电子显微镜等表征了在不同浓度模拟体液(SBF)中羟基磷灰石(HA)的形成和生长. PLGA水凝胶的表面和内部均可观察到HA的形成和生长. 同时探讨了PLGA水凝胶矿化前后的力学性能. 将矿化前后PLGA水凝胶用于脂肪干细胞(ASCs)的培养, 研究其细胞相容性.     

Synthesis of pH‐responsive photocrosslinked hyaluronic acid‐based hydrogels for drug delivery

Photocrosslinked hyaluronic acid/poly(vinyl alcohol)‐styrylpyridinium (HA/PVA‐SbQ) hydrogels were synthesized for controlled antitumor drug delivery. The photocrosslinking reaction was rapid, and the time required for completely converting into the insoluble hydrogels was less than 500 s on exposure to 5 mW/cm² UV light irradiation. The resulting hydrogels exhibited sensitivity to the pH value of the surrounding environment. Scanning electron microscopic analysis revealed that the morphology and the pore size of the hydrogels could be controlled by changing the ratio of HA and PVA‐SbQ in the formulations. Paclitaxel (PTX)‐loaded hydrogel could also be formed rapidly by UV irradiation of a mixed solution of HA/PVA‐SbQ and PTX. Release profiles of PTX from the hydrogels showed pH‐dependent and sustained manner. Moreover, our data revealed that PTX released from the HA hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of HA hydrogels without PTX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using HA‐based hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

Development of temperature-responsive semi-IPN hydrogels from PVA-PNVC-PAm for controlled release of anti-cancer agent

A series of semi-interpenetrating polymeric network (semi-IPN) hydrogels were synthesized using poly(vinyl alcohol) (PVA), monomers N-vinylcaprolactam (NVC) acrylamide (Am), and cross-linker bis[2-methacryloyloxy] ethyl phosphate (BMEP). The hydrogels were synthesized by using free-radical polymerization using ammonium persulphate (APS) as an initiator at 60°C. The hydrogels were characterized by various techniques such as Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to confirm the formation, crystallinity, and morphological behavior. The swelling behavior at various temperatures and pH conditions showed that the semi-IPN hydrogels were good candidates for temperature-responsive nature. 5-Flurouracil (FU), a model anticancer drug, was successfully encapsulated and the encapsulation efficiency was found in range of 50–74% for different hydrogels. Further, in-vitro release studies were performed to investigate the release mechanism. The cumulative release studies showed that the developed hydrogels are potentially efficient for the gastrointestinal drug delivery of FU.     

Effect of Calcium Precursors and pH on the Precipitation of Carbonated Hydroxyapatite

Three types of calcium precursors (nitrate, hydroxide and catbonate) were used in the synthesis of carbonated hydroxyapatite (cHA) using a precipitation method via a chemical reaction with di-ammonium hydrogen phosphate as the phosphate precursor. The precipitation method was chosen over many other methods due to its flexibility to changes in processing parameters to control the phases formed, the particle size, as well as, the morphology of the as-synthesized powders. The focus of the study was on cHA as it is deemed to mimic the composition of the human bone much closer as compared to the stoichiometric hydroxyapatite. When the chemical reaction was completed, the precipitate was dried, ground and characterized by x-ray diffraction (XRD), electron microscopy (both FESEM and TEM) and particle size analysis. Only the nitrate precursor produced a single-phase carbonated hydroxyapatite (cHA), whilst the other two precursors produced a secondary calcite phase or did not react fully. This is due to the low solubility of the calcium hydroxide and the incomplete reaction of the calcium carbonate. An increase in pH has been observed to lead to higher carbonate content in the synthesized cHA and a smaller crystallite size.     

Cryogenic Designing of Biocompatible Blends of Polyvinyl alcohol and Starch with Macroporous Architecture

The present paper discusses synthesis, characterization, and blood compatibility studies of macroporous cryogels of PVA and starch. Biocompatible spongy porous hydrogels of polyvinyl alcohol–starch have been synthesized by repeated freezing–thawing methods and characterized by Infra red (FTIR) and environmental scanning electron microscopy (ESEM) techniques, respectively, to gain insights for structural and morphological features. The FTIR analysis of prepared cryogels indicated that starch was introduced into the network of cryogel possibly via formation of hydrogen bonds between the PVA and starch clusters. The “cryogels” were evaluated for their water uptake potentials and influence of various factors such as chemical architecture of the spongy hydrogels, pH and temperature of the swelling bath were investigated on the degree of water sorption by the cryogels. The hydrogels were also swollen in salt solutions and various simulated biological fluids. The biocompatibility of the prepared cryogels was judged by in vitro methods of blood–clot formation viz. percent haemolysis and protein (BSA) adsorption. The cryogels were also studied for their pores morphology and percent porosity and the effect of chemical composition on the extent of porosity was also investigated.     

Chemotactic ion-releasing hydrogel for synergistic antibacterial and bone regeneration

The repair of critical-sized bone defects remains a major concern in clinical care. Herein, a multifunctional hydrogel is rationally designed to synergistically photothermal antibacterial and potentiate bone regeneration via adding magnesium oxide nanoparticle and black phosphorus nanosheet (BPNS) into poly(vinyl alcohol)/chitosan hydrogel (PVA/CS-MgO-BPNS). Under the dual effect of near-infrared irradiation and CS intrinsic antibacterial properties, PVA/CS-MgO-BPNS hydrogel can kill more than 99.9% of Staphylococcus aureus and Escherichia coli. The released Mg ions stimulate the migration of mesenchymal stem cells (MSCs) to hydrogels and synergize with released phosphate to promote osteogenic differentiation. The PVA/CS-MgO-BPNS hydrogel also promotes calcium phosphate particle formation and therefore improves the biomineralization ability. Furthermore, the potential molecular mechanism of PVA/CS-MgO-BPNS to regulate MSCs migration and differentiation is through activating phosphoinositide 3-kinase (PI3K)-Akt signaling pathways through RNA-seq analysis. Finally, the PVA/CS-MgO-BPNS hydrogel could significantly promote endogenous bone tissue regeneration in the rat skull defect model. Taken together, this easy fabricated multifunctional hydrogel has good clinical applicability for the repair of large-scale bone defects.     

Crosslinking of poly(vinyl alcohol) using functionalized gold nanoparticles

We report on the preparation of a new class of polymer hydrogels obtained through the chemical crosslinking reaction of poly(vinyl alcohol) (PVA) and functionalized gold nanoparticles. Carboxylic group functionalized gold nanoparticles were synthesized, dispersed in a PVA matrix and allow to react with the hydroxyl groups of PVA at high temperature. FT-IR and swelling experiments carried out on the cross-linked samples confirmed that the crosslinking reaction took place. This is the first time, to our knowledge, that functionalized nanoparticles are used as chemical crosslinking agents.     

Manufacturing of pH sensitive PVA/PVP/MWCNT and PVA/PEG/MWCNT nanocomposites: an approach for significant drug release

The purpose of this paper is studying the effect of incorporation of Multiwall Carbon Nanotubes (MWCNT) into two different nanocomposites in poly vinyl alcohol (PVA)/polyvinylpyrrolidone (PVP), and PVA/Polyethylene glycol (PEG). MWCNT were synthesized by chemical vapor deposition (CVD) method using acetylene and Fe/Co/Al₂O₃ as carbon precursor and catalyst, respectively. Nitric acid and sulfuric acid were used for purification and functionalization of MWCNT. Afterward, highly pure and functionalized MWCNT (0, 0.02, and 0.05% w/w) were incorporated in PVA/PVP and PVA/PEG to synthesize PVA/PVP/MWCNT and PVA/PEG/MWCNT nanocomposites hydrogel membranes that cross-linked by freezing–thawing. PEG and PVP were selected in these nanocomposites as dispersion matrix for MWCNT as well as for increasing the elasticity of the nanocomposites membranes. The morphology of the hydrogels was characterized by SEM, FTIR, XRD, TGA, and the mechanical properties of the hydrogel membranes were investigated. The swelling behavior in different pH-buffer solutions was studied as well as studying weight loss percentage and swelling kinetic. The drug releasing process of the hydrogel membranes was investigated using salicylic acid as a model drug. It was found that MWCNT are dispersed well into the polymers and crystallinity, mechanical properties and thermal stability of the hydrogels contain MWCNT are better than that without MWCNT. Maximum degree of swelling was observed at pH 7 and swelling degree increases with increasing the ratio of MWCNT in the hydrogels from 0.02 to 0.05%. All hydrogel membranes followed non-Fickian mechanism and drug releasing were controlled by varying the pH and amount of MWCNT.     

Application of sensitive hydrogels in chemical and pH sensors

In the present work, pH-sensitive poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) blends as well as hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm), which are sensitive to organic solvent concentration in aqueous solutions, were used in silicon micromachined sensors. A sensitivity of approximately 15 mV/pH was obtained for a pH sensor with a 50 μm thick PVA/PAA hydrogel layer in a pH range above the acid exponent of acrylic acid (pK_a=4.7). The output voltage versus pH-value characteristics and the long-term signal stability of hydrogel-based sensors were investigated and the measurement conditions necessary for high signal reproducibility were determined. The influence of the preparation conditions of the hydrogel films on the sensitivity and response time of the chemical and pH sensors is discussed.     

Effect of pH and temperature on the morphology and phases of co-precipitated hydroxyapatite

This paper reports a high-yield process to fabricate biomimetic hydroxyapatite nano-particles or nano-plates. Hydroxyapatite is obtained by simultaneous dripping of calcium chloride and ammonium hydrogen phosphate solutions into a reaction vessel. Reactions were carried out under various pH and temperature conditions. The morphology and phase composition of the precipitates were investigated using scanning electron microscope and X-ray diffraction. The analyses showed that large plates of calcium hydrophosphate are formed at neutral or acidic pH condition. Nanoparticles of hydroxyapatite were obtained in precipitates prepared at pH 9–11. Hydroxyapatite plates akin to seashell nacre were obtained at 40 °C and pH 9. This material holds promise to improve the strength of hydroxyapatite containing composites for bone implant or bone cement used in orthopaedic surgeries. The thermodynamics of the crystal growth under these conditions was discussed. An assembly mechanism of the hydroxyapatite plates was proposed according to the nanostructure observations.