Enzymatic syntheses of unsaturated polyesters based on isosorbide and isomannide

The search for materials produced from renewable sources aiming at the substitution of petroleum‐based derivates is an area of intense investigation. In this work, the enzymatic copolymerization of isosorbide or isomannide with diethyl adipate and fractions of different unsaturated diesters (diethyl itaconate, diethyl fumarate, diethyl glutaconate, and diethyl hydromuconate) were examined using CAL‐B as catalyst. The polyesters prepared using one‐step syntheses were characterized by SEC, NMR, and MALDI‐TOF MS. In addition, syntheses with linear diols were carried out in bulk to evaluate the reactivity of cyclic diols in producing unsaturated polyesters using enzymatic catalysis, as well as to evaluate the occurrence of addition side reactions on the double bonds. Isosorbide and isomannide yielded unsaturated polymers with values in the order of 4,000‐16,000 when fumarate or glutaconate esters were added in 5 mol % ratio against adipate. In all cases MALDI‐TOF confirmed the presence of unsaturated units. Although these polyesters have unreacted double bonds they are prone to crosslinking and ready to further functionalization, like anchoring bioactive molecules. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3881–3891     

Quantitative analysis of complex amino acids and RGD peptides by X‐ray photoelectron spectroscopy (XPS)

The C 1 s, N 1 s, and O 1 s core level binding energies (BEs) of the functional groups in amino acids (glycine, aspartic acid, glutamic acid, arginine, and histidine) with varied side‐chains and cell‐binding RGD‐based peptides have been determined and characterized by X‐ray photoelectron spectroscopy with a monochromatic Al K_α source. The zwitterionic nature of the amino acids in the solid state is unequivocally evident from the N 1 s signals of the protonated amine groups and the C 1 s signature of carboxylate groups. Significant adventitious carbon contamination is evident for all samples but can be quantitatively accounted for. No intrinsic differences in the XP spectra are evident between two polymorphs (α and γ) of glycine, indicating that the crystallographic differences have a minor influence on the core level BEs for this system. The two nitrogen centers in the imidazole group of histidine exhibit an N 1 s BE shift that is in line with previously reported data for theophylline and aqueous imidazole solutions, while the nitrogen and carbon chemical shifts reflect the unusual guanidinium chemical environment in arginine. It is shown that the complex envelopes of C 1 s and O 1 s photoemission spectra for short‐chain peptides can be analyzed quantitatively by reference to the less complex XP spectra of the constituent amino acids, provided the peptides are of high enough purity. The distinctive N 1 s photoemission from the amide linkages provides an indicator of peptide formation even in the presence of common impurities, and variations in the relative intensities of N 1 s were found to be diagnostic for each of the three peptides investigated (RGD, RGDS, and RGDSC). Copyright © 2013 John Wiley & Sons, Ltd.     

Microwave‐Assisted Hydrogel Synthesis: A New Method for Crosslinking Polymers in Aqueous Solutions

It has been found that hydrogels may be formed by microwave irradiation of aqueous solutions containing appropriate combinations of polymers. This new method of hydrogel synthesis yields sterile hydrogels without the use of monomers, eliminating the need for the removal of unreacted species from the final product. Results for two particularly successful combinations, poly(vinyl alcohol) with either poly(acrylic acid) or poly(methylvinylether‐alt‐maleic anhydride), are presented. Irradiation using temperatures of 100–150 °C was found to yield hydrogels with large equilibrium swelling degrees of 500–1000 g g⁻¹. Material leached from both types of hydrogel shows little cytotoxicity towards HT29 cells.     

Nanostructured Materials for Skeletal Repair

The treatment of bone and cartilage defects with bioengineered constructs of artificial scaffolds and autogenous cells became the main challenge of contemporary regenerative medicine. Early defect repair may prevent secondary injury. Recent studies could prove that bone and cartilage cells are sensitive to microscale and nanoscale patterns of surface topography and chemical structure. Nanostructured materials provide an environment for tissue regeneration mimicking the physiological range of extracellular matrix. The article reviews several studies substantiating the superiority of nanostructured materials for bone and cartilage repair along with own results on cell attachment.     

Synthesis and Properties of Dendronized Chitosan

Summary: Chitosan films and microspheres were prepared and their surfaces were functionalized with first generation dendritic molecules. The films were modified by Weisocyanate dendron, while Behera's and bis Behera's amine dendrons were used to modify the microspheres. Prior to dendronization films were prepared by blending chitosan with 18% of polyvinyl pyrrolidone (PVP), and casting the resulting mixture. The degree of dendronization reached was 28%. The microspheres were prepared by coacervation/precipitation, after which the surfaces were activated with either epychlorohydrine (ECH) or 1,4-butanediol diglycidyl ether (BDGE). The oxirane groups were utilized to form covalent bonds between chitosan and dendrons. The degree of dendronization yielded with Behera's amine was 60% for both activating agents. When bis Behera's amine was used, the dendronization reached values of 15 and 21% when ECH or BDGE were used, respectively. The dendronized products were characterized through spectroscopic and microscopic studies and by determination of swelling indexes. Only one of the surfaces was dendronized in every film, which therefore presented a hydrophobic and a hydrophilic surface. Since these films maintain the properties of chitosan, they offer interesting potential as dressings for exuding wounds. The different surfaces make the microspheres potentially applicable as carriers for delivery and controlled release of drugs.     

Synthesis of New Regioselectively Sulfated Hyaluronans for Biomedical Application

Sulfated glycosaminoglycans (GAGs) display various biological effects which are strongly influenced by the degree of sulfation and the position of sulfate groups within the polymer. Hyaluronan, a non-sulfated GAG, represents a readily accessible educt to synthesize structural analogues of sulfated GAGs mimicking their biological activity. Different strategies were developed and evaluated to synthesize hyaluronan sulfates with a free primary hydroxyl group at C-6' and sulfated secondary hydroxyl groups. Applying selective desulfation methods of high-sulfated hyaluronan by means of silylating agents, products regioselectively desulfated at the primary C-6' but also partly the C-4' position were obtained. A pathway using benzoyl ester protecting groups to block the primary hydroxyl function of Hya during the sulfation resulted in a high-sulfated product, functionalized only at the secondary hydroxyl groups.     

Designing of dipeptide‐based oligoconjugates as potential carrier for drug delivery. Pyroglutamil‐S‐glutamic acid bisoligo‐3‐hydroxybutyrates

In the present article, we describe the synthesis and characterization of conjugates based on pyroglutamyl‐S‐glutamic acid and bisoligo‐[R,S]‐3‐hydroxybutyrates (PyGlu‐S_‐Glu_bisOHB) using anionic ring opening polymerization of β‐butyrolactone with a dipeptide bearing two carboxylate groups as potassium salt. The results indicated that the above‐mentioned reaction is accompanied of oligomerization of β‐butyrolactone yielding (3‐hydroxybutyrates) oligomers with crotonate and carboxyl end groups. We report also the end group analysis of the synthesized conjugates using electrospray ionization tandem mass spectrometry (ESI‐MS), the latter confirmed the presence of a mixture of dipeptide conjugate with β‐butyrolactone oligomer chain and β‐butyrolactone homopolymer. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4103–4111, 2008     

MOLECULAR ENGINEERING STUDIES ON NONTHROMBOGENIC BIOMATERIALS--A NOVEL CLASS OF NONTHROMBOGENIC BIOMATERIALS WITH ZWITTERIONIC STRUCTURE OF CARBOXYBETAINES

N,N-dimethyl-N-methacryloyloxyethyl-N-carboxyethyl ammonium (DMMCA) was graft-copolymerized onto the surface of segmented poly(ether urethane) (SPEU) and PE film. The carboxybetaine structure on SPEU and PE film surfaces was confirmed by ATR-FTIR, XPS and water contact angle measurements. Through the experiments with platelet adhesion and protein adhesion assay in vitro, the two materials studied, including poly-DMMCA gel, all show excellent nonthrombogenicity. This confirms once again that the zwitterionic molecular structure on the surfaces of materials is essential for improving their nonthrombogenicity and biocompatibility.     

“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.