Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials

In recent years, intelligent hydrogels which can change their swelling behavior and other properties in response to environmental stimuli such as temperature, pH, solvent composition and electric fields, have attracted great interest. The hydrogels based on polysaccharides incorporated with thermo-responsive polymers have shown unique properties such as biocompatibility, biodegradability, and biological functions in addition to the stimuli-responsive characters. These "smart" hydrogels exhibit single or multiple stimuli-responsive characters which could be used in biomedical applications, including controlled drug delivery, bioengineering or tissue engineering. This review focuses on the recent developments and future trends dealing with stimuli-responsive hydrogels based on grafting/blending of polysaccharides such as chitosan, alginate, cellulose, dextran and their derivatives with thermo-sensitive polymers. This review also screens the current applications of these hydrogels in the fields of drug delivery, tissue engineering and wound healing.     

Novel porphyrin-incorporated hydrogels for photoactive intraocular lens biomaterials

Novel surface-modified hydrogel materials have been prepared by binding charged porphyrins TMPyP (tetrakis(4-N-methylpyridyl)porphyrin) and TPPS (tetrakis(4-sulfonatophenyl)porphyrin) to copolymers of HEMA (2-hydroxyethyl methacrylate) with either MAA (methacrylic acid) or DEAEMA (2-(diethylamino)ethyl methacrylate). The charged hydrogels display strong electrostatic interactions with the appropriate cationic or anionic porphyrins to give materials which are intended to be used to generate cytotoxic singlet oxygen (1O2) on photoexcitation and can therefore be used to reduce postoperative infection of the intraocular hydrogel-based replacement lenses that are used in cataract surgery. The UV/vis spectra of TMPyP in MAA:HEMA copolymers showed a small shift in the Soret band and a change from single exponential (161 micros) triplet decay lifetime in solution to a decay that could be fitted to a biexponential fit with two approximately equal components with tau = 350 and 1300 micros. O2 bubbling reduced the decay to a dominant (90%) component with a much reduced lifetime of 3 micros and a minor, longer lived (20 micros) component. With D2O solvent the 1O2 lifetime was measured by 1270 nm fluorescence as 35 micros in MAA:HEMA, compared to 67 mus in solution, although absorbance-matched samples showed similar yield of 1O2 in the polymers and in aqueous solution. In contrast to the minor perturbation in photophysical properties caused by binding TMPyP to MAA:HEMA, TPPS binding to DEAEMA:HEMA copolymers profoundly changed the 1O2 generating ability of the TPPS. In N2-bubbled samples, the polymer-bound TPPS behaved in a similar manner to TMPyP in its copolymer host; however, O2 bubbling had only a very small effect on the triplet lifetime and no 1O2 generation could be detected. The difference in behavior may be linked to differences in binding in the two systems. With TMPyP in MAA:HEMA, confocal fluorescence microscopy showed significant penetration of the porphyrin into the core of the polymer film samples (>150 microm). However, for TPPS in DEAEMA:HEMA copolymers, although the porphyrin bound much more readily to the polymer, it remained localized in the first 20 microm, even in heavily loaded samples. It is possible that the resulting high concentration of TPPS may have cross-linked the hydrogels to such an extent that it significantly reduced the solubility and/or diffusion rate of oxygen into the doped polymers. This effect is significant since it demonstrates that even simple electrostatic binding of charged porphyrins to hydrogels can have an unexpectedly large effect on the properties of the system as a whole. In this case it makes the apparently promising TPPS/DEAEMA:HEMA system a poor candidate for clinical application as a postoperative antibacterial treatment for intraocular lenses while the apparently equivalent cationic system TMPyP/MAA:HEMA displays all the required properties.     

Alginate hydrogels incorporating neomycin or propolis as potential dressings for diabetic ulcers: Structure,swelling, and antimicrobial barrier properties

Alginate hydrogels have many attractive characteristics for potential use as wound dressing materials. However, they are not considered to possess any intrinsic activity against microbial infection, often present in neuropathic wounds. To overcome this, the effect of incorporating neomycin or propolis in alginate hydrogels was investigated, both by direct blending alone and also by further addition of loaded alginate microparticles prepared by the extrusion dripping method. The morphological, microstructural, thermal, mechanical, and swelling properties of each film were evaluated, as well as particle size distribution and antimicrobial penetration analysis. Microparticle size was considered suitable for drug delivery applications and incorporation in hydrogel films. The presence of neomycin and propolis, in both blended and microparticle form, interfered with film properties leading to hydrogels with different characteristics. All samples showed swelling degrees up to 100% and mechanical and thermal properties suitable for application as wound dressings. In addition, all samples acted as barriers to microbial penetration.     

Design of lactide copolymers as biomaterials

A very important goal of researchers today is providing poly(L -lactide) (PLA)-based polymers with controllable degradation profiles, various (soft or elastic) mechanical properties, reactivity for chemical modification, and other functionalities while keeping the favorable characteristics of PLA. This article concerns the synthetic methods and properties of the following novel lactide copolymers: (1) random and block copolymers of depsipeptide and L -lactide with reactive (ionic) side-chain groups, (2) comb-type PLA and branched PLA, and (3) PLA-grafted polysaccharide and PLA with terminal saccharide residues. Poly(depsipeptide-random-L -lactide)s and polydepsipeptide-block-poly(L -lactide)s with reactive (ionic) side-chain groups should be useful for the preparation of matrices and microspheres with reactive surfaces because of their amphiphilic structures. Comb-type PLA and branched PLA show lower crystallinities than linear PLA. PLA-grafted polysaccharide should be useful for the preparation of matrices with various microstructures and mechanical and degradation properties through the introduction of hydrophilic segments. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 453–462, 2004     

Hydroxyapatite/polyurethane composites as promising biomaterials

The biomaterials are intended to augment or replace the function of tissues or organs in human body. Every year millions of people require soft- or hard-tissue regeneration worldwide. Polymers and their composites are a large class of biomaterials appreciated for tissue regeneration. Polyurethane (PUR) is an organic synthetic multifunctional polymer with established biomedical applications. The hydroxyapatite (HA) is one of the biocompatible ceramic materials similar to natural bone material. The amalgamation of hydroxyapatite with polyurethane enhances the bioactivity of final product along with the combination of individual properties. Here, we review the synthesis, characterization, and applications studies of HA/PUR-based biomaterials. We initiate this review with a brief and representative compilation of the chemical composition and methods of preparation for HA/PUR biomaterials. Then, moving ahead, first, we review the simple HA/PUR biomaterials and use of PUR templates. Second, we review the significance of modified HA and PUR in these biomaterials. Third, we discuss the potential of bio-based PUR and inclusion of third constituent in the HA/PUR biomaterials. Then, we appraise the involvement of trace nutrient in deposition of HA on PUR scaffolds. Finally, we consider the other expedient applications of HA/PUR composites such as drug delivery system and sorbent of pollutants.     

Copolymers of N-alkylacrylamides as thermosensitive hydrogels

Many of the N-alkyl substituted acrylamide polymers can manifest a lower critical solution temperature (LCST) in aqueous solutions. The LCST of such polymers can be easily varied by a free radical copolymerization of the appropriate comonomers. Natural compounds such as bile acids can be introduced into such polymers to modify the LCST and aggregation behavior and to render the material both thermo- and pH-sensitivity.     

Injectable hydrogels as unique biomedical materials

A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.     

Potential applications of fluorhydroxyapatite as biomaterials in medicine

The present work was undertaken to investigate the bioactivity and cytotoxicity of fluorhydroxyapatite ceramics. The bioactivity was evaluated by in vitro testing in simulated body fluid (SBF), in which ion concentrations are almost identical with inorganic ion concentrations of human blood plasma. Pellets of FA, HA and FHA were immersed in SBF for 48 hours, 1 week and 4 weeks at 36.5°C. Changes of the surface microstructure of the samples were observed by scanning electron microscopy (SEM). 48 hours and one week immersion in SBF did not result in any substantial progress in bioactivity. After 4 weeks in SBF a new biologically active layer was created on the surface of the biomaterials. In addition, the embryonal mouse fibroblast cell line NIH-3T3 was used for a comparative study of basal cytotoxicity of FHA, HA and FA discs. The sensitivity of these cells for tested biomaterials was evaluated on the basis of two cytotoxic end points: cell proliferation and cell morphology. The basal cytotoxicity of FHA, FA and HA discs was measured by a direct contact method. After 24, 48 and 72 hours, the cell growth was evaluated by direct counting of non-affected cells and cells treated by biomaterials. After 72 hours of biomaterials treatment, about 25% inhibition of cell number and unchanged morphology was found.      

Advancement of chitin and chitosan as promising biomaterials

Biopolymers like cellulose, polysaccharides, chitosan, starch, chitin, and alginates have sparked an increasing curiosity in creating natural replacements for synthetic polymers during the last several decades. Chitin is a major part of fungi’s cell walls, the crustaceans’ exoskeletons, like lobsters, crabs, and shrimps, cephalopod beaks, the radulae of mollusks, and fish and lissamphibians scales. Since the late 1970 s, biopolymer chitosan has gathered interest in basic science and applied research due to its incredible macromolecular framework, physicochemical properties, and biological activities, which differ from those of synthetic polymers. Chitin and derivatives thereof have practical usages in chemistry, the agriculture sector, medicine, cosmetics, as well as textile and paper industries. Chitosan has also received a lot of recent interest in the fields of dentistry, ophthalmology, veterinary science, biomedicine, the drink industry, hygiene and personal care, catalysis, chromatography, sewage treatment, and biotechnology. Numerous fundamental investigations have been conducted on chitin and chitosan. This article presents a short compact summary of research over the last two decades in an attempt to highlight the works on chitin and chitosan applications.     

Polyacrylamide hydrogels as substrates for studying bacteria

Polyacrylamide hydrogels can be used as chemically and physically defined substrates for bacterial cell culture, and enable studies of the influence of surfaces on cell growth and behaviour.     

Iodinated polyesters as a versatile platform for radiopaque biomaterials

The design of polymeric biomaterials with long‐lasting X‐ray contrast could advance safe and effective implants and contrast agents. Herein, a new set of wholly aliphatic, iodinated polyesters are synthesized and evaluated as high‐contrast biomaterials and nanoparticle contrast agents for general computed tomography imaging. A single iodinated monomer is used to synthesize a variety of aliphatic polyesters with tunable thermal and mechanical properties. These iodinated polyesters are end‐functionalized with a photocurable methacrylate group, which allows easy processability. The resulting materials exhibit no cytotoxicity and are radiopaque, containing over 40% iodine by weight after processing. The polymers can be formulated into lipid–polymer hybrid nanoparticles using a modified nanoprecipitation method. Initial studies indicate that these nanoparticles show good continual contrast over 60 minutes with no uptake into the kidneys. The work presented here illustrates a novel platform for iodinated polyesters that exhibit high radiopacity and processability, low cost, and no cytotoxicity. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2171–2177     

Glycosyl-nucleoside fluorinated amphiphiles as components of nanostructured hydrogels

The synthesis of two novel glycosyl-nucleoside fluorinated amphiphiles (GNFs) derived from the 2H,2H,3H,3H-perfluoro-undecanoyl hydrophobic chain is described. The GNF amphiphiles, which feature either β-d-glucopyranosyl or β-d-lactopyranosyl moieties linked to a thymine base via a 1,2,3 triazole linker, were prepared using a ‘double click’ chemistry route. Surface tension measurements, gelation properties, and TEM studies show that GNFs spontaneously assemble into supramolecular structures. Similarly to their hydrocarbon analogues (GNLs), the GNFs have unique gelation properties in water. A minimum hydrogelation concentration of 0.1% (w/w), was determined in the case of the β-d-glucopyranosyl derivative. Cell viability studies indicate that fluorocarbon GNF 5 was not toxic for human cells (Huh7), whereas hydrocarbon analogue GNL is toxic above 100 μm.     

Photosensitive peptide hydrogels as smart materials for applications

Photosensitive supramolecular peptide hydrogels with the gelators forming by the integration of photosensitive moieties and peptides have been briefly summarized the hydrogelation capabilities, the expressing manner serving as smart materials, and practical applications.     

Polymeric materials as biomaterials under particular consideration of biodegradable polymers

Biomaterials may be defined as artificial materials which fulfill the mechanical requirements and interact with the biosystem they are in contact with in same way as a natural material would react in the same place. While the requirements of mechanical properties can be reached by suitable organo-polymeric and inorganic materials the interfacial biocompatiblity is neither understood in all its complexity nor can be fulfilled by any of the applied materials. Surface modification and characterization with greatest scrutiny and the observation of the answer of selected parameters of the biosystem are a subject of utmost interest. A few examples will be presented. In the long range, however, it has to be considered that any material is degraded and hence should present continuously a renewable biocompatible surface. On the other hand, materials are desired which deliberately are biodegradable. Presently available materials are polylactides and copolymers. An alternative could be presented by polydepsipeptides because of two reasons, (i) the local concentration of acid formed upon degradation would be reduced as compared to polylactides which in certain cases might be advantageous and (ii) the aminoacid units could carry side groups with bioactive molecules attached. Therefore, a new method of acylation of an aminoacid with a hydroxyacid is presented as well as the cyclisation to result in the cyclic depsipeptide and the polymerisation to yield the polydepsipeptide. The microstructure of the polymers, the thermal properties and the degradation behaviour is presented.     

壳聚糖/海藻酸盐作为新型止血材料的研究进展

有效止血是减轻患者痛苦,降低死亡率的关键,止血材料必须具备良好的止血性、生物相容性、可生物降解、无毒副作用等优点。天然海洋多糖高分子化合物壳聚糖、海藻酸盐作为性能卓越的生物材料已广泛的应用在医学领域。尤其是它们具有良好的生物相容性、生物可降解性、突出的止血效果和抗菌性等特性,对于伤口的愈合有促进作用,是极好的止血材料。本文主要针对这两种海洋高分子化合物作为止血材料的研究进展进行了综述,并对今后的研究重点进行展望。     

Dentin-desensitizing biomaterials

Dentin hypersensitivity (DH) associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration. Medication, filling repair, laser irradiation, crown therapy, and desensitizing toothpaste are standard clinical treatment strategies, but unsatisfactory treatment modalities are marked by long-term administration, poor dentinal tubule closure, microleakage, and the development of secondary caries. To improve the treatment efficiency of DH, numerous organic or inorganic biomaterials have been developed to relieve toothache and reverse the instability of desensitization. Biomaterials are expected to participate in dental remineralization to achieve desensitization. This review discusses various biomaterials for DH therapy based on different desensitization mechanisms, including dentinal tubule closure and dental nerve blockade, and presents a perspective on the underlying future of dentin regeneration medicine for DH therapy.     

海藻酸-壳聚糖-海藻酸凝胶离子取代机理

研究了海藻酸-壳聚糖-海藻酸(ACA)凝胶的离子取代机理.光学显微镜照相法证实ACA离子取代过程中溶胶-凝胶相界面的存在.动边界模型描述ACA离子取代凝胶对二价离子的取代动力学过程,结果表明,模型可靠.离子取代凝胶对二价离子的取代属于颗粒扩散控制机理.与离子交换树脂比较,ACA离子取代速率要快得多,ACA离子取代过程不同于传统离子交换树脂离子交换过程,它是金属离子在溶胶凝胶相转移过程中的取代过程;ACA是一种崭新的离子移变凝胶型离子吸附剂.     

Use of hydrogels as corneal inlays for refractive surgery

A novel hydrogel has been used for intracorneal implantation, in order to correct refractive errors of the eye. Our hydrogel is a polyanionic copolymer of acrylonitrile and sodium methallylsulfonate material (AN 69, made by HOSPAL, France). We describe here its formation, chemico-physical and biological properties (in vitro and in vivo), and its biomechanical behaviour when implanted into the cornea.     

Dendritic macromers as in situ polymerizing biomaterials for securing cataract incisions

Dendritic macromers are attractive macromolecules for hydrogel formation since high cross-linking densities at low polymer concentration can be obtained, varied physical properties can be observed based on the macromer structure, and low viscous aqueous solutions can be injected in an in vivo site of irregular shaped to form a well-integrated polymer network. A peptide dendron possessing terminal cysteine residues was synthesized and characterized. When this peptide dendron was mixed with poly(ethylene glycol dialdehyde) in aqueous solution at pH = 7.4, a hydrogel spontaneously formed as a consequence of thiazolidine linkages between the macromers. Such in situ polymerized hydrogels are of interest for tissue engineering and wound-repair applications. To evaluate the potential use of this hydrogel sealant in ophthalmic surgeries, a 3-mm clear corneal incision (i.e., the wounds created during a typical cataract surgery) was successfully sealed.