Proteolytically Degradable Photo‐Polymerized Hydrogels Made From PEG–Fibrinogen Adducts

We develop a biomaterial based on protein–polymer conjugates where poly(ethylene glycol) (PEG) polymer chains are covalently linked to multiple thiols on denatured fibrinogen. We hypothesize that conjugation of large diacrylate‐functionalized linear PEG chains to fibrinogen could govern the molecular architecture of the polymer network via a unique protein–polymer interaction. The hypothesis is explored using carefully designed shear rheometry and swelling experiments of the hydrogels and their precursor PEG/fibrinogen conjugate solutions. The physical properties of non‐cross‐linked and UV cross‐linked PEGylated fibrinogen having PEG molecular weights ranging from 10 to 20 kDa are specifically investigated. Attaching multiple hydrophilic, functionalized PEG chains to the denatured fibrinogen solubilizes the denatured protein and enables a rapid free‐radical polymerization cross‐linking reaction in the hydrogel precursor solution. As expected, the conjugated protein‐polymer macromolecular complexes act to mediate the interactions between radicals and unsaturated bonds during the free‐radical polymerization reaction, when compared to control PEG hydrogels. Accordingly, the cross‐linking kinetics and stiffness of the cross‐linked hydrogel are highly influenced by the protein–polymer conjugate architecture and molecular entanglements arising from hydrophobic/hydrophilic interactions and steric hindrances. The proteolytic degradation products of the protein–polymer conjugates proves to be were different from those of the non‐conjugated denatured protein degradation products, indicating that steric hindrances may alter the proteolytic susceptibility of the PEG–protein adduct. A more complete understanding of the molecular complexities associated with this type of protein‐polymer conjugation can help to identify the full potential of a biomaterial that combines the advantages of synthetic polymers and bioactive proteins.     

Topological Adhesion of Wet Materials

Achieving strong adhesion between wet materials (i.e., tissues and hydrogels) is challenging. Existing adhesives are weak, toxic, incompatible with wet and soft surfaces, or restricted to specific functional groups from the wet materials. The approach reported here uses biocompatible polymer chains to achieve strong adhesion and retain softness, but requires no functional groups from the wet materials. In response to a trigger, the polymer chains form a network, in topological entanglement with the two polymer networks of the wet materials, stitching them together like a suture at the molecular scale. To illustrate topological adhesion, pH is used as a trigger. The stitching polymers are soluble in water in one pH range but form a polymer network in another pH range. Several stitching polymers are selected to create strong adhesion between hydrogels in full range of pH, as well as between hydrogels and various porcine tissues (liver, heart, artery, skin, and stomach). The adhesion energy above 1000 J m^?2 is achieved when the stitching polymer network elicits the hysteresis in the wet materials. The molecular suture can be designed to be permanent, transient, or removable on‐demand. The topological adhesion may open many opportunities in complex and diverse environments.     

Biocompatible zwitterionic copolymer networks with controllable swelling and mechanical characteristics of their hydrogels

The equilibrium swelling ratio in both water and physiological solution of the biocompatible copolymer networks of 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate (DMAPS) and N-vinyl-2-pyrrolidone (NVP) is determined as a function of copolymer composition. It is established that equilibrium swelling ratio of the polymer networks in physiological solution increase with raise of zwitterionic monomer unit fraction. A sharp decrease of this ratio in water with increase of zwitterionic monomer unit fraction is related to the formation of thermolabile physical junctions produced by dipole–dipole interactions between the zwitterionic side groups. The same fact affects considerably the storage and loss moduli of the copolymer hydrogels as well as the morphology of the dried networks. Scanning electron microscopy images provided evidence of the occurrence of a lamellar structure forming the morphology of the polymers. This was corroborated by differential scanning calorimetry experiments. In this way a possibility for effective control on swelling ratio in different solutions and the mechanical properties of these novel biocompatible networks are established.     

Hydrophobic Hydrogels with Fruit‐Like Structure and Functions

Normally, a polymer network swells in a good solvent to form a gel but the gel shrinks in a poor solvent. Here, an abnormal phenomenon is reported: some hydrophobic gels significantly swell in water, reaching water content as high as 99.6 wt%. Such abnormal swelling behaviors in the nonsolvent water are observed universally for various hydrophobic organogels containing omniphilic organic solvents that have a higher affinity to water than to the hydrophobic polymers. The formation of a semipermeable skin layer due to rapid phase separation, and the asymmetric diffusion of water molecules into the gel driven by the high osmotic pressure of the organic solvent–water mixing, are found to be the reasons. As a result, the hydrophobic hydrogels have a fruit‐like structure, consisting of hydrophobic skin and water‐trapped micropores, to display various unique properties, such as significantly enhanced strength, surface hydrophobicity, and antidrying, despite their extremely high water content. Furthermore, the hydrophobic hydrogels exhibit selective water absorption from concentrated saline solutions and rapid water release at a small pressure like squeezing juices from fruits. These novel functions of hydrophobic hydrogels will find promising applications, e.g., as materials that can automatically take the fresh water from seawater.     

Biofriendly,Stretchable, and Reusable Hydrogel Electronics as Wearable Force Sensors

The ever‐growing overlap between stretchable electronic devices and wearable healthcare applications is igniting the discovery of novel biocompatible and skin‐like materials for human‐friendly stretchable electronics fabrication. Amongst all potential candidates, hydrogels with excellent biocompatibility and mechanical features close to human tissues are constituting a promising troop for realizing healthcare‐oriented electronic functionalities. In this work, based on biocompatible and stretchable hydrogels, a simple paradigm to prototype stretchable electronics with an embedded three‐dimensional (3D) helical conductive layout is proposed. Thanks to the 3D helical structure, the hydrogel electronics present satisfactory mechanical and electrical robustness under stretch. In addition, reusability of stretchable electronics is realized with the proposed scenario benefiting from the swelling property of hydrogel. Although losing water would induce structure shrinkage of the hydrogel network and further undermine the function of hydrogel in various applications, the worn‐out hydrogel electronics can be reused by simply casting it in water. Through such a rehydration procedure, the dehydrated hydrogel can absorb water from the surrounding and then the hydrogel electronics can achieve resilience in mechanical stretchability and electronic functionality. Also, the ability to reflect pressure and strain changes has revealed the hydrogel electronics to be promising for advanced wearable sensing applications.     

Conducting polymer-hydrogels for medical electrode applications

Abstract

Conducting polymers hold significant promise as electrode coatings; however, they are characterized by inherently poor mechanical properties. Blending or producing layered conducting polymers with other polymer forms, such as hydrogels, has been proposed as an approach to improving these properties. There are many challenges to producing hybrid polymers incorporating conducting polymers and hydrogels, including the fabrication of structures based on two such dissimilar materials and evaluation of the properties of the resulting structures. Although both fabrication and evaluation of structure–property relationships remain challenges, materials comprised of conducting polymers and hydrogels are promising for the next generation of bioactive electrode coatings.     

Charakterisierung von Plasmapolymeren mittels Thermolumineszenzmessungen

Characterization of Plasmapolymers by Thermoluminescence Thin plasma polymer films were deposited using the pulsed plasma (pp) mode. These plasma polymers should possess a more chemically regular structure because of the lower monomer fragmentation during the short plasma pulses and the chemical chain propagation during the plasma‐less periods than those produced by the conventional continuous‐wave (cw) mode. In addition to the use of the classic thin film characterization method XPS the method of thermoluminescence was applied to characterize defects and structural specifics in the polymer films produced by pp or cw‐plasma mode. The thermoluminescence method was applied to functional groups‐carrying plasma polymer layers, which are used in medical technology for forming biocompatible and bioactive coatings or in metal‐polymer composites as adhesion‐promoting interlayers.     

Dendritic Polyglycerols for Biomedical Applications

The application of nanotechnology in medicine and pharmaceuticals is a rapidly advancing field that is quickly gaining acceptance and recognition as an independent area of research called “nanomedicine”. Urgent needs in this field, however, are biocompatible and bioactive materials for antifouling surfaces and nanoparticles for drug delivery. Therefore, extensive attention has been given to the design and development of new macromolecular structures. Among the various polymeric architectures, dendritic (“treelike”) polymers have experienced an exponential development due to their highly branched, multifunctional, and well‐defined structures. This Review describes the diverse syntheses and biomedical applications of dendritic polyglycerols (PGs). These polymers exhibit good chemical stability and inertness under biological conditions and are highly biocompatible. Oligoglycerols and their fatty acid esters are FDA‐approved and are already being used in a variety of consumer applications, e.g., cosmetics and toiletries, food industries, cleaning and softening agents, pharmaceuticals, polymers and polymer additives, printing photographing materials, and electronics. Herein, we present the current status of dendritic PGs as functional dendritic architectures with particular focus on their application in nanomedicine, in drug, dye, and gene delivery, as well as in regenerative medicine in the form of non‐fouling surfaces and matrix materials.     

Novel transducers for nano-optical biosensor chips based on biological and synthetic polymers with analyte-dependent swelling/shrinking behavior

Analyte-dependent swelling/shrinking properties of ultrathin polymer layers are an appropriate means for the detection of various analytes. Optical metal nanoclusters can be used to determine the change of the layer's thickness, which is shown by a change in the color of the chip. By using different cross-linking agents and different polymers (biological or artificial as well) it was possible to design various sensitive layers showing different swelling/shrinking behaviors. Sensitivity on various analytes could be observed, since the different types of polymers employed differed in structure, functional groups, or biorecognitive properties.     

Hydrogels of Thermoreversible Comb‐Polymers Exhibit Increased Resistance for Dissolution

The N‐isopropylacrylamide (NiPAM) polymers exhibit thermoreversible properties in aqueous solutions. The resiliency of NiPAM hydrogels is believed to influence the outcome when the polymers are utilized in biomedical applications. To determine the influence of polymer architecture on hydrogel resiliency, polymers of NiPAM, methyl methacrylate (MMA) and acrylic acid were synthesized as random polymers and as comb polymers, where MMA was incorporated as side‐chains. Random polymers exhibited a Lower Critical Solution Temperature (LCST) that decreased in proportion to MMA content in polymers. The LCST of comb polymers was not dependent on MMA content or the length of MMA side‐chain (between 3.0 and 10.1 kD). Whereas low molecular weight (～100 kD) random polymers did not form intact gels, comb‐polymers of equivalent molecular weight were capable of forming intact gels. Gel resiliency, as determined by propensity of hydrogels to dissolve upon cooling, was improved when the molecular weight of comb‐polymers was increased but the length of the MMA side‐branch did not influence the gel resiliency. We conclude that hydrogel dissolution was dependent on polymer architecture as well as the polymer molecular weight.     

Funktionelle Beschichtungen auf Basis anorganischer Nanosole

Functional coatings on basis of inorganic nanosols The controlled hydrolysis of silicon or metal alkoxides produces nanoparticulate oxide sols which condense to thin transparent gel films on any substrates after coating and drying (so‐called “sol‐gel process”). The co‐hydrolysis and co‐condensation of different alkoxides (chemical modification) as well as the embedding of different additives (physical modification) offers almost unlimited possibilities to vary the properties of nanosols and, therefore, also of the resulting coatings, and to adapt them to the purpose intended. By coating of flexible substrates like textiles, papers or polymer foils it is possible to combine the material protecting functions of the inorganic oxide layer with new functional qualities, e. g. modification of surface energy and charge, alteration of the optical properties, realization of biocompatible and bioactive properties.     

Preparation and characterization of novel biocompatible cryogels of poly (vinyl alcohol) and egg-albumin and their water sorption study

Polyvinyl alcohol (PVA) and egg albumin are water-soluble, biocompatible and biodegradable polymers and have been widely employed in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of poly (vinyl alcohol) and egg albumin were prepared by cyclic freezing/thawing processes of aqueous solutions containing PVA and egg albumin. The FTIR analysis of prepared cryogels indicated that egg albumin was successfully introduced into the formed hydrogel possibly via hydrogen bonds among hydroxyl groups, amide groups and amino groups present in PVA and egg albumin. The gels were also characterized thermally and morphologically by DSC and SEM-techniques, respectively. The prepared so called ‘cryogels’ were evaluated for their water uptake potential and influence of various factors such as chemical architecture of the spongy hydrogels, pH and temperature of the swelling bath were investigated on the degree of water sorption by the cryogels. The effect of salt solution and various simulated biological fluids on the swelling of cryogel was also studied. The in vitro biocompatibility of the prepared cryogel was also judged by methods such as protein (BSA) adsorption, blood clot formation and percentage hemolysis measurements.     

Fabrication of Novel Membranes for Biomedical Applications via Halidation of Poly(Methacrylic Acid‐co‐Methyl Methacrylate) and Crosslinking of Complementary Groups by PEG

Fabrication of novel, biocompatible and stimuli‐responsive membranes based on the crosslinking of poly(methacrylic acid‐co‐methyl methacrylate) using polyethylene glycol as a crosslinking agent is accomplished in a two‐stage procedure. Membranes are fabricated by casting and curing of the reactive precursors in different reaction compositions and durations according to a three‐level factorial design‐of‐experiments. The resulting membranes were thoroughly characterized using SEM, FTIR spectroscopy, thermal analysis and swelling experiments. The thermal properties were improved and swelling behavior of the hydrogels assures its stimuli‐responsive nature. MTT‐assay and cytotoxicity evaluations of the fabricated membranes elucidate acceptable biocompatibility profiles.     

Chitosan-based hydrogels: Synthesis and characterization

Chitosan (CHI) is a polysaccharide of beta-1,4-linked 2-amino-2-deoxy-D-glucopyranose derived by N-deacetylation of chitin in aqueous alkaline medium. The shells of crustaceans such as crabs, shrimp, and lobster are the current source of chitosan. It is known to be non-toxic, odourless, biocompatible in animal tissues and enzymatically biodegradable. For these reasons much research interest has been paid to its biomedical, ecological, and industrial applications over the past decade. However, its rigid crystalline structure, poor solubility in organic solvents and poor processability have limited its use. To broadening its range of applications, a growth research effort has been devoted to explore ways of modifying Chitosan. Here it has been reported on the synthesis of new hydrogels, obtained by self-curing chitosan with acrylic acid (AA) and methyl acrylate (MA). The hydrogels were characterized by FTIR, swelling and rheological analysis. The results of this study showed that the swelling and mechanical properties of chitosan are highly improved by the presence of poly acrylate. The swelling degree of these materials does not depend upon the ratio MA/AA. It is possible to improve and modulate the mechanical properties of the hydrogels by changing the relative MA/AA ratio.     

疏水改性聚N-异丙基丙烯酰胺的性能及对溶液组成的依赖性

采用自由基胶束水溶液聚合方法制备了疏水改性聚N-异丙基丙烯酰胺水凝胶(P(NIPA-co-MA／EA／BA／DA)),研究了该类水凝胶和PNIPA水凝胶在去离子水及NaCl、Na2SO4、乙醇水溶液中的溶胀行为及与温度的关系。结果表明,聚合物水凝胶在水溶液中的行为与凝胶化学结构、温度、水溶液中的溶质的种类和含量有关。     

Development of in situ-forming hydrogels for hemorrhage control

We report the preparation of in situ-forming hydrogels, composed of oxidized dextran (Odex) and amine-containing polymers, for their potential use as a wound dressing to promote blood clotting. Dextran was oxidized by sodium periodate to introduce aldehyde groups to form hydrogels, upon mixing in solution with different polymers containing primary amine groups, including polyallylamine (PAA), oligochitosan and glycol chitosan. A series of experiments were conducted to identify the optimum gelation condition for the Odex-PAA system. The polymer concentration appeared to have a major effect on gelation time and the polymer weight ratio affected the resulting gel content and swelling. Other influencing factors included pH of the buffer used to dissolve each polymer, PAA molecular weight, and the type of individual material. The latter also contributed significantly to gel content and swelling. Thromboelastography was used to examine the effects of the in situ gelation on blood coagulation in vitro, where the Odex-PAA combination was found to be most pro-hemostatic, as indicated by a decrease in clotting time and an increase in clot strength. The results of this study demonstrated that in situ-forming hydrogels could promote clotting in vitro; however, further studies are required to determine if the same hydrogel formulations are effective in controlling hemorrhage in vivo.     

Creating Stiff,Tough, and Functional Hydrogel Composites with Low‐Melting‐Point Alloys

Reinforcing hydrogels with a rigid scaffold is a promising method to greatly expand the mechanical and physical properties of hydrogels. One of the challenges of creating hydrogel composites is the significant stress that occurs due to swelling mismatch between the water‐swollen hydrogel matrix and the rigid skeleton in aqueous media. This stress can cause physical deformation (wrinkling, buckling, or fracture), preventing the fabrication of robust composites. Here, a simple yet versatile method is introduced to create “macroscale” hydrogel composites, by utilizing a rigid reinforcing phase that can relieve stress‐induced deformation. A low‐melting‐point alloy that can transform from a load‐bearing solid state to a free‐deformable liquid state at relatively low temperature is used as a reinforcing skeleton, which enables the release of any swelling mismatch, regardless of the matrix swelling degree in liquid media. This design can generally provide hydrogels with hybridized functions, including excellent mechanical properties, shape memory, and thermal healing, which are often difficult or impossible to achieve with single‐component hydrogel systems. Furthermore, this technique enables controlled electrochemical reactions and channel‐structure templating in hydrogel matrices. This work may play an important role in the future design of soft robots, wearable electronics, and biocompatible functional materials.     

Composite Microgels Created by Complexation between Polyvinyl Alcohol and Graphene Oxide in Compressed Double‐Emulsion Drops

Microgels, microparticles made of hydrogels, show fast diffusion kinetics and high reconfigurability while maintaining the advantages of hydrogels, being useful for various applications. Here, presented is a new microfluidic strategy for producing polymer‐graphene oxide (GO) composite microgels without chemical cues or a temperature swing for gelation. As a main component of microgels, polymers that are able to form hydrogen bonds, such as polyvinyl alcohol (PVA), are used. In the mixture of PVA and GO, GO is tethered by PVA through hydrogen bonding. When the mixture is rapidly concentrated in the core of double‐emulsion drops by osmotic‐pressure‐driven water pumping, PVA‐tethered GO sheets form a nematic phase with a planar alignment. In addition, the GO sheets are linked by additional hydrogen bonds, leading to a sol–gel transition. Therefore, the PVA–GO composite remains undissolved when it is directly exposed to water by oil‐shell rupture. These composite microgels can be also produced using poly(ethylene oxide) or poly(acrylic acid), instead of PVA. In addition, the microgels can be functionalized by incorporating other polymers in the presence of the hydrogel‐forming polymers. It is shown that the multicomponent microgels made from a mixture of polyacrylamide, PVA, and GO show an excellent adsorption capacity for impurities.     

Bio‐Interface of Conducting Polymer‐Based Materials for Neuroregeneration

Nerve system diseases like Parkinson's disease, Huntington's disease, Alzheimer's disease, etc. seriously affect thousands of patients' lives every year, making them suffer from pains and inconvenience. Recently, bio‐interfaces between neural cells/tissues and polymer based biomaterials attracted worldwide attention due to the ability of polymer based biomaterials to serve as nerve conduits, drug carriers and neurites guidance platform in neuroregeneration. The role that bio‐interface played and the way it interacted with neural tissues and cells have been thoroughly investigated by the researchers. In this paper we mainly focus on reviewing the bio‐interface between nerve tissues/cells and advanced functional biocompatible polymers, such as conducting polymers and advanced carbon composite materials. These advanced polymers can provide combined interfacial stimulations including interfacial external neurotrophic factors (NTFs) delivery, electrical stimulation, surface guidance and molecules decoration to lesion cells and tissues to promote neuroregeneration in vitro and in vivo, and have contributed greatly to nerve diseases therapy. At the end of this review, the criteria of polymer based biomaterials utilized in neuroregeneration are summarized and the perspectives for future development of bio‐interfaces are also discussed.     

Microstructured,Functional PVA Hydrogels through Bioconjugation with Oligopeptides under Physiological Conditions

In this work, bioconjugation techniques are developed to achieve peptide functionalization of poly(vinyl alcohol), PVA, as both a polymer in solution and within microstructured physical hydrogels, in both cases under physiological conditions. PVA is unique in that it is one of very few polymers with excellent biocompatibility and safety and has FDA approval for clinical uses in humans. However, decades of development have documented only scant opportunities in bioconjugation with PVA. As such, materials derived thereof fail to answer the call for functional biomaterials for advanced cell culture and tissue engineering applications. To address these limitations, PVA is synthesized with terminal thiol groups and conjugated with thiolated peptides using PVA in solution. Further, microstructured, surface‐adhered PVA physical hydrogels are assembled, the available conjugation sites within the hydrogels are quantified, and quantitative kinetic data are collected on peptide conjugation to the hydrogels. The success of bioconjugation in the gel phase is quantified through the use of a cell‐adhesive peptide and visualization of cell adhesion on PVA hydrogels as cell culture substrates. Taken together, the presented data establish a novel paradigm in bioconjugation and functionalization of PVA physical hydrogels. Coupled with an excellent safety profile of PVA, these results deliver a superior biomaterial for diverse biomedical applications.