Characterization of Mass and Swelling of Hydrogel Microstructures using MEMS Resonant Mass Sensor Arrays

The use of hydrogels for biomedical engineering, and for the development of biologically inspired cellular systems at the microscale, is advancing at a rapid pace. Microelectromechanical system (MEMS) resonant mass sensors enable the mass measurement of a range of materials. The integration of hydrogels onto MEMS resonant mass sensors is demonstrated, and these sensors are used to characterize the hydrogel mass and swelling characteristics. The mass values obtained from resonant frequency measurements of poly(ethylene glycol)diacrylate (PEGDA) microstructures match well with the values independently verified through volume measurements. The sensors are also used to measure the influence of fluids of similar and greater density on the mass measurements of microstructures. The data show a size-dependent increase in gel mass when fluid density is increased. Lastly, volume comparisons of bulk hydrogels with a range polymer concentration (5% to 100% (v/v)) show a non-linear swelling trend.     

自由基聚合法制备聚乙二醇双丙烯酸酯水凝胶

以过二硫酸胺(APS)/四甲基乙二胺(TMEDA)氧化-还原体系为引发体系,通过活性自由基溶液聚合法制备了交联网状聚乙二醇双丙烯酸酯(PEGDA)共聚物水凝胶支架,探讨了APS/TMEDA的引发聚合机理。研究结果表明,单体分子量越大,凝胶化时间越短,凝胶化时间随着PEGDA单体浓度的增大、温度的升高和加速剂用量的增大而减小。研究了不同单体浓度对水凝胶溶胀度及力学性能的影响,结果表明,单体溶液浓度越大,水凝胶的平衡溶胀率越小、压缩模量越强。     

Preparation and properties of collagen/modified hyaluronic acid hydrogel for biomedical application

Hydrogels composed of collagen and hyaluronic acid are types of crosslinked water-swellable polymers and possess vast potential for applications in the medical industry. Collagen (Co) is the major structural protein of connective tissues such as skin, tendon and cartilage. Hyaluronic acid (HA) is a non-immunogenic, non-adhesive glycosaminoglycan that has a high water absorption property and plays significant roles in several cellular processes. The purpose of this study is to prepare a collagen (Co)-modified hyaluronic acid (MHA) hydrogel and investigate its potential utility for biomedical products such as wound dressing materials. Collagen (Co, type I) was obtained from pig skin and mucopolysaccharide-HA was modified by a poly (ethylene glycol) diglycidyl ether (PEGDGE) crosslinker. Thermal stability, swelling behavior, and mechanical strength of Co-MHA hydrogel according to different mass ratios of Co and MHA in hydrogel networks were investigated. The physical properties of the hydrogel were measured by SEM, Differential Scanning Calorimetry (DSC), Thermal Gravity Analysis (TGA), and a Universal Testing Machine (UTM). The cell viability of Co-MHA hydrogel was also evaluated using an in vitro MTT assay.     

Synthesis, swelling and drug release behavior of poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) hydrogel

In this study, poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) (poly(DEA-co-NHMAA)) hydrogels were synthesized by changing the initial DEA/NHMAA mole ratio, N,N'-methylenebisacrylamide and total monomer concentration. The thermosensitive and mechanical performances were optimized by altering the above parameters. The hydrogels were characterized by using Fourier transform infrared (FTIR) spectroscope and scanning electron microscope (SEM). In comparison with the PDEA hydrogel, the equilibrium swelling ratio (ESR) and lower critical solution temperature (LCST) of the hydrogels increased with the increase of NHMAA content in the feed. The swelling kinetics was also studied. The release behaviors of the model drug, aminophylline, are found dependent on hydrogel composition and environmental temperature, which suggests that these materials have potential application as intelligent drug carriers.     

Multicomponent DNA Polymerization Motor Gels

Hydrogels with the ability to change shape in response to biochemical stimuli are important for biosensing, smart medicine, drug delivery, and soft robotics. Here, a family of multicomponent DNA polymerization motor gels with different polymer backbones is created, including acrylamide‐co‐bis‐acrylamide (Am‐BIS), poly(ethylene glycol) diacrylate (PEGDA), and gelatin‐methacryloyl (GelMA) that swell extensively in response to specific DNA sequences. A common mechanism, a polymerization motor that induces swelling is driven by a cascade of DNA hairpin insertions into hydrogel crosslinks. These multicomponent hydrogels can be photopatterned into distinct shapes, have a broad range of mechanical properties, including tunable shear moduli between 297 and 3888 Pa and enhanced biocompatibility. Human cells adhere to the GelMA‐DNA gels and remain viable during ≈70% volumetric swelling of the gel scaffold induced by DNA sequences. The results demonstrate the generality of sequential DNA hairpin insertion as a mechanism for inducing shape change in multicomponent hydrogels, suggesting widespread applicability of polymerization motor gels in biomaterials science and engineering.     

聚丙烯酸/活性炭复合凝胶的制备及溶胀行为

采用自由基溶液聚合的方法,以过硫酸铵(APS)为引发剂,N,N′-亚甲基双丙烯酰胺(NNMBA)为交联剂,制备了聚丙烯酸(PAA)复合活性炭凝胶(PAA/AC)。考察了凝胶在生理盐水和不同pH值缓冲溶液中的平衡溶胀比及溶胀动力学,结果表明,活性炭能有效提高PAA凝胶的平衡溶胀比。蒸馏水中PAA/AC凝胶的平衡溶胀比可达到303(g/g),约为PAA凝胶平衡溶胀比的2.3倍;生理盐水(0.9%g/mL NaCl水溶液)中PAA/AC凝胶的平衡溶胀比可达到60(g/g),约为PAA凝胶平衡溶胀比的2.4倍;在实验设计的pH范围内PAA/AC凝胶的平衡溶胀比比PAA凝胶更高,具有更好的pH值敏感特性。     

等离子改性条件对PEGDA/HEMA凝胶亲水性及表面能的影响

采用氩等离子对聚乙二醇双丙烯酸酯(PEGDA)/甲基丙烯酸-2-羟基乙酯(HEMA)共聚物凝胶进行表面改性,对膜材料进行了光电子能谱(XPS)分析,并讨论了等离子处理时间及功率对凝胶亲水性及表面能的影响。研究结果表明,经等离子处理后凝胶表面引入了含氧极性基团,氧的含量从未处理的23%增加到26%,使材料亲水性得到改善;由于引入极性基团,材料的表面能随等离子处理时间和功率的增加而增加,从未处理前的45.9 mJ/m2增加到72.5 mJ/m2,极性力分量γPs随等离子体处理功率和时间的变化规律与表面能γs基本一致。     

Controlled release of drugs from gradient hydrogels for high-throughput analysis of cell-drug interactions

In this paper, we report a method to fabricate microengineered hydrogels that contain a concentration gradient of a drug for high-throughput analysis of cell-drug interactions. A microfluidic gradient generator was used to create a concentration gradient of okadaic acid (OA) as a model drug within poly(ethylene glycol) diacrylate hydrogels. These hydrogels were then incubated with MC3T3-E1 cell seeded glass slides to investigate the cell viability through the spatially controlled release of OA. The drug was released from the hydrogel in a gradient manner and induced a gradient of the cell viability. The drug concentration gradient containing hydrogels developed in this study have the potential to be used for drug discovery and diagnostics applications due to their ability to simultaneously test the effects of different concentrations of various chemicals.     

Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair

The fabrication of osteochondral tissue engineering scaffolds comprised of different layers is a big challenge. Herein, bilayers comprised of double network hydrogels with or without nano hydroxyapatite (HAp) were developed by exploiting the radical reaction of poly(ethylene glycol) diacrylate (PEGDA) and the Schiff-base reaction of N-carboxyethyl chitosan (CEC) and oxidized hyaluronic acid sodium (OHA) for osteochondral tissue engineering. The bilayered osteochondral scaffold was successfully fabricated based on the superior self-healing property of both hydrogels and evaluated by scanning electron microscopy, macroscopic observation and mechanical measurements. In addition, the hydrogels exhibited good biocompatibility as demonstrated by the in vitro cytotoxicity and in vivo implantation tests. The results indicated that the bilayered hydrogel had great potential for application in osteochondral tissue engineering.     

Tuning PEG-DA hydrogel properties via solvent-induced phase separation (SIPS)()

Poly(ethylene glycol) diacrylate (PEG-DA) hydrogels are widely utilized to probe cell-material interactions and ultimately for a material-guided approach to tissue regeneration. In this study, PEG-DA hydrogels were fabricated via solvent-induced phase separation (SIPS) to obtain hydrogels with a broader range of tunable physical properties including morphology (e.g. porosity), swelling and modulus (G'). In contrast to conventional PEG-DA hydrogels prepared from an aqueous precursor solution, the reported SIPS protocol utilized a dichloromethane (DCM) precursor solution which was sequentially photopolymerized, dried and hydrated. Physical properties were further tailored by varying the PEG-DA wt% concentration (5 wt%-25 wt%) and M(n) (3.4k and 6k g mol (-1)). SIPS produced PEG-DA hydrogels with a macroporous morphology as well as increased G' values versus the corresponding conventional PEG-DA hydrogels. Notably, since the total swelling was not significantly changed versus the corresponding conventional PEG-DA hydrogels, pairs or series of hydrogels represent scaffolds in which morphology and hydration or G' and hydration are uncoupled. In addition, PEG-DA hydrogels prepared via SIPS exhibited enhanced degradation rates.     

聚乙二醇双丙烯酸酯的紫外光聚合

以1-[4-(2-羟乙氧基)-苯基]-2-羟基-2甲基丙酮为光引发剂,通过紫外光自由基聚合制备了交联网状聚乙二醇双丙烯酸酯共聚物水凝胶。研究结果表明,随着光照时间的增加,单体共聚的转化率提高;随着引发剂浓度的增大,单体溶液中自由基增多,聚合速度增大。FI-IR结果表明PEGDA单体经30min紫外光照射后聚合完全。     

Synthesis and properties of poly(ethylene glycol) macromer/β-chitosan hydrogels

Semi-interpenetrating polymer network (semi-IPN) hydrogels composed of -chitosan and poly(ethylene glycol) diacrylate macromer (PEGM) were synthesized and characterized for the application as potential biomedical materials. The mixture of PEGM and -chitosan, dissolved in water including a small amount of acetic acid, was cast to prepare hydrogel films, followed by a subsequent crosslinking with 2,2-dimethoxy-2-phenylacetophenone as a non-toxic photoinitiator by ultraviolet irradiation. Photocrosslinked hydrogels exhibited relatively high equilibrium water content in the range 77–83% which is mainly attributed to the free water content rather than to the bound water, hydrogen bonded with components in semi-IPN hydrogels. The crystallinity, thermal properties and mechanical properties of semi-IPN hydrogels were studied. All the photocrosslinked hydrogels revealed a remarkable decrease in crystallinity. The glass transition temperatures, Tg, of crosslinked PEGM segment in semi-IPNs increased compared with poly(ethylene glycol) itself. However, with increasing -chitosan content their Tg decreased owing to the higher degree of crosslinking. The tensile strengths of semi-IPNs in dry state were rather high, but those of hydrogels in wet state decreased drastically.     

Swelling behavior and drug release of NIPAAm/PEGMEA copolymeric hydrogels with different crosslinkers

Poly(ethylene glycol) methylether acrylate (PEGMEA) and tetraethylene glycol diacrylate (TEGDA) were first synthesized. The thermosensitive hydrogels were then prepared from N-isopropylacrylamide (NIPAAm), PEGMEA, and three crosslinkers with different structures such as N, N′-methylene-bis-acrylamide (NMBA), TEGDA, and poly(ethylene glycol) dimethacrylate (EGDMA). The influence of polymerization factors such as the kind and amount of crosslinker and initial total monomer concentration on the swelling behavior, gel strength, effective crosslinking densities, and number-average molecular weight between crosslink points ( ) for the present copolymeric hydrogels was investigated. The results indicate that the swelling ratios for the present copolymeric gels decrease with increase in temperature. In addition, the results also showed that the higher swelling ratios for the present gels prepared from TEGDA were obtained due to the larger space between the gel networks. The crosslinking density depends on the swelling ratio and the kind and extent of crosslinker. In addition, the drug release behavior for the present copolymeric gels was investigated.     

白炭黑原位复合聚丙烯酰胺水凝胶的合成及次级网络对流变行为的影响

采用水溶液聚合法,通过丙烯酰胺与白炭黑原位复合,制备出复合聚丙烯酰胺凝胶.采用高级流变仪和红外吸收光谱证实了白炭黑与聚丙烯酰胺形成的次级网络的存在,通过对比不同白炭黑填充量和不同吸水倍数对聚丙烯酰胺水凝胶模量、损耗角正切、零切黏度和流动指数的影响,发现白炭黑的加入对聚丙烯酰胺凝胶力学性能的贡献,随着白炭黑用量在0%～3...     

新型胶原/聚丙烯酸互穿网络pH敏感水凝胶的制备及性能研究

以Bis为交联剂,采用互穿网络(IPN)技术制备胶原/聚丙烯酸pH敏感水凝胶.研究了不同配比的水凝胶的溶胀动力学、pH敏感性及pH溶胀-退胀特性,并利用傅里叶变换红外光谱法(FTIR)和差示量热扫描法(DSC)对其结构进行表征.结果显示:制备的水凝胶具有较快的溶胀速率,在13min时吸水率可达93%左右;水凝胶有明显的pH敏感性且pH溶胀-退胀可逆性良好.FTIR和DSC结果表明,在保持胶原三股螺旋结构的同时,材料间形成了互穿网络,材料的热稳定性显著提高,从而扩大了材料的应用范围.     

温度和pH双重敏感型聚氨酯水凝胶的制备及性能

以聚乙二醇(PEG)、4,4’-二苯基甲烷二异氰酸酯(MDI)、三羟甲基丙烷(TMP)为主要原料,分别采用1,4-丁二醇(BDO)、N-甲基二乙醇胺(MDEA)、2,2-二羟甲基丙酸(DMPA)为扩链剂,制备了3种聚氨酯水凝胶Hydrogel(a)、Hydrogel(b)、Hydrogel(c)。通过红外光谱、差示扫描量热分析、X射线衍射和溶胀实验对水凝胶的结构和性能进行了分析。研究结果表明,温度敏感链段(PEG)和pH敏感基团(-N(CH_3)-、-COOH)均成功地引入到了水凝胶分子链中;3种水凝胶的相转变温度分别为55℃、60℃和64℃,且合成后水凝胶中PEG的结晶结构仍然存在;当水溶液温度从45℃上升到60℃时,3种水凝胶的平衡溶胀度均显著减小,显示出温度敏感性;当pH从4.0上升到7.0时,Hydrogel(c)的平衡溶胀度从11.5增大到15.5,当pH从8.5上升到11.5时,Hydrogel(b)的平衡溶胀度从12.9减小到10.0,均显示出pH敏感性;在不同温度(25℃和65℃)和pH(2.5和11.5)的水溶液中反复溶胀,水凝胶Hydrogel(b)和Hydrogel(c)均表现出良好的可逆性和稳定性。     

Corneal epithelialisation on surface-modified hydrogel implants: artificial cornea

The objective was to investigate corneal re-epithelialisation of surface-modified polymethacrylate hydrogel implants in order to evaluate them as potential materials for an artificial cornea. Polymethacrylate hydrogels were modified with amines and then coated with different extracellular matrix proteins (collagen I, IV, laminin and fibronectin). The modified hydrogels were surgically implanted into bovine corneas maintained in a 3-D culture system for 5 days. The epithelial growth across the implant surface was evaluated using fluorescent, light and electron microscopy. Full epithelialisation was achieved on 1,4-diaminobutane-modified hydrogels after coating with collagen IV. Hydrogels modified with 1,4-diaminobutane but without further coating only showed partial re-epithelialisation. Hydrogels modified with other amines (1,2-diaminoethane or 1,3-diaminopropane) showed only partial re-epithelialisation; further coating with extracellular matrix proteins improved epithelialisation of these surfaces but did not result in complete re-epithelialisation. Evaluation of the corneas implanted with the 1,4-diaminobutane-modified hydrogels coated with collagen IV showed that the artificial corneas remain clear, integrate well and become covered by a healthy stratified epithelium. In conclusion the 1,4-diaminobutane surface-modified hydrogel coated with collagen IV supported the growth of a stable stratified epithelium. With further refinement this hydrogel has the potential to be used clinically for an artificial cornea.     

聚乙二醇改性纳米纤维素/聚乙烯醇复合水凝胶的制备及性能

通过酸碱处理和机械研磨结合的方法制备纳米纤维素(CNFs),并利用冻融循环法分别制备了聚乙烯醇(PVA)和纳米纤维素/聚乙烯醇(CNFs/PVA)复合水凝胶,以及聚乙二醇(PEG)改性PVA和CNFs/PVA复合水凝胶。考察不同配方下复合水凝胶的微观形貌变化,并对复合水凝胶的溶胀性能、压缩强度及热稳定性能进行研究。结果表明,CNFs与PEG对PVA水凝胶的微观形貌均有改善作用,加入PEG后形成的PEG/PVA凝胶产生明显的三维网络结构。当PEG与CNFs同时加入到PVA凝胶后形成的CNFs-PEG/PVA凝胶具有均匀的互穿孔洞结构,此时复合水凝胶的孔隙率最高((67.5±4.3)%),溶胀度最好(980%),且压缩强度较PVA水凝胶也有所提升。PEG对复合凝胶的热稳定性无影响,而加入CNFs后,CNFs-PEG/PVA复合凝胶的初始热分解温度从235℃上升至300℃,显著提高了PVA凝胶的热稳定性。     

Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel

Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an ‘one pot and one step’ in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M_n = 258 g mol⁻¹), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M_n = 475 g mol⁻¹) and (2-methoxyethoxy) ethyl methacrylate (MEO₂MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models.     

Novel chitosan hydrogel formed by ethylene glycol chitosan, 1,6-diisocyanatohexan and polyethylene glycol-400 for tissue engineering scaffold: in vitro and in vivo evaluation

Traditional chitosan hydrogels were prepared by chemical or physical crosslinker, and both of the two kinds of hydrogels have their merits and demerits. In this study, researchers attempted to prepare one kind of chitosan hydrogel by slightly crosslinker, which could combine the advantages of the two kinds of hydrogels. In this experiment, the crosslinker was formed by a reaction between the isocyanate group of 1,6-diisocyanatohexan and the hydroxyl group of polyethylene glycol-400 (PEG-400), then the crosslinker reacted with the amidine and the hydroxyl group of ethylene glycol chitosan to form the network structure. Physical properties of the hydrogel were tested by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and biodegradation. Biocompatibility was assessed by cell implantation in vitro and the scaffold was used as a cartilage tissue engineering scaffold to repair a defect in rabbit knee joints in vivo. FTIR results show the formation of a covalent bond during thickening of the ethylene glycol chitosan. SEM and degradation experiments showed that the ethylene glycol chitosan hydrogel is a 3-D, porous, and degradable scaffold. The hydrogel contained 2 % ethylene glycol chitosan and 10 μl crosslinker was selected for the biocompatibility experiment in vitro and in vivo. After chondrocytes were cultured in the ethylene glycol chitosan hydrogel scaffold for 1 week cells exhibited clustered growth and had generated extracellular matrix on the scaffold in vitro. The results in vivo showed that hydrogel-chondrocytes promoted the repair of defect in rabbits. Based on these results, it could be concluded that ethylene glycol chitosan hydrogel is a scaffold with excellent physicochemical properties and it is a promising tissue engineering scaffold.