Cationic Modified PVA Hydrogels Provide Low Friction and Excellent Mechanical Properties for Potential Cartilage and Orthopedic Applications

Poly(vinyl alcohol) (PVA) hydrogel is a promising candidate for articular cartilage repair yet restrained by its mechanical strength and tribological property. Current work reports a newly designed PVA-based hydrogel modified by glycerol (g), bacterial cellulose (BC), and a cationic polymer poly (diallyl dimethylammonium chloride) (PDMDAAC), which is a novel cationic strengthening choice. The resultant PVA-g-BC-PDMDAAC hydrogel proves the effectiveness of this modification scheme, with a confined compressive modulus of 19.56 MPa and a friction coefficient of 0.057 at a joint-equivalent load and low sliding speed. The water content, swelling property, and creep behavior of this hydrogel are also within a cartilage-mimetic range. The properties of PVA-based hydrogels before PDMDAAC addition are likewise studied as a cross-reference. Besides, PDMDAAC-modified PVA hydrogel realizes ideal mechanical and lubrication properties with a relatively low PVA concentration (10 wt.%) and facile fabrication process, which lays a foundation for mass production and marketization in the future.     

Current Intelligent Injectable Hydrogels for In Situ Articular Cartilage Regeneration

Abstract

A high number of sport injuries result in damage to articular cartilage, a tissue type with poor self-healing capacity. Articular cartilage tissue is a sophisticated hydrogel, which contains 80% water and possesses strong mechanical properties. For this reason, synthetic hydrogels are thought to be an optimal material for cartilage regeneration. In the last decade, more than 2,000 research papers pertaining to “hydrogel and cartilage” have been published. Due to its biomimetic properties and user-friendly nature, especially in the field of minimal invasive surgery, intelligent injectable hydrogel have gradually become a focal point in cartilage research in recent years. In this review, we systematically summarize current “state-of-the-art” manufacture technologies of injectable hydrogels including ion-induced, thermo-induced, non-induced chemical, and light-induced crosslinking. We also review current strategies for designing intelligent injectable hydrogels, such as component-based, mechanical property-based and structure-based intelligent design to simulate the natural articular cartilage. Lastly, the applications of intelligent injectable hydrogels for cartilage regeneration are presented, and their outlooks for future clinical translation is dicussed.     

层状水凝胶仿生软骨的制备与性能

采用超声分散、高压加热共融、冷冻-熔融和γ射线辐照交联成型工艺制备层状水凝胶仿生软骨材料, 系统讨论了PVP添加量和辐照剂量对材料的凝胶含量、晶态结构及抗压缩弹性模量的影响, 观察和研究了层状水凝胶的微观结构. 研究结果表明, 随着PVP的质量分数(0-40%)和辐照剂量(0-60 kGy)的增加, 层状水凝胶的凝胶含量呈上升趋势; 其晶态结构在质量分数为20%的PVP和10 kGy辐照剂量下最完善; 其力学性能在质量分数为20%的PVP和20 kGy辐照剂量下最佳; PVP的加入改善了水凝胶的微观形貌, 有利于材料表面润滑性能的提高; 层状水凝胶层间渗透结合, 自然过渡, 形成结构良好的仿生软骨材料.     

Swelling studies of copolymeric acrylamide/crotonic acid hydrogels as carriers for agricultural uses

In this study, highly swollen acrylamide/crotonic acid hydrogels (in a rod form) containing some inorganic salts such as ammonium nitrate, potassium nitrate and ammonium sulphate used as fertilizer, an agricultural drug such as Dalapon (sodium 2,2‐dichloropropionate) and two crosslinkers such as ethylene glycol dimethacrylate and 1,4‐butandiol dimethacrylate were prepared by copolymerization of acrylamide and crotonic acid with γ‐radiation. As a result of swelling tests, the influence of γ‐ray dose and relative content of crotonic acid on the swelling properties, the diffusional behavior of water, diffusion coefficients and network properties of the hydrogel systems were examined. Acrylamide/crotonic acid hydrogels containing these salts and agricultural drug were swollen in the range 2045–400% in water, while polyacrylamide hydrogels swelled in the range 660–700%. Water intake of hydrogels followed a nonFickian‐type diffusion. Copyright © 2000 John Wiley & Sons, Ltd.     

Zr(IV)‐Crosslinked Polyacrylamide/Polyanionic Cellulose Composite Hydrogels with High Strength and Unique Acid Resistance

Recently, metal coordination has been widely utilized to fabricate high‐performance hydrogels, but conventional metal‐based hydrogels face some drawbacks, such as staining or acid lability. In the present study, a novel kind of colorless Zr(IV)‐crosslinked polyacrylamide/polyanionic cellulose (PAM/PAC) composite hydrogel with unique acid resistance was constructed via acrylamide polymerization in a PAC solution, followed by posttreatment in a zirconium oxychloride (ZrOCl₂) solution. The prepared gels were characterized in terms of Fourier transform infrared spectroscopy, scanning electron microscopy, and tensile and compressive mechanics, as well as acid resistance. Inside the gels, the synergistic action of hydrogen bonding and Zr(IV) coordination is responsible for their improved mechanical properties and good energy dissipation ability. One hydrogel with nearly 90 wt % of water content can sustain approximately 5 MPa of compression stress at 90% strain without damage. Both microscopic network structures and macroscopic mechanics demonstrate facile adjustability via changing the PAC dosages in polymerization and/or ZrOCl₂ concentrations in posttreatment. Moreover, the gels present unexpected acid resistance due to the strong Zr(IV) coordination with PAC, demonstrating their potential application as hydrogel electrolytes in supercapacitors. The current work provides a new approach to fabricate metal coordination‐based high strength, colorless hydrogels with acid resistance. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 981–991     

Inelastic behaviour of bacterial cellulose hydrogel: In aqua cyclic tests

Hydrogels are finding increasingly broad use, especially in biomedical applications. Their complex structure – a low-density network of microfibrils – defines their non-trivial mechanical behaviour. The focus of this work is on test-based quantification of mechanical behaviour of a bacterial cellulose (BC) hydrogel exposed to cyclic loading. Specimens for the tests were produced using Gluconacetobacter xylinus ATCC 53582 and tested in aqua under uniaxial cyclic loading conditions in a displacement-controlled regime. Substantial microstructural changes were observed in the process of deformation. A combination of qualitative microstructural observations with quantitative force-displacement relations allowed identification of main deformation mechanisms, confirming inelastic behaviour of the BC hydrogel under a loading-unloading-reloading regime. Elastic deformation was accompanied by non-elastic (viscoplastic) deformation in both tension and compression. This study also aims to establish a background for micromechanical modelling of overall properties of BC hydrogels.     

Rational Design and Development of Anisotropic and Mechanically Strong Gelatin‐Based Stress Relaxing Hydrogels for Osteogenic/Chondrogenic Differentiation

Rational design and development of tailorable simple synthesis process remains a centerpiece of investigational efforts toward engineering advanced hydrogels. In this study, a green and scalable synthesis approach is developed to formulate a set of gelatin‐based macroporous hybrid hydrogels. This approach consists of four sequential steps starting from liquid‐phase pre‐crosslinking/grafting, unidirectional freezing, freeze‐drying, and finally post‐curing process. The chemical crosslinking mainly involves between epoxy groups of functionalized polyethylene glycol and functional groups of gelatin both in liquid and solid state. Importantly, this approach allows to accommodate different polymers, chitosan or hydroxyethyl cellulose, under identical benign condition. Structural and mechanical anisotropy can be tuned by the selection of polymer constituents. Overall, all hydrogels show suitable structural stability, good swellability, high porosity and pore interconnectivity, and maintenance of mechanical integrity during 3‐week‐long hydrolytic degradation. Under compression, hydrogels exhibit robust mechanical properties with nonlinear elasticity and stress‐relaxation behavior and show no sign of mechanical failure under repeated compression at 50% deformation. Biological experiment with human bone marrow mesenchymal stromal cells (hMSCs) reveals that hydrogels are biocompatible, and their physicomechanical properties are suitable to support cells growth, and osteogenic/chondrogenic differentiation, demonstrating their potential application for bone and cartilage regenerative medicine toward clinically relevant endpoints.     

Cellulose–halloysite nanotube composite hydrogels for curcumin delivery

Halloysite nanotubes (HNTs) were added to cellulose NaOH/urea solution to prepare composite hydrogels using epichlorhydrine crosslinking at an elevated temperature. The shear viscosity, mechanical properties, microstructure, swelling properties, cytocompatibility, and drug delivery behavior of the cellulose/HNT composite hydrogels were investigated. The viscosity of the composite solution increases with the addition of HNT. The compressive mechanical properties of composite hydrogels are significantly improved compared with pure cellulose hydrogel. The compressive strength of the composite hydrogels with 66.7% HNTs is 128 kPa, while that of pure cellulose hydrogel is only 29.8 kPa in compressive strength. Rheological measurement suggests the resistance to deformation is improved for composite hydrogels. X-ray diffraction and Fourier transform infrared spectroscopy show that the crystal structure and chemical structure of HNT are not changed in the composite hydrogels. Hydrogen bonding interactions between HNT and cellulose exist in the composites. A porous structure of the composite hydrogels with pore size of 200–400 μm was found by scanning electron microscopy. The addition of HNT leads to decreased swelling ratios in NaCl solution and pure water for the composite hydrogels. Cytotoxicity assays show that the cellulose/HNT composite hydrogels have a good biocompatibility with MC3T3-E1 cells and MCF-7 cells. Curcumin is further loaded into the composite hydrogel via physical adsorption. The curcumin-loaded composite hydrogels show a strong inhibition effect on the cancer cells. All the results illustrate that the cellulose/HNT composite hydrogels have promising applications such as anticancer drug delivery systems and anti-inflammatory wound dressings.     

Evaluation of the degree of cross-linking of cellulose-based superabsorbent hydrogels: a comparison between different techniques

Three different techniques have been applied to the evaluation of the degree of cross-linking of superabsorbent cellulose-based hydrogels obtained from water solutions of carboxymethylcellulose sodium salt (CMCNa) and hydroxyethylcellulose (HEC), chemically cross-linked with divinyl sulfone. These polyelectrolyte hydrogels are biodegradable and have the same sorption capacity as acrylate-based superabsorbents on the market. A ¹³C solid state NMR analysis was carried out on dry samples of hydrogel to obtain the degree of cross-linking, an important parameter that affects the swelling and mechanical properties of a hydrogel. Dynamic mechanical analysis was performed during the hydrogel cross-linking using a parallel plate rheometer under oscillatory deformations in order to monitor the evolution of the hydrogel viscoelastic properties during the synthesis. The value of |G*| and the slope of the stress-deformation ratio plots from uniaxial compression tests were used to evaluate the elastically effective degree of cross-linking according to classical rubber elasticity theory. Moreover, a dynamic mechanical analysis was carried out on cross-linked hydrogels at different degrees of swelling in order to investigate the influence of the swelling on the mechanical properties and the application of rubber elasticity theory to swollen hydrogels.     

Reinforcement of Self‐Healing Polyacrylic Acid Hydrogel with Acrylamide Modified Microcrystalline Cellulose†

Self‐healing hydrogel such as polyacrylic acid (PAA) hydrogel has attracted increasing attention based on its promising potential applications. However, it usually suffers from low strength especially as mechanical device. Herein, a commercial microcrystalline cellulose (MCC) was modified with acrylamide to graft polyacrylamide (PAM) chains on the particle surface. The acrylamide‐modified MCC (AM‐MCC) was then dispersed in monomer solution of acrylic acid to prepare composite hydrogel. The mechanical properties of the obtained composite hydrogels and the self‐healed hydrogels were carefully measured by compressive and tensile tests, and by dynamic mechanical analysis. Our results demonstrate that introduction of a small amount of AM‐MCC such as 3 wt% can not only reinforce the original hydrogel and the healed hydrogel markedly, but also improve self‐healing efficiency obviously. The analyses indicate that in addition to the reversible multi‐interactions such as hydrogen bonding and ionic interactions, the entanglements between the PAA chains of the hydrogel matrix and the PAM chains grafted on the MCC particles have also played an important role on the improvement in mechanical performances and the healing ability of the hydrogel. Moreover, the responsiveness to exterior ion has been tested to indicate potential application of the composite hydrogel as self‐healable sensor.     

Preparation of interpenetrating polymer network composed of poly(ethylene glycol) and poly(acrylamide) hydrogels as a support of enzyme immobilization

Poly(ethylene glycol)(PEG)‐based interpenetrating polymeric network (IPN) hydrogels were prepared for the application of enzyme immobilization. Poly(acrylamide)(PAAm) was chosen as the other network of IPN hydrogel and different concentration of PAAm networks were incorporated inside the PEG hydrogel to improve the mechanical strength and provide functional groups that covalently bind the enzyme. Formation of IPN hydrogels was confirmed by observing the weight per cent gain of hydrogel after incorporation of PAAm network and by attenuated total reflectance/Fourier transform infrared (ATR/FTIR) analysis. Synthesis of IPN hydrogels with higher PAAm content produced more crosslinked hydrogels with lower water content (WC), smaller M_c and mesh size, which resulted in enhanced mechanical properties compared to the PEG hydrogel. The IPN hydrogels exhibited tensile strength between 0.2 and 1.2 MPa while retaining high levels of hydration (70–81% water). For enzyme immobilization, glucose oxidase (GOX) was immobilized to PEG and IPN hydrogel beads. Enzyme activity studies revealed that although all the hydrogels initially had similar enzymatic activity, enzyme‐immobilizing PEG hydrogels lost most of the enzymatic activity within 2 days due to enzyme leaching while IPN hydrogels maintained a maximum 80% of the initial enzymatic activity over a week due to the covalent linkage between the enzyme and amine groups of PAAm. Copyright © 2008 John Wiley & Sons, Ltd.     

Micromechanical Properties of Microstructured Elastomeric Hydrogels

Local, micromechanical environment is known to influence cellular function in heterogeneous hydrogels, and knowledge gained in micromechanics will facilitate the improved design of biomaterials for tissue regeneration. In this study, a system comprising microstructured resilin‐like polypeptide (RLP)–poly(ethylene glycol) (PEG) hydrogels is utilized. The micromechanical properties of RLP‐PEG hydrogels are evaluated with oscillatory shear rheometry, compression dynamic mechanic analysis, small‐strain microindentation, and large‐strain indentation and puncture over a range of different deformation length scales. The measured elastic moduli are consistent with volume averaging models, indicating that volume fraction, not domain size, plays a dominant role in determining the low strain mechanical response. Large‐strain indentation under a confocal microscope enables the visualization of the microstructured hydrogel micromechanical deformation, emphasizing the translation, rotation, and deformation of RLP‐rich domains. The fracture initiation energy results demonstrate that failure of the composite hydrogels is controlled by the RLP‐rich phase, and their independence with domain size suggested that failure initiation is controlled by multiple domains within the strained volume. This approach and findings provide new quantitative insight into the micromechanical response of soft hydrogel composites and highlight the opportunities in employing these methods to understand the physical origins of mechanical properties of soft synthetic and biological materials.     

Dendritic macromers for hydrogel formation: Tailored materials for ophthalmic,orthopedic, and biotech applications

Dendritic macromolecules are well‐defined highly branched macromolecules synthesized via a divergent or convergent approach. A salient feature of the macromolecules described herein, and a goal of our research effort, is to prepare dendritic macromolecules suitable for in vitro and in vivo use by focusing on biocompatible building blocks and biodegradable linkages. These dendritic macromolecules can be subsequently crosslinked to form hydrogels using a photochemical acrylate‐based or a chemical ligation strategy. The properties—mechanical, swelling, degradation, and so forth—of the hydrogels can be tuned by altering the composition, crosslinking chemistry, wt %, generation number and so forth. The utility and diverse applicability is demonstrated through successful use of these hydrogels in three unique applications: hydrogel adhesives for repairing corneal wounds, hydrogel scaffolds for cartilage tissue engineering, and hydrogel reaction chambers for high throughput screening of molecular recognition events. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 383–400, 2008.     

Hybrid Vesicles Enable Mechano-Responsive Hydrogel Degradation

Stimuli-responsive hydrogels are intriguing biomimetic materials. Previous efforts to develop mechano-responsive hydrogels have mostly relied on chemical modifications of the hydrogel structures. Here, we present a simple, generalizable strategy that confers mechano-responsive behavior on hydrogels. Our approach involves embedding hybrid vesicles, composed of phospholipids and amphiphilic block copolymers, within the hydrogel matrix to act as signal transducers. Under mechanical stress, these vesicles undergo deformation and rupture, releasing encapsulated compounds that can control the hydrogel network. To demonstrate this concept, we embedded vesicles containing ethylene glycol tetraacetic acid (EGTA), a calcium chelator, into a calcium-crosslinked alginate hydrogel. When compressed, the released EGTA sequesters calcium ions and degrades the hydrogel. This study provides a novel method for engineering mechano-responsive hydrogels that may be useful in various biomedical applications.     

聚乙烯醇硫酸钾水凝胶电机械化学行为研究

通过将交联聚乙烯醇硫酸酯化的方法制备了一种新型电刺激响应性聚乙烯醇硫酸钾(PVSK)智能水凝胶,并探讨了溶液离子强度和pH对PVSK水凝胶的溶胀吸水率、机械性能以及电机械化学行为的影响.结果表明,制备的PVSK水凝胶的平衡溶胀比随NaCl溶液离子强度的增大而减小,在pH2.39～10.83范围内基本不受溶液pH的影响;经不同离子强度和pH的NaCl溶液充分溶胀的PVSK水凝胶具有良好的机械性能,在非接触的直流电场作用下,该水凝胶向电场负极弯曲,凝胶的弯曲速度和弯曲偏转量随外加电场强度的增加而增大,随NaCl溶液离子强度的增大出现临界最大值,但不随溶液pH(2.08～10.53)的改变而改变;在循环电场作用下,PVSK水凝胶的电机械化学行为具有良好的可逆性.     

Adsorption of bovine serum albumin to acrylamide–itaconic acid hydrogels

In this study, acrylamide–itaconic acid hydrogels containing different amounts of itaconic acid prepared by irradiating with γ radiation are discussed. They have been used in experiments of swelling, diffusion and bovine serum albumin (BSA) adsorption. Maximum and minimum swellings were observed with water (1520%) and BSA (890%), respectively. Diffusion of water, NaCl and BSA within hydrogels were found to be non-Fickian in character. In the experiments of BSA adsorption, type III adsorption was found. The hydrogel prepared with 60 mg itaconic acid and irradiated at 2.00 kGy was found to be the best adsorption system for BSA. The adsorption capacity of acrylamide–itaconic acid hydrogel was found to exceed that of acrylamide hydrogel by more than 80–100%.     

Green synthesis and swelling behavior of Ag-nanocomposite semi-IPN hydrogels and their drug delivery using Dolichos biflorus Linn

Acrylic-based hydrogels with great potentials for usage in medical area were principally synthesized as per two strategies. The first involved reaction containing silver nitrate to yield silver nanoparticles (AgNPs) where Dolichos biflorus Linn acted as both reducing agent and stabilizing for green synthesized AgNPs was added to the reaction medium to establish reduction of Ag+ to AgNPs. The second strategy entailed preparation of nanosilver composite hydrogel that is carried out by free radical polymerization reaction in presence of Sodium Alginate and acrylamide (AAm) under the same conditions. In both strategies, factors affecting the characterization of AgNPs-loaded hydrogels were studied. Analysis and characterization of the so obtained hydrogels were performed through monitoring swelling behavior, FTIR spectroscopy, SEM, EDX, UV–Vis spectrophotometer, XRD, and TEM. Results indicate that modifying AAm and silver ion can improve swelling properties of the resultant nanocomposite hydrogel. pH response of this nanocomposite hydrogel in different pH made it suitable for drug delivery applications.     

高强度PAMPS-PAAm互穿网络凝胶及其溶胀性能

通过考察不同单体浓度或离子强度下凝胶的力学性能和溶胀特性,对聚2-丙烯酰胺-2-甲基丙磺酸(PAMPS)与聚丙烯酰胺(PAAm)形成的互穿网络凝胶的高强度性能和作用机理进行了研究.结果表明:PAMPS-PAAm互穿网络凝胶的力学强度对c(AMPS)存在一个最佳值(1 mol/L),且随c(AAM)的增大而显著增大(0.5～4 mol/L).当c(AMPS)=1 mol/L、c(AAM)＝4 mol/L时,互穿网络凝胶的最大抗压强度达6.46 MPa;改变凝胶体系内水的离子强度,PAMPS-PAAm凝胶在0.25 mol/kg离子强度时的抗压强度与纯水状态下相比增加了29%.     

Semi‐interpenetrating polymer networks composed of poly(N‐isopropyl acrylamide) and polyacrylamide hydrogels

Three series of semi‐interpenetrating polymer networks, based on crosslinked poly(N‐isopropyl acrylamide) (PNIPA) and 1 wt % nonionic or ionic (cationic and anionic) linear polyacrylamide (PAAm), were synthesized to improve the mechanical properties of PNIPA gels. The effect of the incorporation of linear polymers into responsive networks on the temperature‐induced transition, swelling behavior, and mechanical properties was studied. Polymer networks with four different crosslinking densities were prepared with various molar ratios (25:1 to 100:1) of the monomer (N‐isopropyl acrylamide) to the crosslinker (methylenebisacrylamide). The hydrogels were characterized by the determination of the equilibrium degree of swelling at 25 °C, the compression modulus, and the effective crosslinking density, as well as the ultimate hydrogel properties, such as the tensile strength and elongation at break. The introduction of cationic and anionic linear hydrophilic PAAm into PNIPA networks increased the rate of swelling, whereas the presence of nonionic PAAm diminished it. Transition temperatures were significantly affected by both the crosslinking density and the presence of linear PAAm in the hydrogel networks. Although anionic PAAm had the greatest influence on increasing the transition temperature, the presence of nonionic PAAm caused the highest dimensional change. Semi‐interpenetrating polymer networks reinforced with cationic and nonionic PAAm exhibited higher tensile strengths and elongations at break than PNIPA hydrogels, whereas the presence of anionic PAAm caused a reduction in the mechanical properties. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3987–3999, 2004     

Synthesis and burst strength of water‐swollen immunoisolatory tubules

A series of amphiphilic hydrogel tubules have been prepared by copolymerizing/crosslinking hydrophilic poly(dimethylacrylamide) segments with hydrophobic di‐, tri‐, and octamethacrylate‐telechelic polyisobutylene crosslinkers, and their elastic modulus and burst strength in the water‐swollen state were investigated. Because the burst characteristics of hydrogels have not yet been quantitatively investigated, equipment was designed and built to generate fundamental insight into the burst properties of thin‐walled (200–250 μm) narrow lumen (2–3 mm i.d.) water‐swollen tubules. The theory developed to describe quantitatively the inflation behavior of thin‐walled rubber tubules was adapted to treat our experimental observations. Changes in the burst strength, elastic modulus, and expansion during the inflation of hydrogel tubules were interpreted in terms of the molecular weight of the hydrophilic segments between crosslinking sites (M_{c,hydrophilic}), which in turn was calculated according to the rubber elasticity theory. According to these investigations, the burst strength of our water‐swollen amphiphilic tubules is in the 0.2–0.5 MPa range, which is sufficient for implantation and immunoisolatory applications. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2075–2084, 2002