Synthesis and preparation of biodegradable and visible light crosslinkable unsaturated fumarate‐based networks for biomedical applications

Biodegradable polymers have currently attracted high interest as ideal carriers in drug delivery and tissue engineering applications. In situ forming devices based on these materials will synergistically provide the advantages of the customary prefabricated devices as well as ease of administration. To acheive these objectives, optically transparent and biodegradable macromers based on poly(ethylene glycol) and fumaric acid copolymers were synthesized using propylene oxide as a different proton scavenger to enhance in situ photocrosslinking capability. The macromers in different compositions were then photocured for 300 sec in the presence of a visible light initiator/accelerator couple and also a reactive diluent. Characterization of the macromers and the resulting networks were performed using different spectroscopic, chromatographic, physical, and thermal analysis techniques. The resulted shrinkage strain of the macromers upon photocuring was studied using the bounded disk technique, and initial shrinkage strain rates were obtained by numerical differentiation. Our results suggest that the compositions based on these unsaturated aliphatic polyesters are potentially useful to develop injectable, in situ photocrosslinkable carriers for drug and cell delivery applications. Copyright © 2008 John Wiley & Sons, Ltd.     

N‐vinylcaprolactam‐based microgels for biomedical applications

Three types of poly(N‐vinylcaprolactam)‐based temperature‐sensitive microgel particles were synthesized by emulsion polymerization. The uptake of a model drug (calcein) into the particles was analyzed in terms of the amount of calcein absorbed and equilibrium–swelling degree. By incubating the microgels with primary neuronal cell cultures of embrionary rats, cell viability and biocompatibility tests were carried out. The results show that the driving force for the model drug to penetrate into the microgel particles is H‐bonding associations. On the other hand, cell death was microgel concentration and incubation period dependent. Microgels can be stored in a dried state and resuspended in water when necessary without changing their swelling–deswelling ability. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1173–1181, 2010     

Synthesis of thermal‐stable and photo‐crosslinkable polyfluorenes for the applications of polymer light‐emitting diodes

Three polyfluorene derivatives which have oxetane‐containing phenyl group at C‐9 position were synthesized via the palladium‐catalyzed Suzuki‐coupling reaction. The synthesized polymers PFB, PFG, and PFR emit blue, green, and red light, respectively. A double‐layer device with the configuration of ITO/PEDOT/polymer/Ca/Al using PFB as the active layer showed a threshold voltage of 5 V, a maximum brightness of 2030 cd/m², and a maximum current efficiency of 0.35 cd/A. Using PFG as the active layer, the device exhibited a threshold voltage of 6 V, a maximum brightness of 6447 cd/m², and a maximum current efficiency of 1.27 cd/A. Using PFR as the active layer, the device showed a threshold voltage of 4 V, a maximum brightness of 2135 cd/m², and a maximum current efficiency of 0.16 cd/A. Better electroluminescent performance was also found based on different design of device structures. Due to photo‐crosslinking property of oxetane groups, the UV‐exposed thin films are insoluble in common organic solvents. A device comprised of blue, green, and red‐emissive pixels was successfully fabricated by spin‐coating and photo‐lithographic processes. In addition, a white light‐emitting device with CIE coordinate of (0.34, 0.33) was achieved by blending PFR into a host material PFB as the active layer. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 516–524, 2010     

Droplet‐based microfluidics systems in biomedical applications

Microfluidics has made a very impressive progress in the past decades due to its unique and instinctive advantages. Droplet‐based microfluidic systems show excellent compatibility with many chemical and biological reagents and are capable of performing variety of operations that can implement microreactor, complex multiple core–shell structure, and many applications in biomedical research such as drug encapsulation, targeted drug delivery systems, and multifunctionalization on carriers. Droplet‐based systems have been directly used to synthesize particles and encapsulate many biological entities for biomedicine applications due to their powerful encapsulation capability and facile versatility. In this paper, we review its origin, deviation, and evolution to draw a clear future, especially for droplet‐based biomedical applications. This paper will focus on droplet generation, variations and complication as starter, and logistically lead to the numerous typical applications in biomedical research. Finally, we will summarize both its challenge and future prospects relevant to its droplet‐based biomedical applications.     

Graphene‐polymer nanocomposites for biomedical applications

Despite the significant efforts in the synthesis of new polymers, the mechanical properties of polymer matrices can be considered modest in most cases, which limits their application in demanding areas. The isolation of graphene and evaluation of its outstanding properties, such as high thermal conductivity, superior mechanical properties, and high electronic transport, have attracted academic and industrial interest, and opened good perspectives for the integration of graphene as a filler in polymer matrices to form advanced multifunctional composites. Graphene‐based nanomaterials have prompted the development of flexible nanocomposites for emerging applications that require superior mechanical, thermal, electrical, optical, and chemical performance. These multifunctional nanocomposites may be tailored to synergistically combine the characteristics of both components if proper structural and interfacial organization is achieved. The investigations carried out in this aim have combined graphene with different polymers, leading to a variety of graphene‐based nanocomposites. The extensive research on graphene and its functionalization, as well as polymer graphene composites, aiming at applications in the biomedical field, are reviewed in this paper. An overview of the polymer matrices adequate for the biomedical area and the production techniques of graphene composites is presented. Finally, the applications of such nanocomposites in the biomedical field, particularly in drug delivery, wound healing, and biosensing, are discussed.     

Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications

Injectable hydrogels with biodegradability have in situ formability which in vitro/in vivo allows an effective and homogeneous encapsulation of drugs/cells, and convenient in vivo surgical operation in a minimally invasive way, causing smaller scar size and less pain for patients. Therefore, they have found a variety of biomedical applications, such as drug delivery, cell encapsulation, and tissue engineering. This critical review systematically summarizes the recent progresses on biodegradable and injectable hydrogels fabricated from natural polymers (chitosan, hyaluronic acid, alginates, gelatin, heparin, chondroitin sulfate, etc.) and biodegradable synthetic polymers (polypeptides, polyesters, polyphosphazenes, etc.). The review includes the novel naturally based hydrogels with high potential for biomedical applications developed in the past five years which integrate the excellent biocompatibility of natural polymers/synthetic polypeptides with structural controllability via chemical modification. The gelation and biodegradation which are two key factors to affect the cell fate or drug delivery are highlighted. A brief outlook on the future of injectable and biodegradable hydrogels is also presented (326 references).     

Synthesis of zirconia‐incorporated titania layer by microarc oxidation for biomedical applications

The structural features, biocompatibility, and mechanical performance of a titania (TiO₂) layer with incorporated zirconia (ZrO₂) formed by microarc oxidation on commercially pure titanium have been examined in the present study. In comparison to the ZrO₂‐free TiO₂ layer, the ZrO₂‐incorporated oxide layer was dense and contained ZrTiO₄ as a new oxide as well as ZrO₂ particles. Associated changes in the microstructure enhanced the mechanical durability of TiO₂ layer. Owing to the incorporation of identical biocompatible compounds and almost similar surface roughness, no remarkable difference in bioactivities of the ZrO₂‐free and ZrO₂‐incorporated oxide layers was detected after simulated body fluid tests. Copyright © 2015 John Wiley & Sons, Ltd.     

Molecular design of biologically active biodegradable polymers for biomedical applications

The objective of this research is to synthesize synthetic biodegradable polymers that would have biological functions similar to nitric oxide. Polyglycolide (PGA) was the synthetic biodegradable polymer and 4-amino-2,2,6,6-tetramethylpiperidine-1-oxy (Tempamine) was chosen as the source of nitroxyl radicals. Tempamine nitroxyl radicals were chemically incorporated into the carboxylic acid chain ends of PGA macromolecules via amide linkage. The kinetics of in vitro hydrolytic release of Tempamine nitroxyl radicals from the host PGA in buffered media at 37 °C was studied. Tempamine nitroxyl radicals were released into the media via cleavage of either ester linkages in the PGA segments or/and the amide linkage between Tempamine and the PGA segments. The duration of hydrolysis would determine the type of degradation products that were different in the segmental length of the PGA component. A preliminary in vitro cell culture study of this new generation of biologically active biodegradable polymers indicated that it was able to retard the proliferation of smooth muscle cells as pure nitric oxide does.     

Synthesis and in vitro degradation of poly(N‐vinyl‐2‐pyrrolidone)‐based graft copolymers for biomedical applications

This work is devoted to the design of a novel family of hydrosoluble biomaterials: poly(N‐vinyl‐2‐pyrrolidone) (PVP)‐based graft copolymers. A synthesis route has been elaborated in which ω‐functionalized PVP is prepared via chain‐transfer radical polymerization, end‐group modified, and subsequently grafted onto a polyhydroxylated backbone, typically dextran or poly(vinyl alcohol). The resulting graft copolymer biomaterials are designed for use in various biomedical applications, particularly as materials with a stronger potential for plasma expansion than already existing products have. The graft copolymers are potentially degradable because the PVP grafts are connected to the polyol backbone via a hydrolytically labile carbonate or ester linkage. The degradation of the graft copolymers was performed in vitro over a period of 6 weeks. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3652–3661, 2002     

Hydrophilic stimuli‐responsive particles for biomedical applications

Hydrophilic and stimuli‐responsive submicronic latex particles based on polyalkyl(meth)acrylamide can be prepared owing to simple radical‐initiated polymerizations in heterogeneous media using a water‐soluble initiator and a crosslinker (methylenebisacrylamide). The paper aims at reviewing the synthesis and properties of functionalized polystyrene‐polyN‐isoprpylacrylamide core‐shell particles or polyN‐isopropylmethacrylamide microgel particles. Particle size of analysis showed that a short nucleation period afforded the synthesis of highly monodispersed latexes. The dramatic change of the colloidal properties (particle size, electrophoretic mobility) was found to reflect the thermal sensitivity of such particles. The hydrophilic nature of the particles below the volume phase transition temperature was found to drastically reduce the physical adsorption of proteins. Some examples of biomedical applications of these stimuli‐responsive particles are briefly reported.     

Synthesis and characterization of thermally crosslinkable hole‐transporting polymers for PLEDs

Two new thermally crosslinkable hole‐transporting polymers, X‐PTPA and X‐PCz, were synthesized via Yamamoto coupling reactions. The number‐averaged molecular weights (M_n) of X‐PTPA and X‐PCz were found to be 45,000 and 48,000, respectively, and therewith, polydispersity indices were of 1.8 and 1.7, respectively. Thermally crosslinked X‐PTPA and X‐PCz exhibit excellent solvent resistance and stable optoelectronic properties. The UV–visible maximum absorption peaks of X‐PTPA and X‐PCz in the thin film state are at 389 and 322 nm, respectively. The HOMO levels of X‐PTPA and X‐PCz are estimated to be ?5.27 and ?5.39 eV, respectively. Multilayered devices (ITO/crosslinked X‐PTPA or X‐PCz/SY‐PPV/LiF/Al) were fabricated with SY (SuperYellow) as the emitting layer. The maximum efficiency of the multilayered device with a crosslinked X‐PTPA layer is approximately three times higher than that of the device without a crosslinked X‐PTPA layer and much higher than that of the crosslinked X‐PCz device. This result can be explained by the observations that crosslinked X‐PTPA produces increased electron accumulation within the emitter, SY, and also efficient exciton formation due to improved charge balance. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5111–5117     

Synthesis and aggregation behavior of chitooligosaccharide‐based biodegradable graft copolymers

A series of novel “jellyfish‐like” graft copolymers with chitooligosaccharide (COS) as shorter backbone and poly(ε‐caprolactone) as longer branches were synthesized using ring‐opening polymerization of ε‐caprolactone via a protection‐polymerization‐deprotection procedure with trimethylsilylchitooligosaccharide as intermediate and triethylaluminum as catalyst precursor. The obtained chitooligosaccharide‐graft‐poly(ε‐caprolactone) polymers possess amphiphilic structure with hydrophilic COS backbone and hydrophobic polycaprolactone branches. Because of this unique “jellyfish‐like” structure, these graft copolymers could self‐assemble to form various morphologies of aggregates in a mixture solution of water and tetrahydrofuran. The transmission electron microscopy studies revealed that the formed aggregates exhibited necklace‐like, flower‐like onion vesicle, and tubular morphologies. It is found that the hydrogen‐bonding formed by the hydroxyl and amino groups remained on the COS backbone played an important role during the aggregation of these graft copolymers, and their morphologies were changed with the varying length of poly (ε‐caprolactone) branches, the concentration of the graft copolymer, and the self‐assembly process. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4889–4904, 2008     

A visible light responsive azobenzene‐functionalized polymer: Synthesis,self‐assembly,and photoresponsive properties

A novel visible light responsive random copolymer consisting of hydrophobic azobenzene‐containing acrylate units and hydrophilic acrylic acid units has been prepared. The azobenzene molecule bearing methoxy groups at all four ortho positions is readily synthesized by one‐step conversion of diazotization. The as‐prepared polymer can self‐assemble into nanoparticles in water due to its amphiphilic nature. The tetra‐o‐methoxy‐substituted azobenzene‐functionalized polymer can exhibit the trans‐to‐cis photoswitching under the irradiation with green light of 520 nm and the cis‐to‐trans photoswitching under the irradiation with blue light of 420 nm in both solution and aggregate state. The morphologies of the self‐assembled nanoparticles are revealed by TEM and DLS. The controlled release of loaded molecules from the nanoparticles can be realized by adjusting pH value since the copolymer possesses pH responsive acrylic acid groups. The fluorescence of loaded Nile Red in the nanoparticles can be tuned upon the visible light irradiation. The reversible photoswitching of the azobenzene‐functionalized polymer under visible light may endow the polymer with wide applications without using ultraviolet light at all. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2768–2775     

Hydrophilic CO2‐based biodegradable polycarbonates: Synthesis and rapid thermo‐responsive behavior

Common CO₂‐based biodegradable polycarbonates like poly(propylene carbonate) or poly(cyclohexene carbonate) are generally hydrophobic, leading to slow biodegradation rate and poor cell adhesion, which limit their applications in the biomedical field. Here hydrophilic polycarbonates were prepared by one‐pot terpolymerization of CO₂, propylene oxide (PO), and 2‐((2‐(2‐(2‐methoxyethoxy)ethoxy)ethoxy)methyl)oxirane (ME₃MO) using binary Salen Co(III)‐Cl/PPNCl catalyst system. The resultant terpolymers showed one glass transition temperature (T_g), which decreased with the increase of ME₃MO units in the terpolymers (F_ME3MO). Water contact angles of the resultant terpolymers with F_ME3MO of 4.2?23.6% were 68?25°, while that of poly(propylene carbonate) was 90°, indicating that the terpolymers became hydrophlilic. Furthermore, the terpolymers with F_ME3MO more than 25.8% exhibited reversible and rapid thermo‐responsive property in water, and the lower critical solution temperature (LCST) was highly sensitive to F_ME3MO. In particular, aqueous solution of the terpolymer with F_ME3MO of 72.6% showed a LCST around 35.2 °C, close to body temperature, which was promising for biomedical applications, especially for in vivo applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2834–2840.     

Synthesis and properties of waterborne self‐crosslinkable sulfo‐urethane silanol dispersions

A novel type of crosslinkable waterborne polyurethane ionomer was prepared by the acetone process. Two new types of sulfonated diols compatible with this process were synthesized from dimethyl 5‐sodium sulfo isophthalate using a one‐ or two‐stage method. Isocyanate‐terminated polyurethane oligomers were prepared from the sulfonated diols with various combinations of diols and diisocyanates and subsequently reacted with amino silane derivatives. Stable, low‐volatile organic chemical, waterborne dispersions of the sulfo‐urethane silanol polymers spontaneously crosslink upon drying without extra additives or processing steps. Despite the lack of organic coalescing solvents, the dispersions have minimum film‐forming temperatures below 10 °C, regardless of glass‐transition temperature. Tensile strengths up to 6000 psi with elongations between 300 and 600% were obtained for the crosslinked films. The hard‐segment content of the films can be controlled to produce films with a Sward–Rocker hardness value up to 42. Through silane end‐group modification, the crosslinking density of the films can also be modified to produce polyurethanes with a wide range of physical properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3037–3045, 2002     

Synthesis of water soluble, biodegradable, and electroactive polysaccharide crosslinker with aldehyde and carboxylic groups for biomedical applications

We report the synthesis and characterization of a polysaccharide crosslinker of tetraaniline grafting oxidized sodium alginate with large aldehyde and carboxylic groups. We demonstrate that this copolymer has the following properties: it is water soluble under any pH, biodegradable, electroactive, and noncytotoxic; it can self-assemble into nanoparticles with large active functional groups on the outer surface; it can crosslink materials with amino and aminoderivative groups like gelatin to form hydrogels, and thus the electroactivity is readily introduced to the materials. This copolymer has potential applications in biomedical fields such as tissue engineering, drug delivery, and nerve probes where electroactivity is required.     

Agarose-polyaldehyde microsphere beads: Synthesis and biomedical applications

Polyaldehyde microspheres, polyglutaraldehyde (PGL), and polyacrolein (PA) were synthesized by polymerizing glutaraldehyde and acrolein in the presence of an appropriate surfactant. The microspheres with average diameter of 0.2 micron were used for the specific labeling of human red blood cells (RBC) and mouse lymphocytes. The "naked" microspheres were encapsulated with agarose and formed agarose-polyaldehyde microsphere beads in sizes ranging from 50 microns up to 1 cm. The encapsulated beads, with diameters ranging from 50 to 150 microns were used as insoluble adsorbents for affinity purification of antibodies. Beads with diameters varied from 150 to 250 microns were used for cell fractionation purposes (mouse B splenocytes from T splenocytes). Uniform beads of 1 mm diameter were designed for hemoperfusion purposes. As a model, the removal in vitro of anti-BSA from immunized goat whole blood was studied.     

Antifouling zwitterionic pSBMA‐MSN particles for biomedical applications

Mesoporous silica nanoparticles (MSNs) are one of the most promising nanocarriers in biomedicine. Nonetheless, surface modification has been pointed out as a condition necessary for drug delivery applications, where stability and biocompatibility are extremely important for the vehicle performance. Likewise, zwitterionic polymers are outstanding candidates in biological fields, where poly(sulfobetaine methacrylate) (pSBMA) has been widely studied. These polymers, known as antifouling materials, are able to render a surface capacity to avoid protein adhesion. In this work, a core‐shell nanocarrier was created, where pSBMA was covalently grafted by atom transfer radical polymerization (ATRP) onto a previously functionalized MSN surface. Brush morphologies with different chain lengths ( , between 6500 and 32 300) and graft densities (σ_pSBMA, between 0.15 and 0.51 molecules of pSBMA per nm² of MSN) were obtained. Protein adhesion resistance was evaluated with two proteins: fibronectin (FN) and bovine serum albumin (BSA). The best nanocarrier synthesized allowed a reduction of 96% of FN and 76% of BSA adhesion (compared with an adsorption of 100% assigned to the native material). Since the influence of the brush morphology is seldom studied or reported, this work aims to comprehend how the configuration of the polymer brushes affected their antifouling capacity, in order to use this pSBMA‐MSN product for biomedical applications, notably as a possible drug delivery nanocarrier. Future work will analyze the solution behavior of the zwitterionic brushes to evaluate variations of temperature and pH values as possible mechanisms of delivery.     

Synthesis and evaluation of new phosphonic acid‐functionalized acrylamides with potential biomedical applications

Phosphorus‐containing acidic monomers are able to interact with the inorganic phase of mineralized tissues such as enamel, dentin, and bone. From this perspective, three phosphonic acid‐containing acrylamide monomers with different lengths of alkyl chains were synthesized to be used for both self‐etching dental adhesives and mineralized hydrogel scaffolds. Monomers were synthesized by the reaction of α‐aminophosphonates (diethyl aminomethylphosphonate, diethyl 2‐aminobutan‐2‐ylphosphonate, and diethyl 2‐aminooctan‐2‐ylphosphonate) with acryloyl chloride followed by the hydrolysis of phosphonate groups by using trimethylsilyl bromide. The properties such as pH in the range of mild self‐etching adhesives, hydrolytic stability, high rate of copolymerizations with 2‐hydroxyethyl methacrylate (HEMA) and HEMA/glycerol dimethacrylate, giving high‐molecular‐weight polymers on thermal polymerization, and strong decalcification ability of hydroxyapatite make these monomers good candidates for self‐etching adhesives, although no appreciable effect of the number and size of the α‐substituents was observed. Hydrogel scaffolds containing phosphonic acid groups were fabricated, characterized, and mineralized. Altogether, the results suggest that these phosphonic acid‐containing monomers have suitable properties to be used in fabrication of biomaterials for both dental and bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2755–2767     

Synthesis and characterization of epoxy‐based semi‐interpenetrating polymer networks sulfonated polyimides proton‐exchange membranes for direct methanol fuel cell applications

Novel epoxy‐based semi‐interpenetrating polymer networks (semi‐IPNs) of aromatic polyimide, derived from 2,2‐benzidinedisulfonic acid (BDSA), were prepared through a thermal imidization reaction. Dynamic scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were utilized to verify the synchronization of the imidization of sulfonated poly(amic acid) (SPAA) and the crosslinking reactions of epoxy. The semi‐IPNs of epoxy/sulfonated polyimides (SPI‐EPX) exhibit excellent film‐forming characteristics and mechanical integrity at room temperature. Conductivities at 100 °C of 0.0243 S cm^?1 (SPI‐EP30) and 0.0141 S cm^?1 (SPI‐EP50) were obtained, which are similar to that of the Nafion 117 (0.0287 S cm^?1). The increase in the conductivity of SPI‐EP(30,40) with temperature is more rapid than that of Nafion 117. The SPI‐EPX exhibited lower methanol permeability than did Nafion117. The hydrolytic stability of the SPI‐EPX was followed by FTIR spectroscopy at regular intervals. SPI‐EPX prepared using epoxy‐based semi‐IPNs of sulfonated polyimide, SPI‐EP(40,50), exhibited higher hydrolytic stability than the phthalic polyimides (five‐membered ring polyimides).The microstructure was analyzed using atomic force microscopy (AFM) in the tapping mode, which demonstrated that SPI‐EP50 exhibited a nanophase that was separated into an essentially reticulated and venous hydrophobic and hydrophilic domains. Transmission electron microscopy (TEM) confirmed widespread and well‐connected hydrophilic domains, proving the higher hydrolytic stability and strong proton‐transporting properties of the SPI‐EPX membrane. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2262–2276, 2008