Recent advances in the production of biomedical systems based on polyhydroxyalkanoates and exopolysaccharides.

In recent years, growing attention has been devoted to naturally occurring biological macromolecules and their ensuing application in agriculture, cosmetics, food and pharmaceutical industries. They inherently have antigenicity, low immunogenicity, excellent biocompatibility and cytocompatibility, which are ideal properties for the design of biomedical devices, especially for the controlled delivery of active ingredients in the most diverse contexts. Furthermore, these properties can be modulated by chemical modification via the incorporation of other (macro)molecules in a random or controlled way, aiming at improving their functionality for each specific application. Among the wide variety of natural polymers, microbial polyhydroxyalkanoates (PHAs) and exopolysaccharides (EPS) are often considered for the development of original biomaterials due to their unique physicochemical and biological features. Here, we aim to fullfil a gap on the present associated literature, bringing an up-to-date overview of ongoing research strategies that make use of PHAs (poly (3-hydroxybutyrate), poly (3-hydroxybutyrate-co-3-hydroxyvalerate), poly (3-hydroxyoctanoate), poly(3-hydroxypropionate), poly (3-hydroxyhexanoate-co-3-hydroxyoctanoate), and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate)) and EPS (bacterial cellulose, alginates, curdlan, pullulan, xanthan gum, dextran, hyaluronan, and schizophyllan) as sources of interesting and versatile biomaterials. For the first time, a monograph addressing the properties, pros and cons, status, challenges, and recent progresses regarding the application of these two important classes of biopolymers in biomedicine is presented.

Synthesis and Self-Assembly of Poly(N-Vinylcaprolactam)-b-Poly(ε-Caprolactone) Block Copolymers via the Combination of RAFT/MADIX and Ring-Opening Polymerizations.

Well-defined amphiphilic, biocompatible and partially biodegradable, thermo-responsive poly(N-vinylcaprolactam)-b-poly(ε-caprolactone) (PNVCL-b-PCL) block copolymers were synthesized by combining reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerizations (ROP). Poly(N-vinylcaprolactam) containing xanthate and hydroxyl end groups (X-PNVCL-OH) was first synthesized by RAFT/macromolecular design by the interchange of xanthates (RAFT/MADIX) polymerization of NVCL mediated by a chain transfer agent containing a hydroxyl function. The xanthate-end group was then removed from PNVCL by a radical-induced process. Finally, the hydroxyl end-capped PNVCL homopolymer was used as a macroinitiator in the ROP of ε-caprolactone (ε-CL) to obtain PNVCL-b-PCL block copolymers. These (co)polymers were characterized by Size Exclusion Chromatography (SEC), Fourier-Transform Infrared spectroscopy (FTIR), Proton Nuclear Magnetic Resonance spectroscopy (1H NMR), UV-vis and Differential Scanning Calorimetry (DSC) measurements. The critical micelle concentration (CMC) of the block copolymers in aqueous solution measured by the fluorescence probe technique decreased with increasing the length of the hydrophobic block. However, dynamic light scattering (DLS) demonstrated that the size of the micelles increased with increasing the proportion of hydrophobic segments. The morphology observed by cryo-TEM demonstrated that the micelles have a pointed-oval-shape. UV-vis and DLS analyses showed that these block copolymers have a temperature-responsive behavior with a lower critical solution temperature (LCST) that could be tuned by varying the block copolymer composition.

Synthesis of amphiphilic pullulan-graft-poly(ε-caprolactone) via click chemistry.

Chemical modification of natural polymers has been commonly employed for the development of new bio-based materials, aiming at adjusting specific properties such as solubility, biodegradability, thermal stability and mechanical behavior. Among all natural polymers, polysaccharides are promising materials, in which biodegradability, processability and bioreactivity make them suitable for biomedical applications. In this context, this work describes the synthesis and characterization of a novel amphiphilic pullulan-g-poly(ε-caprolactone) (Pull-g-PCL) graft copolymer. In a first step, pullulan was chemically modified with 2-bromopropionyl bromide to obtain bromo-functionalized pullulan (PullBr). Then, this precursor was modified with sodium azide, leading to azide pullulan (PullN3). In parallel, propargyl-terminated poly(ε-caprolactone) was prepared via ring-opening polymerization (ROP). These preliminary steps involved the synthesis of azide and alkyne compounds, capable of being linked together via alkyne-azide cycloaddition reaction catalyzed by copper (Cu (I)), which leads to Pull-g-PCL. The chemical structures of the polymers were assessed by Proton Nuclear Magnetic Resonance (1H NMR) and Fourier Transform Infrared (FTIR).