Silicon dioxide/poly(vinyl alcohol) composite hydrogels with high mechanical properties and low swellability

Poly(vinyl alcohol) (PVA) hydrogels with tissue-like viscoelasticity, excellent biocompatibility, and hydrophilicity have been considered as promising cartilage replacement materials. However, the low mechanical properties of pure PVA hydrogels limit their applications for bearing complicated loads. Herein, we report silicon dioxide (SiO₂)/PVA composite hydrogels fabricated by fabricated cyclically freezing/thawing the aqueous mixture of PVA and methyltrimethoxysilane (MTMS). MTMS hydrolyzes and forms SiO₂ particles in situ to reinforce PVA hydrogel. Meanwhile, silanol group condenses with hydroxyl groups of PVA and chemically bonds with PVA. The resulting SiO₂/PVA hydrogels exhibit much better mechanical properties than bare PVA hydrogel. In addition, the composite hydrogels keep very low swellable property. This prepared composite hydrogels are promising in a variety of biomedical applications such as artificial articular cartilage, drug delivery, and biosensors. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46895.     

Super-tough hydrogels using ionically crosslinked networks

Alginate and polyacrylamide hydrogels were produced by a facile one-pot method with varied ionic crosslinkers in this article. These hydrogels display outstanding mechanical properties compared to the pristine polyacrylamide (PAAm) hydrogels. The alginate network is ionically crosslinked by multivalent cation, whereas N,N′-methylenebis (acrylamide) (MBAA) is used as covalent crosslinker for the PAAm network. Particularly, the obtained hydrogels by using trivalent cations (Fe³⁺ and Al³⁺) as crosslinkers are much stronger than that of using divalent cations (Ca²⁺ and Ba²⁺) as crosslinkers. In addition, with increasing concentration of cations, the compressive properties of gels are improved, whereas when the concentration is higher than 0.3 M, the compressive properties of gels are damaged due to mono-bindings. Interestingly, the hydrogels with higher chemical crosslinker concentration depicts better mechanical properties than those hydrogels with lower chemical crosslinker, which is different from that of common double network hydrogels. These hydrogels with excellent mechanical properties are promising candidates for biomedical application like load-bearing tissues. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48182.     

Lubrication behaviors of PVA-casted LSPEEK hydrogels in artificial cartilage repair

Poly(ether-ether-ketone) (PEEK) is a known bio-implant material due to its excellent mechanical properties. However, the challenging issue of high friction coefficient limits the PEEK applications. In this article, double-layered hydrogel material was obtained by laser processing, surface sulfonation, and poly(vinyl alcohol) (PVA) casting. Characterizations of FT-IR, XRD, SEM, and 3D-morphology demonstrate that PVA-LSPEEK hydrogel was achieved successfully. PVA-LSPEEK exhibits an extremely smooth surface with a roughness of 0.079 μm. And this hydrogel presents an excellent mechanical adhesion to PEEK substrate, forming a soft-hard structure. Tribological properties of PVA-LSPEEK are improved drastically when compared to the PEEK substrate. This innovative hydrogel material provides a potential application in articular cartilage defect repair. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47944.     

Recent advances in shear-thinning and self-healing hydrogels for biomedical applications

Shear-thinning and self-healing hydrogels are being investigated in various biomedical applications including drug delivery, tissue engineering, and 3D bioprinting. Such hydrogels are formed through dynamic and reversible interactions between polymers or polypeptides that allow these shear-thinning and self-healing properties, including physical associations (e.g., hydrogen bonds, guest–host interactions, biorecognition motifs, hydrophobicity, electrostatics, and metal–ligand coordination) and dynamic covalent chemistry (e.g., Schiff base, oxime chemistry, disulfide bonds, and reversible Diels–Alder). Their shear-thinning properties allow for injectability, as the hydrogel exhibits viscous flow under shear, and their self-healing nature allows for stabilization when shear is removed. Hydrogels can be formulated as uniform polymer and polypeptide assemblies, as hydrogel nanocomposites, or in granular hydrogel form. This review focuses on recent advances in shear-thinning and self-healing hydrogels that are promising for biomedical applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48668.     

Graphene Oxide Hybrid Supramolecular Hydrogels with Self‐Healable,Bioadhesive and Stimuli‐Responsive Properties and Drug Delivery Application

Self‐healable hydrogels are promising soft materials with great potential in biomedical applications due to their autonomous self‐repairing capability. Although many attempts are made to develop new hydrogels with good self‐healing performance, to integrate this characteristic along with other responsive multifunctions into one hydrogel still remains difficult. Here, a self‐healable hybrid supramolecular hydrogel (HSH) with tunable bioadhesive and stimuli‐responsive properties is reported. The strategy is imparting graphene oxide (GO) nanosheets and quadruple hydrogen bonding ureido‐pyrimidinone (UPy) moieties into a thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) polymer matrix. The obtained GO–HSH hydrogel shows rapid self‐healing behavior and good adhesion to various surfaces from synthetic materials to biological tissue. In addition, doxorubicin hydrochloride (DOX) release profiles reveal the dual thermo‐ and pH‐responsiveness of the GO–HSH hydrogel. The DOX‐loaded hydrogel can further directly adhere to titanium substrate, and the released DOX from this thin hydrogel coating remains biologically active and has high capability to kill tumor cells.     

Multifunctional mussel-inspired Gelatin and Tannic acid-based hydrogel with pH-controllable release of vitamin B12

Hydrogels have emerged to be an impeccable material for a large variety of applications over the past few decades. In the field of biomedical applications, remarkable progress has been observed in the effort of fabricating numerous hydrogel systems. In this work, gelatin and tannic acid-based stretchable and adhesive hydrogel has been synthesized to study the release behavior of vitamin B₁₂. Successful formation of the synthesized hydrogels was confirmed by Fourier transform infrared and X-ray diffraction analysis. The morphology of the surfaces and the cross section of such hydrogels were studied with Scanning electron microscopy analysis. Swelling behavior of our hydrogel was studied with Design Expert software. The maximum swelling of the hydrogel was found to be around 137 g/g. Adhesive property was demonstrated on various surfaces to observe the adhesiveness of the fabricated hydrogel. Blood compatibility study was also performed. The release behavior of vitamin B₁₂ was performed in two different pH media and it was found to have enhanced value in the fluid mimicking the intestine. This work provides a new prospect for designing hydrogels with stretchable and adhesive properties with pH-controllable drug delivery applications along with other promising applications in various fields of research.     

Highly Mechanical and Fatigue‐Resistant Double Network Hydrogels by Dual Physically Hydrophobic Association and Ionic Crosslinking

Double network (DN) hydrogels with high strength and toughness are considered as promising soft materials. Herein, a dual physically cross‐linked hydrophobic association polyacrylamide (HPAAm)/alginate‐Ca²⁺ DN hydrogel is reported, consisting of a HPAAm network and a Ca²⁺ cross‐linked alginate network. The HPAAm/alginate‐Ca²⁺ DN hydrogel exhibits excellent mechanical properties with the fracture stress of 1.16 MPa (3.0 and 1.7 times higher than that of HPAAm hydrogel and HPAAm/alginate hydrogel, respectively), fracture strain of 2604%, elastic modulus of 71.79 kPa, and toughness of 14.20 MJ m^?3. HPAAm/alginate‐Ca²⁺ DN hydrogels also demonstrate self‐recovery, notch‐insensitivity, and fatigue resistance properties without any external stimuli at room temperature through reversible physical bonds consisting of hydrophobic association and ionic crosslinking. As a result, the dual physical crosslinking would offer an avenue to design DN hydrogels with desirable properties for broadening current applications of soft materials.     

Photopolymerized hydrogel composites from poly(ethylene glycol) and hydroxyapatite for controlled protein delivery in vitro

The incorporation of hard particles into soft hydrogels can improve the mechanical properties and provide necessary bioactivity to the hydrogels for desired biomedical applications. Hydrogel composites containing hydroxyapatite (HA) are promising materials for orthopedic applications. In this study, injectable poly(ethylene glycol) (PEG) hydrogel precursor solutions containing HA particles and model protein bovine serum albumin (BSA) were synthesized in situ by photopolymerization. In vitro BSA release properties from the hydrogel composites containing various amounts of HA were investigated and discussed. Fourier transform infrared spectroscopy and scanning electron microscopy were employed to investigate the interaction between HA and the hydrogel network and the morphology of the hydrogel composites. It is found that PEG hydrogel composites containing HA sustained the release of BSA for at least 5 days and the presence of HA slowed down BSA release. Photopolymerized hydrogel composites containing HA may find potential use as a drug delivery matrix for orthopedic tissue engineering. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Photoluminescent and tough hydrogels from silk fibroin and polyacrylic acid complexed with europium

Biocompatible, tough, and photoluminescent hydrogels are highly desirable for biomedical applications in vivo. Herein, hybrid hydrogels prepared from silk fibroin (SF) and polyacrylic acid (PAA) and complexed with europium, named as SF-PAA-Eu³⁺ hydrogels, exhibit good comprehensive properties. Owing to the intensive molecular interactions among SF, PAA, and Eu³⁺, SF-PAA-Eu³⁺ hydrogels show a greatest tensile strength of 0.58 MPa, elongation of 443%, and work of fracture of 1.65 MJ/m. In vivo imaging experiment in a mouse subcutaneous implantation model revealed excellent and sustained photoluminescence of the SF-PAA-Eu³⁺ hydrogels for 24 h. The work provides a strategy for designing functional SF-based hydrogels for imaging applications in vivo.     

Effect of drug loading on the properties of temperature‐responsive polyester–poly(ethylene glycol)–polyester hydrogels

Hydrogels that can undergo gelation upon injection in vivo are promising systems for the site‐specific delivery of drugs. In particular, some thermo‐responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo‐responsive hydrogels based on poly(?‐caprolactone‐co‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(?‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti‐inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol^?1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol^?1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo‐responsive hydrogels can be substantial and depend on the drug. For applications such as intra‐articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case‐by‐case basis. © 2019 Society of Chemical Industry     

UV photopolymerized hydrogels with β-cyclodextrin moieties

Hydrophilic hydrogels based on poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) block copolymers have potential applications in drug delivery, tissue engineering and other biomedical devices due to their excellent biocompatibility and environmental sensitivity. However, they also exhibit some shortcomings in terms of swelling and mechanical properties as well as affinity for water-insoluble or hydrophobic drug molecules. To address these limitations, new polymeric hydrogels with β-cyclodextrin moieties were prepared by UV photo-polymerization of maleic anhydride-substituted β-CD (MAH-CD) and the block copolymer macromer from Pluronic F68 and poly(ɛ-caprolactone). Their swelling and dynamic rheological properties were investigated with respect to the effects of feed compositions. It was found that the swelling ratio, storage modulus and loss modulus of the resulting hydrogel increased with the increase of MAH-CD amount. Incorporation of MAH-CD resulted in strong viscoelastic system with dominating elastic behavior.     

Improving thermo-responsive hydrogel films by gamma rays and loading of Cu and Ag nanoparticles

This paper presents two modified copolymeric hydrogel films with thermo-responsiveness. The final films are hydrogels containing N-isopropylacrylamide, N-N-dimethylacrylamide, methyl methacrylate, and ethoxyethyl methacrylate. The incorporation of Ag and Cu in the smart hydrogel films endowed them with specific properties that could be useful in developing biological sensors, smart membranes, or flexible electronic components, which are proper for design and improvement on technology and biomedical applications. The films were synthesized in solution by gamma radiation at a dose rate of 10 kGy h⁻¹, and an absorbed dose of 50 kGy. The characterization was realized by different spectroscopic and microscopic techniques as FTIR-ATR, atomic force microscopy, SEM–EDX, TGA, and DSC. The hydrogel films were grafted with glycidyl methacrylate showing high resistance, biocompatibility, adequate adaptability, flexibility, in addition to the capacity of metal doping with silver and copper.     

Using Graphene-Based Materials for Stiff and Strong Poly(ethylene glycol) Hydrogels

Blood-contacting devices are increasingly important for the management of cardiovascular diseases. Poly(ethylene glycol) (PEG) hydrogels represent one of the most explored hydrogels to date. However, they are mechanically weak, which prevents their use in load-bearing biomedical applications (e.g., vascular grafts, cardiac valves). Graphene and its derivatives, which have outstanding mechanical properties, a very high specific surface area, and good compatibility with many polymer matrices, are promising candidates to solve this challenge. In this work, we propose the use of graphene-based materials as nanofillers for mechanical reinforcement of PEG hydrogels, and we obtain composites that are stiffer and stronger than, and as anti-adhesive as, neat PEG hydrogels. Results show that single-layer and few-layer graphene oxide can strengthen PEG hydrogels, increasing their stiffness up to 6-fold and their strength 14-fold upon incorporation of 4% w/v (40 mg/mL) graphene oxide. The composites are cytocompatible and remain anti-adhesive towards endothelial cells, human platelets and Staphylococcus aureus, similar to neat hydrogels. To the best of our knowledge, this is the first work to report such an increase of the tensile properties of PEG hydrogels using graphene-based materials as fillers. This work paves the way for the exploitation of PEG hydrogels as a backbone material for load-bearing applications.     

Conductive double-network hydrogel for a highly conductive anti-fatigue flexible sensor

Improving the mechanical properties of hydrogels is a prime example of their large-scale, diverse applications. Herein, we report a one-pot method for preparing a double network system hydrogel where the polyvinyl alcohol served as the first polymer backbone, acrylamide as the second network, and N, N′-Methylenebisacrylamide as the cross-linker, and the prepared hydrogels presented excellent mechanical properties with 1168% tensile strain and 598 kPa compressive strength. Through the metal–ligand bonds, an electrolyte solution containing Cu²⁺ was introduced into the hydrogel, which exhibits higher water retention than other electrolyte-containing hydrogels. Specially, the hydrogel was able to retain water for 8 h under extreme dry conditions at 60°C. The GF value was calculated to be 0.124 when the strain was 0%–64.2%. Furthermore, the hydrogel flexible sensor can detect changes in ambient temperature. When the ambient temperature rises, its relative resistance also tends to rise. In conclusion, this hydrogel sensor offers great potential applications in flexible sensors.     

Construction and evaluation of the hydroxypropyl methyl cellulose-sodium alginate composite hydrogel system for sustained drug release

We prepared a hydroxypropyl methyl cellulose-sodium alginate (HPMC-SA) composite hydrogel with a membrane covering the semi-interpenetrating network based on a semi-synthetic polymer hydroxypropyl methyl cellulose (HPMC) and a natural polymer sodium alginate (SA) by Ca²⁺ crosslinking and polyelectrolyte complexation with chitosan (CS) covering the hydrogel surface. The physiochemical properties of HPMC-SA hydrogels were evaluated by scanning electron microscopy, infrared spectrum, X-ray diffraction, and thermogravimetric analysis. The swelling ratio of the HPMC-SA composite hydrogel in simulated gastrointestinal fluid was measured. The drug release behavior of the HPMC-SA composite hydrogel for macro-molecular and small-molecule drugs was evaluated by using bovine serum albumin, metformin hydrochloride, and indomethacin as model drugs. The results showed that the HPMC-SA hydrogel had good water absorption and degradability, an increased swelling ratio of 55, and a prolonged time for maximum swelling degree of 50 h. Moreover, the hydrogel exhibited higher drug-loading capacity and improvements in the sustained release of bio-macromolecules, demonstrating its potential as a drug carrier for biomedical applications.     

Dual Cross‐Linked Hydrogels with High Strength,Toughness, and Rapid Self‐Recovery Using Dynamic Metal–Ligand Interactions

A dual cross‐linking design principle enables access to hydrogels with high strength, toughness, fast self‐recovery, and robust fatigue resistant properties. Imidazole (IMZ) containing random poly(acrylamide‐co‐vinylimidazole) based hydrogels are synthesized in the presence of Ni²⁺ ions with low density of chemical cross‐linking. The IMZ‐Ni²⁺ metal–ligand cross‐links act as sacrificial motifs to effectively dissipate energy during mechanical loading of the hydrogel. The hydrogel mechanical properties can be tuned by varying the mol% of vinylimidazole (VIMZ) in the copolymer and by changing the VIMZ/Ni²⁺ ratio. The resultant metallogels under optimal conditions (15 mol% VIMZ and VIMZ/Ni²⁺ = 2:1) show the best mechanical properties such as high tensile strength (750 kPa) and elastic modulus (190 kPa), combined with high fracture energy (1580 J m^?2) and stretchability (800–900% strain). The hydrogels are pH responsive and the extent of energy dissipation can be drastically reduced by exposure to acidic pH. These hydrogels also exhibit excellent anti‐fatigue properties (complete recovery of dissipated energy within 10 min after ten successive loading–unloading cycles at 400% strain), high compressive strength without fracture (17 MPa at 96% strain), and self‐healing capability due to the reversible dissociation and re‐association of the metal ion mediated cross‐links.     

Highly stretchable,ionic conductive and self-recoverable zwitterionic polyelectrolyte-based hydrogels by introducing multiple supramolecular sacrificial bonds in double network

Zwitterionic hydrogels have been explored for applications in electrochemical devices very recently due to their high water retention ability and interesting electrochemical properties. The use of zwitterionic hydrogels in devices requires them tough and recoverable or healable from fatigue damage. Herein, a double network zwitterionic hydrogel contains a reversible noncovalent interaction crosslinked polyvinyl alcohol (PVA) first network, together with a covalent/noncovalent hybrid crosslinked acrylamide and sulfobetaine methacrylate copolymer (P(AM-co-SBMA)) second network, was fabricated by a simple two-steps methods of copolymerization and freezing/thawing. The reversible hydrogen bonds, crystalline domain, and electrostatic interactions in the double networks work as sacrificial bonds to dissipate energy and toughen the materials when hydrogel deforms. The broken bonds can reform upon unloading endowing the recovery of hydrogels' properties with the assistance of the elastic covalent network. The optimal hydrogels are highly stretchable (fracture strain 970%), tough (fracture toughness 693 kJ m⁻³), rapidly recoverable (65% toughness recovery and 75% stiffness recovery after resting 5 min at room temperature) and with widely tunable mechanical properties by multibond crosslinking. Meanwhile, the zwitterionic counterions of SBMA moieties endow the tough and recoverable hydrogels extremely high intrinsic ionic conductivities (7.49 S m⁻¹) at room temperature. This work not only provides a simple strategy for fabricating tough and recoverable zwitterionic hydrogels but also demonstrates multifunctional properties of the zwitterionic hydrogels, which possess a great potential to fulfill flexible devices applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47783.     

Self-healing and conductivity of chitosan-based hydrogels formed by the migration of ferric ions

The currently reported self-healing hydrogels have problems of low mechanical strength, single performance, and poor self-healing efficiency, which greatly limit their applications. Here, through adding N-carboxyethyl chitosan to acrylic-Fe³⁺ system, the self-healing physically crosslinked hydrogels were prepared via in situ free radical polymerization, which have excellent self-healing ability and mechanical properties. The maximum tensile strength and elongation at break of the hydrogels can reach up to 280 KPa and 1900%, respectively. Owing to the reversibility of coordination, self-healing efficiency of the hydrogels can reach 98% in 2.5 h. Moreover, the hydrogels also have good conductivity due to the migration of Fe³⁺. This strategy can broaden the applications of chitosan-based self-healing hydrogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47885.     

Synthesis of novel thermo‐ and redox‐sensitive polypeptide hydrogels

Multi‐responsive hydrogels have recently received considerable attention for bioapplications. Here, novel temperature‐ and redox‐responsive polypetide hydrogels have been developed. Thermo‐sensitive hydrogels based on poly(ethyleneglycol)‐block ‐poly(γ‐propargyl‐l ‐glutamate) (PEG‐PPLG ) were first synthesized by the ring opening polymerization of γ‐propargyl‐l ‐glutamate N ‐carboxyanhydride (PLG‐NCA ) with amino group terminated PEG monomethyl ether (mPEG‐NH₂ ) as macroinitiator and were then functionalized via the ‘thiol‐yne’ click reaction between the propargyl pendents and the thiol‐containing 1‐propanethiol. The sol ? gel phase transition of the obtained copolymer aqueous solution in response to temperature change was studied. The mass loss of the hydrogel in vitro was accelerated in the presence of H₂O₂ , exhibiting a redox‐responsive property. Further, the methyl thiazolyl tetrazolium viability results revealed that this polypetide hydrogel has excellent biocompatibility, presenting potential applications in the biomedical field. © 2016 Society of Chemical Industry     

Self-assembly and metal ions-assisted one step fabrication of recoverable gelatin hydrogel with high mechanical strength

ABSTRACT

Gelatin hydrogel has been widely applied in bio-applications due to their good biocompatibility and high water content. However, poor mechanical properties of gelatin hydrogel greatly limit their application. Here we present a facile one-step soaking method to fabricate a recoverable gelatin hydrogel with high mechanical property, which is based on hydrogen bonds and metal ionic interaction. The mechanical properties of gelatin hydrogels can be tuned with different metal ions, temperatures and soaking times. Especially, gelatin-Fe³⁺ hydrogel can reach to 65 MPa compression stress with the compressive strain over 99% and possess good fatigue resistance under cyclic loadings. Besides, hydrogels crosslinked with metal ions show better antibacterial ability against Escherichia coli and Staphylococcus aureus. This work suggested an alternative for the design of tough gelatin-based hydrogels with desirable properties, which may hold promising for potential bio-applications under physiological conditions.