Reconstructing the differentiation niche of embryonic stem cells using biomaterials

The biochemical cues and topographical architecture of the extracellular environment extensively influence ES cell fate. The microenvironment surrounding the developing embryo presents these instructive cues in a complex and interactive manner in order to guide cell fate decisions. Current stem cell research aims to reconstruct this multifaceted embryonic niche to recapitulate development in vitro. This review focuses on 2D and 3D differentiation niches created from natural and synthetic biomaterials to guide the differentiation of ES cells toward specific lineages. Biomaterials engineered to present specific physical constraints are also reviewed for their role in differentiation.     

Antimicrobial anilinium polymers: The properties of poly(N,N‐dimethylaminophenylene methacrylamide) in solution and as coatings

Antimicrobial polymers have been widely reported to exert strong biocidal effects against bacteria. In contrast with antimicrobial polymers with aliphatic ammonium groups, polymers with anilinium groups have been rarely studied and applied as biocidal materials. In this study, a representative polymer with aniline side functional groups, poly(N,N‐dimethylaminophenylene methacrylamide) (PDMAPMA), was explored as a novel antimicrobial polymer. PDMAPMA was synthesized and its physicochemical properties evaluated. The methyl iodide‐quaternized polymer was tested against the Gram‐positive Staphylococcus aureus, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 16–32 and 64–128 μg mL^?1, respectively. Against the Gram‐negative Escherichia coli, the MIC and MBC were both 64–128 μg mL^?1. To broaden the range of applications, PDMAPMA was coated on substrates via crosslinking to endow the surface with contact‐kill functionality. The effect of charge density of the coatings on the antimicrobial behavior was then investigated, and stronger biocidal performance was observed for films with higher charge density. This study of the biocidal behavior of PDMAPMA both in solution and as coatings is expected to broaden the application of polymers containing aniline side groups and provide more information on the antimicrobial behavior of such materials. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1908–1921     

Functionalization of Silk Fibroin with NeutrAvidin and Biotin

New methods are needed to modify silk biomaterials with bioactive molecules for tissue engineering and drug delivery. In the present study, silk fibroin in solution or in microsphere format was coupled with NeutrAvidin via carbodiimide chemistry. Silk fibroin retained its self‐assembly features after reaction. It was found that more than four NeutrAvidin molecules bound to one silk molecule. Non‐specific binding of biotin or NeutrAvidin to silk microspheres could be reduced by pre‐treatment of the microspheres with BSA or post‐treatment with detergent. The NeutrAvidin‐coupled silk microspheres were coupled with biotinylated anti‐CD3 antibody and the functionalized microspheres were able to specifically bind to the CD3 positive T‐lymphocytic cell line Jurkat.

     

Synthesis and properties of a well‐defined glycopolymer via living radical polymerization

A well‐defined glycopolymer was synthesized to investigate its properties. The glycopolymer was obtained with a narrow polydispersity by nitroxide‐mediated radical polymerization of styrene carrying acetylated lactose and by the subsequent deprotection. The cylindrical structure and helical conformation of the polymer were measured by circular dichroism (CD) spectra. The affinities of the polymers towards lectins depended on the degree of polymerization (DP), and the polymers with higher DP showed stronger affinity. Copyright © 2007 John Wiley & Sons, Ltd.     

Effect of Poly(3‐octylthiophene) Doping on the Attachment and Proliferation of Osteoblasts

The effect of doping P3OT with ferric chloride on the attachment and proliferation of MC3T3‐E1 osteoblasts is reported. Cell density and area correlated strongly with doping concentration: cells were larger and exhibited better spreading as doping increased. Cells cultured on undoped P3OT showed a decrease in proliferation between 24 and 48 h followed by a recovery after 72 h. However, this trend diminished with increasing doping concentration, and disappeared completely at the highest dopant level investigated. Analysis of cell‐cell spatial distributions suggested that contact inhibition of proliferation occurred similarly on both undoped and doped P3OT. From these results, FeCl₃‐doping had no significant deleterious effect on attachment or proliferation of osteoblasts in vitro.

     

Controlled release of 2‐heptanone using starch gel and polycaprolactone matrices and polymeric films

Varroa jacobsoni is a parasitic mite that is threatening the honeybee industry in many parts of the world. 2‐Heptanone, a natural product made by honeybees at low concentrations, is effective at elevated concentrations in controlling mite populations in honeybee colonies, especially when released over a 42 day period. An extrusion process was used to encapsulate 14, 18, and 25% 2‐heptanone in a polycaprolactone (PCL) matrix. Less than 18% of the 2‐heptanone was encapsulated in the PCL matrix. The high vapor permeability of PCL to 2‐heptanone resulted in a high flux rate and limited the usefulness of PCL as an encapsulation matrix for controlled‐release devices. A starch gel containing three times its weight in 2‐heptanone was prepared from starch‐based microcellular foam (MCF). The gel had compressive, tensile, and flexural strength values in the range of 0.56 to 1.9 MPa. 2‐Heptanone quickly evaporated from non‐laminated gels. However, when the gel was laminated with different polymeric films, a wide range of flux rates was obtained. The T₅₀ for gels laminated or coated with poly(vinyl alcohol) (PVAL, 99% hydrolyzed) and ethylene‐vinyl alcohol copolymer (EVAL) was 72 and 1030 days, respectively. The most promising film was a starch/glycerol film that released 50% of the 2‐heptanone (T₅₀) in approximately 13 days. Copyright © 2007 John Wiley & Sons, Ltd.     

Coating of titanium implant materials with thin polymeric films for binding the signaling protein BMP2

A fast and simple approach for immobilization using copolymers as interlayers is reported. The synthesized copolymers form stable self-assembled layers on implant materials like, e.g., titanium in a simple coating/drying/washing sequence and have functional groups which can bind proteins from an aqueous solution. The copolymer films have been characterized via ellipsometry and contact angle measurements and were tested for biocompatibility. An immunoassay was used to determine the amount of BMP2 and demonstrated an approximately 10-fold increase as compared to previously used self-assembled monolayers. A BMP2-responsive cell line with luciferase detection was used to determine the biological activity of the bound signaling protein.     

Photo-control of biological systems with azobenzene polymers

Azobenzene-containing polymers offer tremendous advantages and opportunities over other stimuli-responsive materials to interface with biology. Azobenzene's fast, reversible, and innocuous cis–trans geometrical isomerization can be leveraged into dramatic intra- and inter-molecular changes when incorporated in polymeric materials. Azobenzene use has grown from a colorant, through to optical storage materials, and most recently in a variety of biologically themed applications. This review highlights the broad impact this photo-switch has had in recent years and offers a snapshot of the research landscape at the interface between photochemistry and biology. From photo-reversible micelles and peptides to controlled drug release and sensing, the versatility of azobenzene makes it a favored photo-switch found in many emerging applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3058–3070     

Synthesis and Properties of Polycarbosilanes Having Lactose‐Derived Structures

A polycarbosilane having lactose‐derived structures was synthesized, and its thermal property, cytotoxicity, chemical crosslinking, and protein adsorption properties were investigated. The polycarbosilane (PSB‐Lac) was prepared by a thiol‐ene reaction between precursor poly(1‐(3‐butenyl)‐1‐methylsilacyclubane) (PSB) and heptaacetyl lactose that carried a thiol group at the anomeric position, and the successive deprotection of the acetyl groups. The lactose introduction efficiency determined by ¹H NMR measurement was 75%. TGA and DSC revealed that the polymer had a 5 wt% decomposition temperature of 260 °C and glass transition temperature (T_g) of 84 °C, which indicated that PSB‐Lac was a thermally stable polymer. PSB‐Lac had no significant cytotoxicity, which was evaluated by human liver cancer cell line HepG2 cultivation on the polystyrene dishes coated with the polymer. Urethane‐crosslinked PSB‐Lac films were prepared by casting solutions of PSB‐Lac and hexamethylene diisocyanate and heating at 120 °C after evaporation of the solvent. The crosslinked PSB‐Lac showed higher adsorption of bovine serum albumin than the similarly crosslinked polycarbosilane that had a glucose structure (PSB‐Glc). © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2420–2425     

Chemical conjugation of linear and cyclic RGD moieties to a recombinant elastin-mimetic polypeptide--a versatile approach towards bioactive protein hydrogels

An elastin-mimetic polypeptide, (EMM)(7), with the amino-acid sequence GRDPSS [VPGVG VPGKG VPGVG VPGVG VPGEG VPGIG](7) was used for chemical conjugation of various integrin ligands (RGD peptides) to prepare bioactive hydrogels. The chemical approach involved (1) chemical protection of lysine residues with Fmoc or Boc groups, (2) chemical ligation of a protected linear or cyclic RGD ligand, with or without a hexanoic-acid spacer to the glutamic acid residue, (3) deprotection of the lysine functionalities and the RGD moieties and (4) cross-linking to form a bioactive hydrogel. (1)H NMR spectroscopy was used to quantify the multiple steps in the reaction. The chemical protection was found to be between 65 and 93% for Fmoc and Boc, respectively. The ligands studied included linear RGD cell-binding [H-FGRGDS-OH (1-l-RGD), H-Ahx--FGRGDS-OH (2-Ahx-FGRGDS) and a cyclic -H(2)N-(CH(2))(6)COHN-cyclo(-RGDfK-) (H-Ahx-c(-RGDfK-)) peptide also with a hexanoic-acid spacer. Cell adhesion with mouse osteoblast cells was dependent on the ligand type, ligand density and the use of a spacer.     

Synthesis and Characterization of a Biocompatible Copolymer to be Used as Cell Culture Support

Summary: N-isopropylacrylamide (NIPAAm)/butylacrylate (BAc) copolymer was synthesized by emulsion polymerization in order to use it as a cell culture surface for corneal epithelium biosubstitutes. Results showed that the obtained polymers were thermosensitive hydrogels. The copolymer was characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and swelling degree. 3T3 Swiss cells were used as feeder layers and they were used to test the cytotoxic effect of the hydrogels. The conditions to isolate, cultivate, expand and cryo-preserve human oral mucosal cells were established and analysis of several morphological and immuno-histochemical characteristics of the cultivated oral mucous were made.     

“Bio”‐Macromolecules: Polymer‐Protein Conjugates as Emerging Scaffolds for Therapeutics

Polymer‐protein conjugates are biohybrid macromolecules derived from covalently connecting synthetic polymers with polypeptides. The resulting materials combine the properties of both worlds: chemists can engineer polymers to stabilize proteins, to add functionality, or to enhance activity; whereas biochemists can exploit the specificity and complexity that Nature has bestowed upon its macromolecules. This has led to a wealth of applications, particularly within the realm of biomedicine. Polymer‐protein conjugation has expanded to include scaffolds for drug delivery, tissue engineering, and microbial inhibitors. This feature article reflects upon recent developments in the field and discusses the applications of these hybrids from a biomaterials standpoint.

     

Conjugation of arginine–glycine–aspartic acid peptides to thermoreversible N‐isopropylacrylamide polymers

Thermoreversible polymeric biomaterials are finding increased acceptance in tissue engineering applications. One drawback of the polymers is their synthetic nature, which does not allow direct interaction of mammalian cells with the polymers. This limitation may be alleviated by grafting arginine–glycine–aspartic acid (RGD) containing peptides onto the polymer backbone to facilitate interactions with cell‐surface integrins. Toward this goal, N‐isopropylacrylamide (NiPAM)‐based thermoreversible polymers containing amine‐reactive N‐acryloxysuccinimide (NASI) groups were synthesized. Conjugation of RGD‐containing peptides to polymers was demonstrated with ¹H NMR spectroscopy and reverse‐phase high‐pressure liquid chromatography. The conjugation reaction was optimal at 4 °C and pH of 8.0, and increased with the increasing NASI content of polymers. With a peptide grafting ratio of 0.25 mol %, there was no significant change in the lower critical solution temperature of the polymers. Finally, the NASI‐containing polymers, cast as films, on tissue culture polystyrene, were shown to conjugate to RGD‐containing peptides and support C2C12 cell attachment. We conclude that NASI‐containing thermoreversible polymers are amenable for grafting biomimetic peptides to impart cell adhesiveness to the polymers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3989–4000, 2003     

Chemoenzymatic synthesis of glycoconjugate polymers starting from nonreducing disaccharides

Here we report the chemoenzymatic synthesis and recognition function of glycoconjugate polymers carrying nonreducing disaccharides [α-D -glucopyranosyl-(1-1)-α-D -glucopyranoside (trehalose) and α-D -galactopyranosyl-(1-1)-α-D -glucopyranoside (Gal-type trehalose)]. The lipase-catalyzed esterification of the disaccharides with divinyl sebacate is completely selective at the primary Glc 6-OH position of trehalose and at the Gal 6-OH position of Gal-type trehalose. The resultant vinyl esters can be polymerized to yield glycoconjugate polymers with poly(vinyl alcohol) backbones. The interactions of the glycoconjugate polymers with lectins (concanavalin A and Bandeiraera simplicifolia) are amplified because of the glycocluster effect. The polymer carrying pendant α-D -galactopyranosyl-(1-1)-α-D -glucopyranoside shows inhibition activity against Shiga toxin-1 based on a stereochemical structure similar to that of globosyl Gb2 disaccharide. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4598–4606, 2004     

生物医用磷脂化聚氨酯的设计、制备与性能

聚氨酯因其具有优异的力学性能和良好的生物相容性广泛地应用于医疗领域.但医用聚氨酯常常会引起蛋白吸附、血小板激活、凝血、血栓和补体激活等不良生物学反应,使其应用受到限制.仿生物膜的磷脂表面被认为是和人体最亲和的表面,聚氨酯磷脂化是提高医用聚氨酯材料生物相容性的非常有效的手段之一.近年来国内外课题组在生物医用磷脂化聚氨酯的设计、制备与生物相容性等方面开展了大量的工作,取得了重要的研究进展.本文综述了磷脂改进医用聚氨酯的最新研究成果,指出含氟磷脂化聚氨酯和可降解的磷脂聚氨酯因其优异的性能,代表了该领域的发展方向并具有重要的应用前景.     

Biomaterials made of bile acids

The use of natural compounds in the preparation of new materials can improve the biocompatibility of the materials and avoid any potential toxicity of the degradation products when used for biomedical applications. Bile acids are amphiphilic molecules biosynthesized in the liver. They are used to prepare various polymers and oligomers. These polymers made of bile acids are promising materials in both biomedical and pharmaceutical fields.     

Synthesis of networked polymers with lithium counter cations from a difunctional epoxide containing poly(ethylene glycol) and an epoxide monomer carrying a lithium sulfonate salt moiety

Poly(ethylene glycol)‐based networked polymers that had lithium sulfonate salt structures on the network were prepared by heating a mixture of poly(ethylene glycol) diglycidyl ether (PEGGE), poly(ethylene glycol) bis(3‐aminopropyl) terminated (PEGBA), and an ionic epoxy monomer, lithium 3‐glycidyloxypropanesulfonate (LiGPS). Flexible self‐standing networked polymer films showed high thermal stability, low crystallinity, low glass transition temperature, and good mechanical strength. The materials were ion conductive at room temperature even under a dry condition, although the ionic conductivity was rather low (10^?6 to 10^?5 S/m). The ionic conductivity increased with the increase in temperature to above 1 × 10^?4 S/m at 90 °C. The film samples became swollen by immersing in propylene carbonate (PC) or PC solution of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). The samples swollen in PC showed higher ionic conductivity (ca.1 × 10^?3 S/m at room temperature), and the samples swollen in LiTFSI/PC showed much higher ionic conductivity (nearly 1 S/m at room temperature). © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3113–3118, 2010     

Vinyl polymers as non-viral gene delivery carriers: current status and prospects

Since the first application of polymers as non-viral gene delivery systems in 1965 by Vaheri and Pagano using functionalised dextran (A. Vaheri and J. S. Pagano, "Infectious poliovirus RNA: a sensitive method of assay", Virology 1965, 27, 434-6), a large number of different polymers have been developed, studied and compared for application as DNA carriers. Vinyl-based polymers are one type of polymers that have gained considerable interest. The interest in developing this particular type of polymer is partly related to the straightforward way in which large amounts of these polymers can be prepared by radical (co)polymerisation. This opens up a path for establishing a wide range of structure-property relations using polymer libraries. The present review aims to give an overview of past and ongoing research using vinyl-based gene delivery systems. The application of cationic, neutral and zwitterionic polymers as DNA carriers is summarised and discussed. [structure: see text] Chemical structure of DEAE-functionalised dextran.     

Synthesis of polymers having a phospholipid polar group connected to a poly(oxyethylene) chain and their protein adsorption-resistance properties

New methacrylates having a phospholipid polar group which was connected to various lengths of poly(oxyethylene) chains to form a polymerizable group (MEOnPC) were synthesized. The MEOnPC could polymerize with n-butyl methacrylate (BMA) in ethanol using a conventional radical polymerization technique. The unit mole fraction of MEOnPC in the polymer corresponded to that in the feed monomer solution. The MEOnPC polymers were soluble in ethanol, insoluble in water, but swelled in water and became hydrated. On the surface of a poly(BMA) membrane coated with MEOnPC, the phosphorylcholine groups of the MEOnPC unit present were determined by x-ray photoelectron spectroscopy. As a fundamental evaluation for biomedical materials, adsorption of one of the plasma proteins, fibrinogen, on acrylic beads coated with the MEOnPC polymers was evaluated. The amount of fibrinogen adsorbed on the MEOnPC polymer was smaller than that on the original acrylic beads, poly(BMA) and poly(2-hydroxyethyl methacrylate). The increase in the MEOnPC unit mole fraction in the polymer showed more effective protein adsorption-resistant properties. © 1996 John Wiley & Sons, Inc.