Cytocompatible Polymers Research Articles

Design of Intelligent Interface Based on Cytocompatible Polymers for Control on Cell Function

Bioinspired polymeric biomaterials with excellent cytocompatibility have been designed in this study. 2-Methacryloyloxyehtyl phosphorylcholine (MPC) is a phospholipid polymer and an essential polymeric biomaterial, which has been used in various biomedical and pharmaceutical applications including implantable medical devices. Furthermore, it is a methacrylate monomer unit and can be copolymerized with other vinyl monomers via conventional radical polymerization. The water-solubility of MPC polymers depends on the molecular composition and molecular weight of the polymers. PMB is a water-soluble polymer copolymerized with hydrophobic n-butyl methacrylate, and can be used as a solubilizing agent for poorly soluble drugs. The phospholipid polymers showed low cytotoxicity, and the solubilized drugs effectively not only penetrated into the cells but also into the surrounding tissues. In addition, the water-soluble MPC polymer containing a phenylboronic acid moiety was observed to spontaneously form polymeric hydrogels with polyol compounds. The reversible polymer hydrogels were used as artificial extracellular matrices for cell immobilization and cell engineering. Polymeric biomaterials with intelligent interfaces might be explored as innovative techniques for application in pharmaceutical and life sciences.

Water-Soluble and Cytocompatible Phospholipid Polymers for Molecular Complexation to Enhance Biomolecule Transportation to Cells in Vitro.

Water-soluble and cytocompatible polymers were investigated to enhance a transporting efficiency of biomolecules into cells in vitro. The polymers composed of a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit, a hydrophobic monomer unit, and a cationic monomer unit bearing an amino group were synthesized for complexation with model biomolecules, siRNA. The cationic MPC polymer was shown to interact with both siRNA and the cell membrane and was successively transported siRNA into cells. When introducing 20–50 mol% hydrophobic units into the cationic MPC polymer, transport of siRNA into cells. The MPC units (10–20 mol%) in the cationic MPC polymer were able to impart cytocompatibility, while maintaining interaction with siRNA and the cell membrane. The level of gene suppression of the siRNA/MPC polymer complex was evaluated in vitro and it was as the same level as that of a conventional siRNA transfection reagent, whereas its cytotoxicity was significantly lower. We concluded that these cytocompatible MPC polymers may be promising complexation reagent for introducing biomolecules into cells, with the potential to contribute to future fields of biotechnology, such as in vitro evaluation of gene functionality, and the production of engineered cells with biological functions.

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

AbstractMucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered‐in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water‐soluble, cytocompatible polymers are prepared via an anionic ring‐opening polymerization of a bicyclic β‐lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well‐defined polymers are mucoadhesive as documented in single‐molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers.

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties.

Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered-in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water-soluble, cytocompatible polymers are prepared via an anionic ring-opening polymerization of a bicyclic β-lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well-defined polymers are mucoadhesive as documented in single-molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers.

Determination of association constants between water-soluble phospholipid polymer bearing phenylboronic acid group and polyol compounds for reversible formation of three-dimensional networks

To develop a reversible forming polymer network system, a polymer complexation was conducted between water-soluble and cytocompatible polymers, namely poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV) and poly(vinyl alcohol) (PVA). The two polymers spontaneously form hydrogel upon mixing. The association constant depended on the chemical structure of the polyol compounds and the aggregation of the PMBV. Compared to the association constants of PVA to PMBV, d-glucose and D-sorbitol have smaller and larger association constants, respectively, which is in good accord with the dissociation phenomenon of PMBV/PVA hydrogels. In conclusion, consideration of the association constants between the PMBV and polyol compounds is important for obtaining good reversibility of a polymer hydrogel system.

Photoinduced inhibition of DNA unwinding in vitro with water-soluble polymers containing both phosphorylcholine and photoreactive groups

Nile blue (NB)-tagged DNA helix-targeting amphiphilic photoreactive 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, poly(MPC-co-3-methacryloyloxy-2-hydroxypropyl-4-oxybenzophenone-co-2-trimethylammonium ethyl methacrylate chloride) (PMHT–NB), containing a cationic group to facilitate cell membrane penetration and a benzophenone (BP) group to promote photoinduced conjugation with DNA helix was synthesized using radical polymerization method. Ultraviolet light (UV)-visible light absorption spectra of PMHT–NB showed absorption peaks at wavelengths 254, 289, and 600nm, suggesting successful incorporation of BP and NB groups. PMHT–NB was highly sensitive to photoirradiation with UV irradiation at the second level, as confirmed based on the degradation spectra of UV absorption peaks for the BP group in PBS (pH=7.4). PMHT–NB showed good solubility in both aqueous solution and in ethanol. In a cell culture medium containing 10mg/mL PMHT–NB, the NB group showed fluorescence peaks at an emission wavelength of 650nm and excitation wavelength of 633nm. PMHT–NB also showed low cytotoxicity and good cell membrane permeability toward cancerous HeLa cells. Further, photoinduced PMHT–NB effectively inhibited the unwinding of a molecular beacon with a hairpin structure, indicating that synthetic photoreactive MPC polymers photoregulated the unwinding of DNA. Statement of SignificanceNatural and synthetic genetic hybrid biomaterials consisting of well-designed polymers loaded with oligonucleotide fragments are considered as an attractive alternative to conventional transgene systems and chemical methods for precisely and rapidly modulation of intracellular gene expression. Containing versatile functional moieties, the effectiveness of well-designed cytocompatible polymers themselves without oligonucleotide fragments on gene regulation is rarely investigated. In the present study, a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer composed of a tumor/DNA-targeting moiety and photo-controllable unit demonstrated low cytotoxicity, rapid cell membrane permeability and effective inhibitive ability on DNA unwinding under a light irradiation. The synthetic polymer was considered as promising material to effectively inhibit intracellular partial DNA unwinding for cancer/gene therapy.

Human mesenchymal stem cell behavior on segmented polyurethanes prepared with biologically active chain extenders.

The development of elastomeric, bioresorbable and biocompatible segmented polyurethanes (SPUs) for use in tissue-engineering applications has attracted considerable interest because of the existing need of mechanically tunable scaffolds for regeneration of different tissues, but the incorporation of osteoinductive molecules into SPUs has been limited. In this study, SPUs were synthesized from poly (ε-caprolactone)diol, 4,4'-methylene bis(cyclohexyl isocyanate) using biologically active compounds such as ascorbic acid, L-glutamine, β-glycerol phosphate, and dexamethasone as chain extenders. Fourier transform infrared spectroscopy (FTIR) revealed the formation of both urethanes and urea linkages while differential scanning calorimetry, dynamic mechanical analysis, X-ray diffraction and mechanical testing showed that these polyurethanes were semi-crystalline polymers exhibiting high deformations. Cytocompatibility studies showed that only SPUs containing β-glycerol phosphate supported human mesenchymal stem cell adhesion, growth, and osteogenic differentiation, rendering them potentially suitable for bone tissue regeneration, whereas other SPUs failed to support either cell growth or osteogenic differentiation, or both. This study demonstrates that modification of SPUs with osteogenic compounds can lead to new cytocompatible polymers for regenerative medicine applications.

Optimized sirolimus-eluting stent by coating asymmetrically with biodegradable and cytocompatible polymers

Optimized sirolimus-eluting stent by coating asymmetrically with biodegradable and cytocompatible polymers

Cytocompatibility of polymer-based periodontal bone substitutes in gingival fibroblast and MC3T3 osteoblast cell cultures

ObjectivesInflammatory periodontal diseases are accompanied by destruction of periodontal tissue and alveolar bone. Infrabony lesions can be regenerated with adequate bone substitutes, which require high biocompatibility of the material. MethodsTo rate the biocompatibility of nine polymeric periodontal bone substitutes (Bio 1–Bio 9), cell viability and cytotoxicity assays were performed. For viability, human gingival fibroblasts (HGFs) and MC3T3 osteoblasts were cultured on the bone substitutes. For cytotoxicity, biomaterial extracts were prepared by incubation with culture medium for maximally 28days, and cells were exposed to the extracts for 1day. Polymers Bio 1 to Bio 5 were prepared by solvent casting, Bio 6 to Bio 9 by photopolymerization of the monomers at wavelengths of 400–500nm in the presence of a suitable photoinitiation system. ResultsBio 1, Bio 3, Bio 4, Bio 5, and Bio 7 showed moderate to excellent cytocompatibility for both HGFs and osteoblasts in viability tests. Together with the results of the cytotoxicity assays, four of the nine tested polymers were considered cytocompatible: Bio 1 (poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate; PVB)), Bio 4 and Bio 5 (functionalized oligolactones), and, to a limited degree, Bio 7 (urethane methacrylate). Except for Bio 7, the cytocompatible polymers showed intermediate water contact angles (74–85°) and therefore moderate to low hydrophilicity. SignificanceThe non-cross-linked polymers Bio 1, Bio 4, or Bio 5, and the photopolymerized polymeric network Bio 7 display good/excellent cytocompatibility and are therefore potential candidates for tissue engineering in alveolar bone substitution.