Cell adhesion and accelerated detachment on the surface of temperature-sensitive chitosan and poly(N-isopropylacrylamide) hydrogels

A series of temperature-sensitive poly(NIPAAm-co-CSA) hydrogels were synthesized by the copolymerization of acrylic acid-derivatized Chitosan (CSA) and N-isopropylacrylamide (NIPAAm) in aqueous solution. Their swelling properties and L929 cell adhesion and detachment behaviors were studied. It was found that poly(NIPAAm-co-CSA) hydrogels were temperature-sensitive associated with the roles of the component PNIPAAm. Most significantly, poly(NIPAAm-co-CSA) hydrogels exhibited simultaneously good swelling properties. The investigation of L929 cell adhesion and detachment of poly(NIPAAm-co-CSA) hydrogels indicated the cell adhesion and spreading was higher on the surface of poly(NIPAAm-co-CSA) hydrogels than that of PNIPAAm hydrogel at 37 degrees C due to the incorporation of CS, which having excellent cell affinity. Poly(NIPAAm-co-CSA) hydrogels showed more rapid detachment of cell sheet compared to PNIPAAm hydrogel because of the highly hydrophilic and hygroscopic nature of CS chains when reducing the culture temperature from 37 degrees C to 20 degrees C.     

温度/pH敏感性Semi-IPN水凝胶的制备与性能

以N-乙烯基乙酰胺（NVA）、醋酸乙烯酯（VAc）和甲基丙烯酸-N,N′-二甲氨基乙酯（DMAEMA）为原料,通过自由基聚合制备了PDMAEMA/P（NVA-co-VAc）半互穿网络（Sem-iIPN）水凝胶。实验结果表明,该水凝胶具有较好的温度敏感性、pH敏感性、溶胀-退胀可逆性。随着温度的逐渐升高,凝胶的溶胀率随之...     

壳聚糖/聚(N-异丙基丙烯酰胺)全互穿网络水凝胶的制备及性能

以壳聚糖(CS)和N-异丙基丙烯酰胺(NIPAAm)为原料,N,N'-亚甲基双丙烯酰胺(BIS)为交联剂,制备具有温度和pH值双敏感性的全互穿网络水凝胶(Full-IPN);利用红外光谱(FT-IR)对其分子结构进行表征,扫描电镜(SEM)观察其内部形貌,并通过DSC对其低临界溶解温度(LCST)进行表征,最后研究了不...     

PNIPAAm/CMC半互穿网络水凝胶的合成及性质

以N-马来酰化壳聚糖为交联剂,N-异丙基丙烯酰胺(NIPAAm)为单体,羧甲基纤维素钠(CMC)为半互穿材料,在水溶液中通过自由基聚合制备了PNIPAAm/CMC半互穿网络水凝胶.所合成的水凝胶的低临界溶解温度(LCST)在33℃左右,CMC的加入对水凝胶的LCST无显著影响,但随着CMC用量的增加,水凝胶的温度敏感性...     

Novel PAAm/Laponite clay nanocomposite hydrogels with improved cationic dye adsorption behavior

A nanocomposite (NC) hydrogel was prepared by incorporating the nanoclay (Laponite (Lap) XLS) into a poly(acrylamide) (PAAm) hydrogel by the in situ polymerization method without any organic cross-linker. The parameters pertaining to the swelling (Q) and diffusion (D) of water for the PAAm/Lap NC hydrogels were estimated. The crystal violet (CV) dye adsorption properties of the PAAm/Lap NC hydrogels were investigated. The adsorption of CV dye by the hydrogel increases as the concentration of the dye increases. The cationic dye adsorption ability of the NC hydrogel increased with increasing clay content in the NC hydrogel. The NC hydrogels containing CV dye were characterized by FT-IR. A sigmoidal type of adsorption isotherm was observed for the CV-NC hydrogels. The effects of heat treatment on the dye adsorption behavior of the NC hydrogels were studied.     

Preparation,properties, and drug release of thermo- and pH-sensitive poly((2-dimethylamino)ethyl methacrylate)/poly(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethylacrylamide) semi-IPN hydrogels

In this paper, a series of semi-interpenetrating polymer network (semi-IPN) hydrogels based on poly((2-dimethylamino)ethyl methacrylate)/poly (N,N-diethylacrylamide) (PDMAEMA/PDEA) were synthesized by changing the initial PDMAEMA/DEA molar ratio at room temperature. The influence of this additive on the property of resulting PDEA hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that the semi-IPN hydrogels have interconnected porous network structures. The glass transition temperature (T _g) of the semi-IPN hydrogels was observed by differential scanning calorimetry (DSC). Equilibrium swelling ratio (ESR), swelling and deswelling dynamics of the hydrogels responding to temperature and pH were investigated in detail. Compared to PDEA, the semi-IPN hydrogels exhibited excellent mutative values in response to an alternation of the temperature and pH, and showed fast swelling and deswelling rates in response to temperature and pH change. The release behaviors of the model drug, aminophylline, were found dependent on hydrogel compositions and environmental temperature. These results suggest that the stimuli semi-IPN hydrogel have potential application as intelligent drug carriers.     

Synthesis and characterization of partially biodegradable and thermosensitive hydrogel

A partially biodegradable and thermosensitive hybrid hydrogel network (DAN series) based on dextran-allylisocyanate (Dex-AI) and poly(N-isopropylacrylamide) (PNIPAAm) was synthesized via UV photocrosslinking. These hybrid hydrogels were characterized in terms of their chemical structure, thermal, mechanical, morphological and temperature-induced swelling properties. The effect of the composition ratio of Dex-AI to PNIPAAm on such properties were examined. The differential scanning calorimetry data show that this Dex-AI/PNIPAAm hybrid network has an increased lower critical solution temperature (LCST) and glass transition temperature (Tg) with an increase in the Dex-AI content. The interior morphology of these hybrid hydrogels revealed a decreased porous microstructure with an increase in the Dex-AI content in the hybrid network. Furthermore, if the Dex-AI composition became too high, a distinctive network structure with two different microporous structures appeared. The mechanical properties of these hybrid hydrogels also increased with an increase in the Dex-AI content. The temperature dependence of the swelling ratio, the deswelling kinetics as well as the reswelling kinetics was also characterized by gravimetric method. When comparing with a normal PNIPAAm hydrogel, these Dex-AI/PNIPAAm hybrid networks, due to the presence of Dex-AI moiety, also show improved temperature-induced intelligent properties, such as the faster and controllable response dynamics, which may find promising applications in a wide variety of fields, such as biomedical and bioengineering fields.     

Recent Advances in Poly(N-isopropylacrylamide) Hydrogels and Derivatives as Promising Materials for Biomedical and Engineering Emerging Applications

Temperature-sensitive (thermosensitive) hydrogels, which are part of the family of stimulus-sensitive hydrogels, consist of water-filled polymer networks that display a temperature-dependent degree of swelling. Thermosensitive hydrogels, which can undergo phase transition or swell/de-swell as temperature changes, have great potential in various technological and biomedical purposes for a number of reasons: their temperature response is reversible, hydrogels are stable and easy to prepare, they can be biocompatible and also be suitably combined with other organic and inorganic materials, resulting in new materials with outstanding properties. Among thermosensitive hydrogels poly(N-isopropylacrylamide) (PNIPAAm) is the most extensively studied because it brings together the best properties of these materials. Consequently, in the past few years, a wide number of applications and new chemical processes to prepare PNIPAAm and their derivatives are being proposed. The objective of this review is to summarize the fundamentals of thermosensitive hydrogels and recent advances in preparation and both technological and biomedical applications of thermosensitive hydrogel, with a special focus on PNIPAAm and their derivatives. Special attention has been given to the discussion of challenges and future research perspectives based on new horizons not yet considered.     

Release of BSA from porous matrices constituted of alginate–Ca and PNIPAAm-interpenetrated networks

The synthesis of thermosensitive Interpenetrating Polymer Network (IPN) hydrogels and the release of Bovine Serum Albumin (BSA) from the hydrogels were reported. The hydrogels, constituted of poly(N-isopropyl acrylamide) PNIPAAm network interpenetrated in alginate–Ca²⁺ network, were synthesized in a two-stepped process. In the first step, PNIPAAm network was synthesized from an aqueous solution containing N-isopropyl acrylamide (NIPAAm) monomers and N,N′-methylene-bis-acrylamide (MBAAm) co-monomers, and sodium alginate (SA) (1 or 2% w/v). The concentration of NIPAAm monomers in the hydrogel-forming solution was always 2.5, 5.0 or 10.0% (w/v). In the second step, alginate–Ca²⁺ networks were formed by immersion of the membrane, obtained on the first step, in a 1.0% (w/v) aqueous calcium chloride. The IPN hydrogels were characterized as a function of temperature (from 25 to 45 °C) through the following measurements: drop water contact angle (DWCA), compression elastic modulus (E) and cross-linking density (ν_e). The morphology was investigated using scanning electronic microscopy (SEM). In vitro release of BSA from the hydrogels was monitored by UV–Vis spectroscopy at 22 °C and 37 °C. DWCA results showed a decrease in the hydrogel hydrophilicity when the temperature and/or the PNIPAAm amount on hydrogels were increased. PNIPAAm-loader hydrogels are more compacted and presented elevated rigidity, mainly above 35 °C. This trend was attributed to the collapsing of PNIPAAm chains as the hydrogels were warmed above its Lower Critical Solution Temperature (LCST), which in aqueous solution is ca. 32–33 °C. The amount of BSA released from the alginate–Ca²⁺/PNIPAAm hydrogels changes inversely to both amount of PNIPAAm and temperature. The transport of BSA from the hydrogels was evaluated through a conventional model. In the lesser-compacted hydrogels the release occurs mostly by diffusion. In the more compacted ones the chain relaxation contributes to the BSA release. Thus, the alginate–Ca²⁺/PNIPAAm IPN-typed matrixes may be considered as smart hydrogels for the release of BSA, because the amount and rate of BSA released may be tailored by both the NIPAAm concentration in the hydrogel-forming solution and the control of temperature of hydrogel.     

Synthesis and characterization of matrix metalloprotease sensitive-low molecular weight hyaluronic acid based hydrogels

Hyaluronic acid is a naturally derived glycosaminoglycan (GAG) involved in biological processes. A low molecular weight hyaluronic acid (50 kDa)-based hydrogel was synthesized using acrylated hyaluronic acid. Matrix metalloproteinase (MMP) sensitive hyaluronic acid-based hydrogels were prepared by conjugation with two different peptides: cell adhesion peptides containing integrin binding domains (Arg-Gly-Asp: RGD) and a cross-linker with MMP degradable peptides to mimic the remodeling characteristics of natural extracellular matrices (ECMs) by cell-derived MMPs. Mechanical properties of these hydrogels were evaluated with different molecular weights of acrylated hyaluronic acid (10 kDa and 50 kDa) cross-linked by MMP sensitive peptides by measuring elastic modulus, viscous modulus, swelling ratio and degradation rate. The MMP sensitive hydrogel based on the 50 kDa hyaluronic acid showed a 31.5-fold shorter gelation time, 4.7-fold higher storage modulus and 0.51-fold smaller swelling ratio than those of the hydrogel based on the 10 kDa. Degradation rate was dependent on MMP sensitivity of the peptide cross-linker. MMP sensitive hyaluronic acid based hydrogels were degraded faster than MMP insensitive-hyaluronic acid-based hydrogels. Human mesenchymal stem cells (MSCs) were cultured in MMP-sensitive or insensitive hyaluronic acid-based hydrogels (50 kDa hyaluronic acid) and/or immobilized cell adhesive RGD peptides. Cells cultured in the MMP-sensitive hydrogel with RGD peptides showed dramatic cell spreading compared with that of the control, which remained round. This MMP-sensitive low molecular weight hyaluronic acid-based hydrogel could be useful in tissue engineering by improving tissue defect regeneration and tissue remodeling.     

Chemistry between crosslinks affects the properties of peptide hydrogels

Protein hydrogels were prepared by substituting ovalbumin with different concentrations of ethyl vinyl sulfone (EVS) or acrylic acid (AA) and crosslinking with divinyl sulfone (DVS). Fourier transform-infrared (FT-IR) spectroscopic studies confirmed the addition of EVS, AA, and DVS onto the protein. Swelling was assessed as a function of pH in the range of 2.5 to 9.4 and ionic strength. The elastic modulus of the gels was determined in shear and compression. Stress relaxation was assessed in compression. The substituent highly affected swelling and modulus with both hydrogels displaying non-Gaussian behavior in the range of hydrogel environments studied. Acrylic acid substituted ovalbumin exhibited a decreasing modulus with increasing swelling behaving as a polyelectrolyte with low added salt content. Ethyl vinyl sulfone substituted ovalbumin displayed an increasing modulus with swelling originating in the finite extensibility of the highly swollen chains. AA-substituted ovalbumin showed higher modulus and reduced swelling compared to EVS-substituted ovalbumin because of its ability to hydrogen and ionic bond to other molecules.     

Influence of polyelectrolyte on the thermosensitive property of PNIPAAm-based copolymer hydrogels

A new family of poly(NIPAAm-co-2-acrylamido-2-methyl-1-propanesulfonic acid) [P(NIPAAm-co-AMPSA)] hydrogels was synthesized by incorporating negative charged AMPSA to the backbone of the PNIPAAm-based hydrogel. The effect of polyelectrolyte (i.e., PAMPSA) on the thermosensitive property of PNIPAAm hydrogels was investigated. It was found that P(NIPAAm-co-AMPSA) hydrogels exhibited unique honey-comb-like 3D porous structure having rigid cell wall as well as enhanced mechanical property. The incorporation of AMPSA into PNIPAAm backbones also led to a significant increase in swelling capability at room temperature when comparing to pure PNIPAAm hydrogels. In addition, the shrinking rate upon heating was significantly improved if the AMPSA content in P(NIPAAm-co-AMPSA) hydrogels was less than 10 wt%.     

Thermoresponsive hydrogel with rapid response dynamics

Intelligent hydrogels, particularly poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogels, have attracted extensive interest because the soft wet hydrogels can change their shapes in response to the small changes of environmental factors like temperature. In order to fully make use of this unique property of PNIPAAm-based hydrogels, the response rates of the PNIPAAm hydrogels have to be improved since the dynamics property is critical to certain applications of this material. In this paper, the thermo-sensitive PNIPAAm hydrogels were successfully synthesized by carrying out the polymerization of N-isopropylacrylamide monomer in vacuum (–100 kPa) at room temperature (22 °C). The resultant hydrogel has tremendously improved shrinking rate as well as the large volume changes upon temperature stimulation when comparing with the normal PNIPAAm hydrogel. The SEM micrographs revealed that the improved properties were attributed to the macroporous network structure generated during the synthesis under vacuum.     

Swelling and mechanical behaviors of carbon nanotube/poly(vinyl alcohol) hybrid hydrogels

In this paper, carbon nanotubes (CNTs) were added into poly(vinyl alcohol) (PVA) hydrogels to modify their mechanical properties. A series of CNT/PVA hybrid hydrogels were prepared by freezing/thawing method. The mechanical and swelling properties of all hybrid hydrogels are better than those of the original PVA hydrogel. Especially, for CNTP-0.5 specimen with 0.5% w/w CNTs, its tensile modulus, tensile strength and strain at break are increased by 78.2%, 94.3% and 12.7%, respectively. And its swelling behavior is different from that of the pure PVA hydrogel. Its final swelling ratios at room temperature and 310 K are increased by 35.7% and 44.9%, respectively.     

PVA-PAAIPN水凝胶的制备及其溶胀性质研究

利用化学交联和循环冰冻-解冻相结合的顺序逼近法，制备了由和聚乙烯醇（PVA）和聚丙烯酸（PAA）复合的具有互穿聚合物网络（IPN）结构的高分子水凝胶。研究了交联剂含量，PAA含量和温度对水凝胶溶胀性质的影响，实验结果表明，30℃时，交联剂含量为1.0mol%的凝胶溶胀度最大，凝胶中PAA含量越大，凝胶的溶胀度越大；具有IPN结构的凝胶具有温度敏感性质；调节凝胶中PAA和交联剂的含量，可以控制凝胶突变体系的大小。     

Thermo- and pH-sensitive IPN hydrogels based on PNIPAAm and PVA-Ma networks with LCST tailored close to human body temperature

Interpenetrating polymer network (IPN) hydrogels based on chemically modified poly(vinyl alcohol) (or PVA-Ma), with different degrees of substitution (DS), and poly(N-isopropylacrylamide) (or PNIPAAm) were obtained and characterized in this work. The PVA-Ma/PNIPAAm membrane hydrogels were prepared in two steps. In the first step the PVA-Ma hydrogels (with using PVA-Ma with different DS) were prepared by the reaction of double bonds on PVA-Ma, using the persulfate/TEMED pathway. In the second step the PNIPAAm network was prepared within the parent PVA-Ma network at different PVA-Ma/NIPAAm ratios using a photoreaction pathway. The studies show that degree of swelling of PVA-Ma/PNIPAAm IPN hydrogels is dependent on both temperature and pH of the soaking solution. The LCST of PVA-Ma/PNIPAAm IPN hydrogels, which was determined by measuring the intensity of light transmitted through the swollen hydrogels, can be tailored closer to human body temperature. Furthermore, SEM images showed that the IPN hydrogels present characteristic morphology as compared to parent PVA-Ma networks. IPN hydrogels presented lower cytotoxicity as compared to respective PVA-Ma hydrogels but the increase in the PVA-Ma/NIPAAm ratio allows the respective hydrogels being lesser cytocompatibles. The IPN hydrogels synthesized in this work presented characteristics that potentize their application as biomaterials, drug carriers, artificial muscles and treatment of wound.     

半纤维素的提取及其温敏性水凝胶的制备

以采用稀碱抽提法从植物残料中提取的半纤维素为原料,通过化学交联法,自由基聚合将单体接枝到半纤维素链上,并交联温敏性单体,促使形成共聚交联网络结构,得到温度敏感性水凝胶。通过物理交联法,半纤维素与壳聚糖物理交联,制备半纤维素基水凝胶。采用交联度测定、溶胀动力学研究、红外光谱、差示量热等手段对化学交联和物理交联两种方法制得的半纤维素基水凝胶温度响应性能进行表征。结果表明:10%NaOH提取的半纤维素得率最高;化学交联法和物理交联法制得的半纤维素基水凝胶,都具有温度负响应特性,为温敏性水凝胶。作为当下较为热门材料,广泛应用于医疗、农业和生物组织工程材料等领域。     

聚丙烯酸类水凝胶的制备及其在碱性溶液中的pH敏感性

以（NH₄）₂S₂O₈和NaHSO₃为氧化-还原引发剂、N,N′-亚甲基双丙烯酰胺（MBA）为交联剂,采用自由基水溶液聚合方法,分别合成了聚丙烯酸（PAAc）、聚丙烯酰胺（PAAm）和系列丙烯酸（AAc）质量分数（fAAc）不同的聚（丙烯酸-co-丙烯酰胺）（P（AAc-co-AAm））水凝胶。进而分别对其在碱性缓冲溶液和NaOH溶液中的pH敏感行为进行了探讨。结果表明,PAAc和P（AAc-co-AAm）凝胶在2种溶液中均具有优良的pH响应行为,且在NaOH溶液中的溶胀比大于缓冲溶液中;而PAAm凝胶仅在NaOH溶液中具有pH敏感性。2种溶液中,随f（AAc）的增加,P（AAc-co-AAm）凝胶的平衡溶胀比（ESR）增大;但在缓冲溶液中,当f（AAc）≥20%时,P（AAc-co-AAm）凝胶的溶胀行为与PAAc相似,而当f（AAc）<20%时,其溶胀则同时表现出PAAc和PAAm凝胶的溶胀特性。溶胀机理分析表明,凝胶的溶胀主要受聚合物网络内静电排斥作用和离子屏蔽效应控制。     

Hepta(3,3,3-trifluoropropyl) polyhedral oligomeric silsesquioxane-capped poly(N-isopropylacrylamide) telechelics: synthesis and behavior of physical hydrogels

Hepta(3,3,3-trifluoropropyl) polyhedral oligomeric silsesquioxane (POSS)-capped poly(N-isopropylacrylamide) (PNIPAAm) telechelics with variable lengths of PNIPAAm midblocks were synthesized by the combination of reversible addition-fragmentation chain transfer polymerization (RAFT) and the copper-catalyzed Huisgen 1,3-cycloaddition (i.e., click chemistry). The POSS-capped trithiocarbonate was synthesized and used as the chain transfer agent for the RAFT polymerization of N-isopropylacrylamide. The organic-inorganic amphiphilic telechelics were characterized by means of nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography (GPC). Atomic force microscopy (AFM) shows that all the POSS-capped PNIPAAm telechelics exhibited microphase-separated morphologies, in which the POSS terminal groups were self-assembled into the microdomains and dispersed into the continuous PNIPAAm matrices. The POSS nanodomains could behave as the physical cross-linking sites and as a result the physical hydrogels were formed while these POSS-capped PNIPAAm telechelics were subjected to the solubility tests with water. These physical hydrogels possessed well-defined volume phase transition phenomena and displayed rapid reswelling and deswelling thermoresponsive behavior compared to control PNIPAAm hydrogel.     

Dynamic mechanical characterization of hydrogel blends of poly(vinyl alcohol-vinyl acetate) with poly(acrylic acid) or poly(vinyl pyrrolidone)

Transparent hydrogels were prepared by blending solutions of poly(vinyl alcohol-vinyl acetate) with either poly(acrylic acid) or poly(vinyl pyrrolidone) in the presence of glutaraldehyde as a crosslinking agent. The network obtained from the poly(vinyl pyrrolidone) system was subjected to various thermal treatments, the effects of which have been studied. Dynamic mechanical analysis was used to characterize the hydrogels and to establish the suitability of these blends for use in biomedical applications. The swelling behaviour was followed under dynamic loads as well as by mass difference. Different frequencies were used to study the dynamic properties of the hydrogel blends which showed an increase in storage modulus with increasing frequency. A comparison of modulus values obtained dynamically were in agreement with data obtained mechanically in tension.This paper was accepted for publication after the 1995 Conference of the European Society of Biomaterials. Oporto, Portugal, 10–13 September.