Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging.

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.

Recent Advances in Polyesters for Biomedical Imaging.

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.

Non-invasive deep tissue imaging of iodine modified poly(caprolactone-co-1-4-oxepan-1,5-dione) using X-ray.

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.

Cross-linked and functionalized polyester materials constructed using ketoxime ether linkages.

A modular and simple approach to the graft functionalization and cross-linking of ketone-containing poly(ε-caprolactone)s has been investigated for the preparation of novel gel and nanoparticulate materials. Poly(ε-caprolactone--2-oxepane-1,5-dione) (P(CL--OPD)), was grafted by reaction with 1-aminooxydodecane and cross-linked by reaction with 1,6-bis(aminooxy)hexane, each at room temperature in tetrahydrofuran at 1 and 10 wt% polymer in the absence of an acid catalyst, and at 1, 5 and 10 wt% polymer in the presence of -toluenesulfonic acid. The grafting process served as a model system for the cross-linking reactions, affording products that were fully characterizable and retained the physical properties of (P(CL--OPD)), with a slight increase in measured molecular weight and characteristic spectroscopic signatures for the dodecyl chains and the newly introduced ketoxime functionalities. Early stages of the intermolecular cross-linking were followed by gel permeation chromatography and atomic force microscopy. Ultimately, insoluble, but tetrahydrofuran-swollen gelled products were obtained, which were characterized by infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. These materials exhibited interesting melting transition profiles, undergoing melting at lower temperatures and broader temperature ranges than observed for their polymer precursors. This study represents an advance in the development of rapid and efficient chemistry for the preparation of functional and robust hydrolytically-degradable polymer materials with degradable linkages.