A Review: Tailor-made Hydrogel Structures (Classifications and Synthesis Parameters)

Hydrogels are being prepared for use in a wide variety of applications ranging from medicines, tissue engineering, superabsorbents, controlled release of drugs & fertilizers, and oil absorbers etc. This review highlights hydrogel structure and their different classifications under various heads. It also discusses various routes to obtain tailormade hydrogels by polymerizing a combination of two or more monomers with proper type of crosslinks in order to obtain desired properties in the resulting hydrogel. Novel hydrogel configurations like microgels and nanogels, slide ring gels, double network hydrogels and nanocomposite gels have also been reviewed.     

NVCL-Based Hydrogels and Composites for Biomedical Applications: Progress in the Last Ten Years

Hydrogels consist of three-dimensionally crosslinked polymeric chains, are hydrophilic, have the ability to absorb other molecules in their structure and are relatively easy to obtain. However, in order to improve some of their properties, usually mechanical, or to provide them with some physical, chemical or biological characteristics, hydrogels have been synthesized combined with other synthetic or natural polymers, filled with inorganic nanoparticles, metals, and even polymeric nanoparticles, giving rise to composite hydrogels. In general, different types of hydrogels have been synthesized; however, in this review, we refer to those obtained from the thermosensitive polymer poly(N-vinylcaprolactam) (PNVCL) and we focus on the definition, properties, synthesis techniques, nanomaterials used as fillers in composites and mainly applications of PNVCL-based hydrogels in the biomedical area. This type of material has great potential in biomedical applications such as drug delivery systems, tissue engineering, as antimicrobials and in diagnostic and bioimaging.     

具有快速响应特性的环境响应型智能水凝胶的研究进展

环境响应智能水凝胶应用于化学传感器、化学微阀、人造肌肉、药物控释载体、物质分离等领域时常常需要快速响应特性,提高智能水凝胶的响应速率成为了智能水凝胶研究领域的重要课题之一。本文主要综述了具有快速响应特性的环境响应智能水凝胶的构建策略与方法,重点介绍了3类具有不同结构的快速响应型智能水凝胶,即具有多孔结构的快速响应智能水凝胶、具有梳状结构的快速响应智能水凝胶以及具有微球复合结构的快速响应智能水凝胶。     

Neutron transmission and quasi-elastic neutron scattering in polymer hydrogels

Investigations of hydrogels with high water contents have recently acquired special significance. Hydrogels are crosslinked three-dimensional networks of water-soluble macromolecules saturated by water or water solutions of different substances. The interest in examination the fundamental physical properties for such systems is related to their numerious applications. Using neutron transmission and quasi-elastic neutron scattering (QENS), the mass transfer and self-diffusion processes of water and water solutions in gelatin and poly(acrylamide) hydrogels were studied. It was shown that the macroscopic liquid flow through network of quasi-porous polymer gels at relatively low pressure gradients as well as self-diffusion of water and water solutions in the above systems are adequately described by “effective medium” approach. QENS data were also interpreted using an approach that accounts for the hierarchy of time scales of molecular motions: slow collective motions of liquid molecules contained in Lagrange's clusters and rapid single-particle motions. The friction and self-diffusion coefficient data were used to estimate the effective pore sizes of gels at different polymer concentrations as well as the mean Lagrange's cluster sizes.     

Synthetic hydrogels: Synthesis,novel trends,and applications

Hydrogels have been generated and explored for use in various applications. The main objective of this comprehensive review is to collate the fundamental concepts of hydrogels, and elaborate on knowledge gaps, and to provide a perspective on the future directions. This review includes details of constituent molecules (monomers, cross-linkers, composite materials, etc.) and the methods used to prepare polymer networks. Moreover, the review highlights modifications of hydrogels that introduce new properties or enhance the existing features to suit the desired applications and challenges of synthetic polymer hydrogels. The other important topics covered in this review are the synthesis and applications of 3D printed hydrogels, nanocomposite hydrogels, injectable hydrogels, and self-healing hydrogels.     

Cyclodextrin-Containing Hydrogels: A Review of Preparation Method,Drug Delivery,and Degradation Behavior

Hydrogels possess porous structures, which are widely applied in the field of materials and biomedicine. As a natural oligosaccharide, cyclodextrin (CD) has shown remarkable application prospects in the synthesis and utilization of hydrogels. CD can be incorporated into hydrogels to form chemically or physically cross-linked networks. Furthermore, the unique cavity structure of CD makes it an ideal vehicle for the delivery of active ingredients into target tissues. This review describes useful methods to prepare CD-containing hydrogels. In addition, the potential biomedical applications of CD-containing hydrogels are reviewed. The release and degradation process of CD-containing hydrogels under different conditions are discussed. Finally, the current challenges and future research directions on CD-containing hydrogels are presented.     

快速响应智能水凝胶的研究进展

能响应外界刺激的智能水凝胶由于其特有的响应性,具有广泛的应用前景。做为药物控制释放载体的智能水凝胶,通常由于差的机械性能和慢的响应速度限制了它的实际应用。近年来,许多研究工作者围绕提高智能水凝胶的响应速度作出了大量的工作。综述了近年来提高智能水凝胶响应速度的研究进展。     

Alginate: properties and biomedical applications

Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.     

Hydrogels based on copolymers of 2‐hydroxyethylmethacrylate and 2‐hydroxyethylacrylate as a delivery system for proteins: Interactions with lysozyme

Hydrogels have attracted considerable attention due to numerous applications, in particular as contact lenses and carriers for sustained drug delivery. The aim of the present work is to characterize the interactions of copolymer hydrogels consisted of 2‐hydroxyethylmethacrylate (HEMA) and 2‐hydroxyethylacrylate (HEA) with a small protein (lysozyme) and to assess the potential applications of these hydrogels as a drug delivery system for sustained release of protein‐based therapeutics. Physicochemical properties of protein‐loaded hydrogels, as well as lysozyme in vitro loading and release and the conformation of the protein released from hydrogels were studied. The effect of copolymer composition on the protein deposition on hydrogels and protein aggregation in the presence of hydrogels was also assessed. The results show that introduction of HEA into the copolymeric hydrogels enhances their suitability as a delivery system for proteins. Copolymerisation of HEMA and HEA allows controlling the physicochemical properties of hydrogels and the protein release rate. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44768.     

Synthesis,characterization, and in vitro cytotoxicity of chitosan hydrogels containing nanogold

Hydrogels due to their unique properties are characterized by a wide range of applications. In presented research a series of hydrogel based on chitosan and modified with nanogold have been prepared by photopolymerization. Based on the research it can be concluded that presented hydrogels are interesting materials that can play a key role in medicine. They are characterized by biocompatibility to simulated physiological fluids and do not show any cytotoxicity to the dermal cells. Furthermore, they are characterized by relatively high sorption capacity. These results show the possibility of the potential use of these hydrogels for biomedical purposes.     

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.     

Effects of pore morphology and size on antimicrobial activity of chitosan/poly(ethylene glycol) diacrylate macromer semi‐IPN hydrogels

The objective of this study was to obtain antibacterial active chitosan/poly(ethylene glycol) diacrylate macromere (CS/PEGM) semi‐IPN hydrogels near a neutral pH level by changing their pore size and morphology. These hydrogels were prepared from CS and PEGM with different molecular weights in the presence of pore‐forming agents, poly (ethylene glycol) (PEG) or sodium bicarbonate (NaHCO₃), by using two different initiator system, namely chemical or UV. A combination of CS with PEG or NaHCO₃ in the presence of PEGM could be able to create desired pore formation in both initiator systems. The antibacterial activity of hydrogels changed with the molecular weight (g/mol) of PEGM in the order 2000>400>8000. A chemical initiation system was found more suitable than the UV initiation system for antibacterial activity. Hydrogels showing the highest antibacterial activity on Staphylococcus aureus and Escherichia coli have medium or distributed pore size and interconnected pores. Hydrogels prepared with PEGM (M_n: 2000 g/mol) were proposed for antibacterial wound dressing and soft tissue regeneration applications owing to their antibacterial activity and elastic modulus. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42707.     

Mechanical reinforcement of hydrogels by nanofiber network undergoing biaxial deformation

Hydrogels can encapsulate large quantities of water within a three‐dimensional crosslinked polymer network. Polyvinyl alcohol (PVA) hydrogels have been widely used in tissue engineering, wound dressing, and drug delivery. However, the inferior mechanical properties of PVA hydrogels limit their utility in load‐bearing applications. To alleviate this deficiency, we used a hybrid electrospinning/solution casting continuous process to reinforce PVA hydrogels using polyurethane nanofibers. In this process, the nanofibers were electrospun into the wet solution cast film prior to solidification. The reinforcement of PVA hydrogels at a series of extent of water swelling was determined using a custom built bubble biaxial stretching device. The results showed that nanofibers have substantial enhancement effect on mechanical properties particularly in thin hydrogel films at high water concentrations. Reduction of nanofiber diameter was also found to increase this reinforcement due to increased interfacial area between nanofibers and hydrogels. POLYM. COMPOS., 37:709–717, 2016. © 2014 Society of Plastics Engineers     

Biodegradable polymers exhibiting temperature-responsive sol–gel transition as injectable biomedical materials

Injectable biodegradable copolymer hydrogels, which exhibit temperature-responsive sol-to-gel transition, have recently drawn much attention as promising biomedical materials such as drug delivery, cell implantation, and tissue engineering. These injectable hydrogels can be implanted in the human body with minimal surgical invasion. Temperature-responsive gelling copolymers usually possess block- and/or branched architectures and amphiphilicity with a delicate hydrophobic/hydrophilic balance. Poly(ethylene glycol) (PEG) has typically been used as hydrophilic segments due to its biocompatibility and temperature-dependent dehydration nature. Aliphatic polyesters such as polylactide, poly(lactide-co-glycolide), poly(ε-caprolactone), and their modified copolymers have been used as hydrophobic segments based on their biodegradability and biocompatibility. Copolymers of PEG with other hydrophobic polymers such as polypeptides, polydepsipeptides have also been recently reported as injectable hydrogels. In this review, brief history and recent advances in injectable biodegradable polymer hydrogels are summarized especially focusing on the relationship between polymer architecture and their gelation properties. Moreover, the applications of these injectable polymer gels for biomedical use such as drug delivery and tissue engineering are also described.     

Hydrogels with Reversible Crosslinks for Improved Localised Stem Cell Retention: A Review

Successful stem cell applications could have a significant impact on the medical field, where many lives are at stake. However, the translation of stem cells to the clinic could be improved by overcoming challenges in stem cell transplantation and in vivo retention at the site of tissue damage. This review aims to showcase the most recent insights into developing hydrogels that can deliver, retain, and accommodate stem cells for tissue repair. Hydrogels can be used for tissue engineering, as their flexibility and water content makes them excellent substitutes for the native extracellular matrix. Moreover, the mechanical properties of hydrogels are highly tuneable, and recognition moieties to control cell behaviour and fate can quickly be introduced. This review covers the parameters necessary for the physicochemical design of adaptable hydrogels, the variety of (bio)materials that can be used in such hydrogels, their application in stem cell delivery and some recently developed chemistries for reversible crosslinking. Implementing physical and dynamic covalent chemistry has resulted in adaptable hydrogels that can mimic the dynamic nature of the extracellular matrix.     

Thiol–norbornene photoclick hydrogels for tissue engineering applications

Thiol–norbornene (thiol–ene) photoclick hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are crosslinked through light‐mediated orthogonal reactions between multifunctional norbornene‐modified macromers [e.g., poly(ethylene glycol) (PEG), hyaluronic acid, gelatin] and sulfhydryl‐containing linkers (e.g., dithiothreitol, PEG–dithiol, biscysteine peptides) with a low concentration of photoinitiator. The gelation of thiol–norbornene hydrogels can be initiated by long‐wave UV light or visible light without an additional coinitiator or comonomer. The crosslinking and degradation behaviors of thiol–norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned because of the orthogonal reactivity between norbornene and the thiol moieties. Uniquely, the crosslinking of step‐growth thiol–norbornene hydrogels is not oxygen‐inhibited; therefore, gelation is much faster and highly cytocompatible compared with chain‐growth polymerized hydrogels with similar gelation conditions. These hydrogels have been prepared as tunable substrates for two‐dimensional cell cultures as microgels and bulk gels for affinity‐based or protease‐sensitive drug delivery, and as scaffolds for three‐dimensional cell encapsulation. Reports from different laboratories have demonstrated the broad utility of thiol–norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas‐related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, and cancer cell biology. This article provides an up‐to‐date overview on thiol–norbornene hydrogel crosslinking and degradation mechanisms, tunable material properties, and the use of thiol–norbornene hydrogels in drug‐delivery and tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41563.     

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.     

Formation of silk fibroin hydrogel and evaluation of its drug release profile

Silk hydrogels are interesting materials to be used as matrix in controlled drug delivery devices. However, methods to accelerate fibroin gelation and allow the drug incorporation during the hydrogel preparation are needed in literature. In this article we report the preparation of silk fibroin hydrogels with addition of several contents of ethanol, used to accelerate fibroin gelation kinetics, and we also evaluate the potential of these hydrogels to be used as matrices for drug delivery. Chemical and conformational properties did not change despite the amount of ethanol incorporated in the hydrogel. Hydrogels containing diclofenac sodium dissolved in ethanol showed a faster initial release of the drug than hydrogels with the drug dissolved in water but equilibrium was reached later. This indicates a more sustained drug delivery from hydrogels in which the model drug was dissolved in ethanol. Fibroin hydrogels confirm their promising use as biopolymeric matrices for controlled drug release. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41802.     

Synthesis of dual physical self-healing starch-based hydrogels for repairing tissue defects

Hydrogels have the potential to simulate and permeate body tissues. They can be used in many biomedical applications, such as drug delivery, wound dressings, contact lenses, synthetic implants, biosensors, and tissue engineering. Despite recent significant advances in hydrogel fabrication, with the introduction of double network hydrogels, with ionic or hydrogen bonds, there is still the challenge of achieving optimal mechanical properties with appropriate self-healing ability. To solve the above problem, in this study, a new type of starch/chitosan/PVA/borax hydrogel was synthesized by adopting the one-pot method. The effect of concentration and ratio of raw materials on the final properties of hydrogels, such as the degree of hydrophilicity, morphology, degradation, mechanical strength, and drug release rate, was investigated. The properties of hydrogels were examined by scanning electron microscopy, thermogravimetric analysis, Fourier-transform infrared spectroscopy, X-ray diffractometry, and contact angle, which confirmed the composite synthesis and uniform distribution of HNT and curcumin. In addition, the composite hydrogel showed excellent mechanical properties. Drug release studies confirmed that the drug is slowly released from the nanocomposite hydrogels. The results showed that starch-based nanocomposite hydrogels could provide appropriate repairing potential for defects exposed to changeable parameters.