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Synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. However, polymeric biomaterials are lacking imaging contrast properties for deep tissue imaging. This report details the synthesis and characterization of a suite of aryl-iodo monomers, which were used to prepare iodinated polyesters using a pre-functionalization approach. Commercially available 4-iodo-phenylalanine or 4-iodobenzyl bromide served as the starting materials for the synthesis of three iodinated monomeric moieties (a modified lactide, morpholine-2,5-dione, and caprolactone), which under a tin-mediated ring-opening polymerization (ROP), generated their respective polyesters (PE) or poly(ester amides) (PEA). An increase in X-ray intensity of all synthesized iodine-containing polymers, in comparison to non-iodinated poly(lactic acid) (PLA), validated their functionality as radio-opaque materials. The iodinated-poly(lactic acid) (iPLA) material was visualized through varying thicknesses of chicken tissue, thus demonstrating its potenial as a radio-opaque biomaterial.

To address a need for highly X-ray opaque biodegradable materials, a series of poly(e-caprolactone) derivatives were prepared using oxime post-polymerization modification to conjugate two different iodinated hydroxylamines. These materials were synthesized with up to 32 wt. % iodine content and demonstrated improved X-ray contrast relative to both the ketone precursors and previously reported monoiodinated materials. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016

Several synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. Polymeric biomaterials and metals are commonly used imaging agents and can assist in the monitoring of therapy response, migration, degradation, changes in morphology, defects, and image-guided surgery. In comparison to metals, most bio and synthetic polymers lack inherent imaging properties. Polymeric biomaterials, specifically polyesters, have gained a considerable amount of attention due to their unique properties including biocompatibility, biodegradation, facile synthesis, and modification capability. Polyester implants and nanomaterials are available on the market or are in clinical trials for many applications including: dental implants, cranio-maxilofacial implants, soft tissue sutures and staples, abdominal wall repair, tendon and ligament reconstruction, fracture fixation devices, and coronary drug eluting stents. This review aims to provide a summary of the recent developments of polyesters with bioimaging contrast properties. The three main approaches to prepare bioimaging polyesters (coating, encapsulation, and functionalization) are discussed in depth. Furthermore, commonly used imaging modalities including X-ray computed tomography, magnetic resonance imaging, ultrasound, fluorescence, and radionucleotide polyester contrast agents are highlighted. In each section, examples of impactful bioimaging polyesters in the five major imaging modalities are evaluated.

Degradable, amphiphilic graft copolymers of poly- (e-caprolactone)-graft-poly(ethylene oxide), PCL-g-PEO, were synthesized via a grafting onto strategy taking advantage of the ketones presented along the backbone of the statistical co- polymer poly(e-caprolactone)-co-(2-oxepane-1,5-dione), (PCL- co-OPD). Through the formation of stable ketoxime ether link- ages, 3 kDa PEO grafts and p-methoxybenzyl side chains were incorporated onto the polyester backbone with a high degree of fidelity and efficiency, as verified by NMR spectroscopies and GPC analysis (90% grafting efficiency in some cases). The resulting block graft copolymers displayed significant thermal differences, specifically a depression in the observed melting transition temperature, Tm, in comparison with the parent PCL and PEO polymers. These amphiphilic block graft copolymers undergo self-assembly in aqueous solution with the P(CL-co- OPD-co-(OPD-g-PEO)) polymer forming spherical micelles and a P(CL-co-OPD-co-(OPD-g-PEO)-co-(OPD-g-pMeOBn)) forming cylindrical or rod-like micelles, as observed by transmission electron microscopy and atomic force microscopy. V C 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3553-3563, 2010

Because of the significant interest in synthetic polymer systems with increasing degrees of complexity, we have focused attention upon the development of chemistries for the conversion of polyester backbones into functional materials. Facile conjugation strategies involving the reactions of both aminooxy and sulfonyl hydrazide nucleophiles with poly(e-caprolactone-co-2-oxepane-1,5-dione) (P(CL-co-OPD)) are studied as general methodologies employing a sequential vs a single-step approach. Agreement between product and feed stoichiometries was achieved with both of the model hydroxylamines, O-dodecylhydroxylamine or O-benzylhydroxylamine. However, when sequential reactions were performed with either hydroxylamine together with dansyl hydrazide, considerable deviations in the product composition, relative to the reaction feed stoichiometries, were noted. For a sequential series of reactions, the successful use of aminooxy and sulfonyl hydrazide molecules required ketoxime ether formation prior to sulfonyl hy...

Novel polystyrene nanoparticles were synthesized by the controlled intra- molecular crosslinking of linear polymer chains to produce well-defined single-mole- cule nanoparticles of varying molecular mass, corresponding directly to the original linear precursor chain. These nanoparticles are ideal to study the relaxation dynam- ics/processes of high molecular mass polymer melts, as the high degree of intramolec- ular crosslinking potentially inhibits entanglements. Both the nanoparticles and their linear analogs were characterized by measuring their intrinsic viscosity, hydrody- namic radius (Rh), and radius of gyration (Rg). The ratio Rg/Rh was computed to char- acterize the molecular architecture of the nanoparticles in solution, revealing a shift toward the constant density sphere limit with increasing crosslink density and molec- ular mass. Further, confirming particulate behavior, Kratky plots obtained from neu- tron scattering data show a shift toward particle-like nature. The rheological behav- ior of the particles was found to be strongly dependent on both the extent of intramo- lecular crosslinking and molecular mass, with a minimal viscosity change at low crosslinking levels and a gel-like behavior evident for a large degree of crosslinking. These and other results suggest the presence of a secondary mode of polymer relaxa- tion/movement besides reptation, which in this case, is influenced by the total num- ber of crosslinked loops present in the nanoparticle. V C 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1930-1947, 2006

Traditionally the dispersion of particles in polymeric materials has proven difficult and frequently results in phase separation and agglomeration. We show that thermodynamically stable dispersion of nanoparticles into a polymeric liquid is enhanced for systems where the radius of gyration of the linear polymer is greater than the radius of the nanoparticle. Dispersed nanoparticles swell the linear polymer chains, resulting in a polymer radius of gyration that grows with the nanoparticle volume fraction. It is proposed that this entropically unfavorable process is offset by an enthalpy gain due to an increase in molecular contacts at dispersed nanoparticle surfaces as compared with the surfaces of phase-separated nanoparticles. Even when the dispersed state is thermodynamically stable, it may be inaccessible unless the correct processing strategy is adopted, which is particularly important for the case of fullerene dispersion into linear polymers.

The effect of nanoscopic, shape persistent polystyrene (PS) nanoparticles on the rheological properties of linear PS is studied and a dramatic viscosity reduction is observed. This is an ideal blend which simplifies enthalpic interactions between the components and can be used to delineate the effect of particle size on the properties of the blends. Homogeneous blends are assured through small-angle neutron scattering (SANS) experiments which establish the absence of phase segregation (depletion flocculation) in the nanoparticle-polymer blend. We previously found that nanoparticles reduce the viscosity of high molecular mass linear PS when the interparticle gap is smaller than the linear polymer size. In the present study, we find that such confinement of entangled polymers is necessary for the viscosity reduction since lower concentrations provide a viscosity increase. Furthermore, the behavior is found to be dependent on the presence or absence of entanglements and confinement is seemingly not important for unentangled polymers. It is proposed that constraint release caused by the addition of nanoparticles is responsible for some of the observed changes in viscosity although it is suspected this is a very complicated phenomenon and introduction of free volume by the nanoparticles is certain to play a key role.

Surface-initiated living free-radical polymerization is employed in a multistep procedure to prepare hollow polymeric nanocapsules. Initially, trichlorosilyl-substituted alkoxyamine initiating groups are attached to the surface silanol groups of silica nanoparticles. This surface layer of initiating groups is then used to grow functionalized linear chains leading to a core–shell morphology. The choice of functional groups is governed by their ability to undergo facile crosslinking reactions, with both active ester and benzocyclobutene groups being examined. Under either chemical or thermal conditions, the reaction of these functionalities gives a crosslinked polymeric shell that is covalently attached to, and surrounds, the central silica core. Removal of the silica core with HF then gives the hollow polymeric nanocapsules, which are stable under solvent dissolution and thermal treatment because of their crosslinked structure. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1309–1320, 2002

When biodegradable polyester devices, like sutures and screws, are implanted into the body, it is very challenging to image them in deep tissue, monitor their degradation, and detect defects. We report our recent findings on non-invasive deep tissue imaging of polyester degradation, stability and integrity using an iodinated-polycaprolactone (i-P(CLcoOPD)) X-ray imaging contrast agent. The results of experiments performed with i-P(CLcoOPD) demonstrate the feasibility to quantify in-situ polyester degradation in vitro and in vivo using rats. We also demonstrate that X-ray imaging could be used to identify and quantify physical defects, such as cracks, in polymeric implants using rabbit animal models. This approach enables non-invasive monitoring of polyester materials and is expected to become an important technology for improving the imaging of polymers at clinically relevant depths.

We show it is possible to assemble nanoparticle-polymer layers in a controllable manner dictated by the difference in nano-object morphology and dielectric properties. A thin (10-100 nm) layer of the two components is spin coated onto a solid substrate and the system thermally aged to activate a cross-linking process between polymer molecules. The nanoparticles segregate to the solid substrate prior to complete cross-linking if entropic forces are dominant or to the air interface if dielectric (surface energy) forces are properly tuned. Subsequent layers are then spin coated onto the layer below, and the process is repeated to create layered structures with nanometer accuracy useful for tandem solar cells, sensors, optical coatings, etc. Unlike other self-assembly techniques the layer thicknesses are dictated by the spin coating conditions and relative concentration of the two components.

A novel approach is presented for the controlled intramolecular collapse of linear polymer chains to give well-defined single-molecule nanoparticles whose structure is directly related to the original linear polymer. By employing a combination of living free radical polymerization and benzocyclobutene (BCB) chemistry, nanoparticles can be routinely prepared in multigram quantities with the size being accurately controlled by either the initial degree of polymerization of the linear chain or the level of incorporation of the BCB coupling groups. The latter also allows the cross-link density of the final nanoparticles to be manipulated. In analogy with dendritic macromolecules, a significant reduction of up to 75% in the hydrodynamic volume is observed on going from the starting random coil linear chains to the corresponding nanoparticles. The facile nature of the living free radical process also permits wide variation in monomer selection and functional group incorporation and allows novel macromolecular architectures to be prepared. Furthermore, the use of block copolymers functionalized with benzocyclobutene groups in only one of the blocks gives, after intramolecular collapse, a hybrid architecture in which a single linear polymer chain is attached to the globular nanoparticle.

Intramolecular H-bonding has been shown to be a powerful tool in increasing the performance of alkoxyamine initiators for nitroxide mediated living free radical polymerizations.