Preclinical PET Imaging and Toxicity Study of a Ga-Functionalized Polymeric Cardiac Blood Pool Agent.

Cardiac blood pool imaging is currently performed almost exclusively with Tc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope Ga is used, it can be applied repeatedly on the same day-for example, for the detection of bleeding.

Evaluation of hyperbranched polyglycerol for cold perfusion and storage of donor kidneys in a pig model of kidney autotransplantation.

Hyperbranched polyglycerol (HPG) is a biocompatible polyether polymer that is a potential colloid component in a preservation solution for suppressing interstitial edema during cold storage of a donor organ. This study evaluated the outcomes of kidney transplants after cold perfusion and storage with a HPG-based preservation solution (HPGS) in a pig model of kidney autotransplantation. The left kidneys of farm pigs (weighing 35-45 kg) were perfused with and stored in either cold HPGS or standard UW solution (UWS), followed by transplantation to the right side after right nephrectomy.

Polymer-Nanoparticle Interaction as a Design Principle in the Development of a Durable Ultrathin Universal Binary Antibiofilm Coating with Long-Term Activity.

Bacterial attachment and biofilm formation pose major challenges to the optimal performance of indwelling devices. Current coating methods have significant deficiencies including the lack of long-term activity, easy of application, and adaptability to diverse materials. Here we describe a coating method that could potentially overcome such limitations and yield an ultrathin coating with long-term antibiofilm activity.

Oncotically Driven Control over Glycocalyx Dimension for Cell Surface Engineering and Protein Binding in the Longitudinal Direction.

Here we present a simple technique for re-directing reactions on the cell surface to the outermost region of the glycocalyx. Macromolecular crowding with inert polymers was utilized to reversibly alter the accessibility of glycocalyx proteoglycans toward cell-surface reactive probes allowing for reactivity control in the longitudinal direction ('z'-direction) on the glycocalyx. Studies in HUVECs demonstrated an oncotically driven collapse of the glycocalyx brush structure in the presence of crowders as the mechanism responsible for re-directing reactivity.

Hyperbranched polyglycerols: recent advances in synthesis, biocompatibility and biomedical applications.

In the pursuit of dendrimer alternatives, hyperbranched polymers have found increasing interest from academia and industry in a broad range of fields due to their topological and synthetic advantages. Hyperbranched polyglycerol (HPG), as the name implies, is a hyperbranched polymer with about 50-65% dendrimeric structure. Due to its ease in synthesis, globular nature, versatility in terms of functionalization, and superb biocompatibility profiles HPG provides a promising class of materials suitable for numerous applications in nanomedicine and biomedical technologies.

Development of Antifouling and Bactericidal Coatings for Platelet Storage Bags Using Dopamine Chemistry.

Platelets have a limited shelf life, due to the risk of bacterial contamination and platelet quality loss. Most platelet storage bags are made of a mixture of polyvinyl chloride with a plasticizer, denoted as pPVC. To improve biocompatibility of pPVC with platelets and to inhibit bacterial biofilm formation, an antifouling polymer coating is developed using mussel-inspired chemistry.

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats.

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution.

Anti-adhesive antimicrobial peptide coating prevents catheter associated infection in a mouse urinary infection model.

Catheter-associated urinary tract infections (CAUTIs) represent one of the most common hospital acquired infections with significant economic consequences and increased patient morbidity. CAUTIs often start with pathogen adhesion and colonization on the catheter surface followed by biofilm formation. Current strategies to prevent CAUTIs are insufficiently effective and antimicrobial coatings based on antimicrobial peptides (AMPs) hold promise in curbing CAUTIs.

Advantages of replacing hydroxyethyl starch in University of Wisconsin solution with hyperbranched polyglycerol for cold kidney perfusion.

Background: Efficient and effective perfusion during organ procurement is required for the best prevention of donor organ injury preceding transplantation. However, current organ preservation solutions, including hydroxyethyl starch (HES)-based University of Wisconsin (UW) solution, do not always yield the best outcomes. Our previous study demonstrated that replacing HES with hyperbranched polyglycerol (HPG) reduced donor heart injury during cold storage.

Effect of texture of platelet bags on bacterial and platelet adhesion.

Background: Missed detection of Staphylococcus epidermidis contamination in platelet (PLT) storage bags by the standard 24-hour-postcollection BacT/ALERT screening test has been documented. A slow growth rate and the strong tendency of this bacterium to adhere to surfaces can contribute to missed detection of the pathogen.

Study Design And Methods: Topography of two different PLT storage bag surfaces, textured (rough) and smooth surfaces of Terumo 80440 bags (designated A15), was studied.

Choline phosphate functionalized cellulose membrane: A potential hemostatic dressing based on a unique bioadhesion mechanism.

Unlabelled: Wound dressings are a key component in provision of optimal conditions for bleeding control and wound healing. For absorbent dressings, electrostatic interactions are frequently utilized as one of the mechanisms driving dressing adhesion. Herein, a choline phosphate functionalized biocompatible cellulose membrane that can efficiently arrest human red blood cells was developed to have potential application in wound dressing.

Reversible hemostatic properties of sulfabetaine/quaternary ammonium modified hyperbranched polyglycerol.

A library of hyperbranched polyglycerols (HPGs) functionalized with different mole fractions of zwitterionic sulfabetaine and cationic quaternary ammonium ligands was synthesized and characterized. A post-polymerization method was employed that utilized double bond moieties on the dendritic HPG for the coupling of thiol-terminated ligands via UV initiated thiol-ene "click" chemistry. The proportions of different ligands were precisely controlled by varying the ligand concentration during the irradiation process.

Hyperbranched polyglycerol as a colloid in cold organ preservation solutions.

Hydroxyethyl starch (HES) is a common colloid in organ preservation solutions, such as in University of Wisconsin (UW) solution, for preventing graft interstitial edema and cell swelling during cold preservation of donor organs. However, HES has undesirable characteristics, such as high viscosity, causing kidney injury and aggregation of erythrocytes. Hyperbranched polyglycerol (HPG) is a branched compact polymer that has low intrinsic viscosity.

A thermoreversible poly(choline phosphate) based universal biomembrane adhesive.

A new monomer, 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl methacrylate (AEO4 MA), and its direct atom transfer radical polymerization (ATRP) into poly(AEO4 MA), then "clicked" with prop-2-ynyle choline phosphate (CP) to produce a poly(choline phosphate) are described. This polymer exhibits a lower critical solution temperature (LCST) at ≈ 32 °C, and provides a universal thermally reversible biomembrane adhesive, which can rapidly both bind to any mammalian cell membrane and internalize into the cytoplasm of nucleated cells below the LCST. Moving above the LCST reverses cell surface binding.

A pH and thermosensitive choline phosphate-based delivery platform targeted to the acidic tumor microenvironment.

Solid tumors generally exhibit an acidic microenvironment which has been recognized as a potential route to distinguishing tumor from normal tissue for purposes of drug delivery or imaging. To this end we describe a pH and temperature sensitive polymeric adhesive that can be derivatized to carry drugs or other agents and can be tuned synthetically to bind to tumor cells at pH 6.8 but not at pH 7.

Thermal reversal of polyvalent choline phosphate, a multivalent universal biomembrane adhesive.

Multivalent macromolecular associations are widely observed in biological systems and are increasingly being utilized in bioengineering, nanomedicine, and biomaterial applications. Control over such associations usually demands an ability to reverse the multivalent binding. While in principle this can be done with binding site competitive inhibitors, dissociation is difficult in practice due to limited site accessibility when the macromolecule is bound.

Therapeutic cells via functional modification: influence of molecular properties of polymer grafts on in vivo circulation, clearance, immunogenicity, and antigen protection.

Modulation of cell surface properties via functional modification is of great interest in cell-based therapies, drug delivery, and in transfusion. We study the in vivo circulation, immuogenicity, and mechanism of clearance of hyperbranched polyglycerol (HPG)-modified red blood cells (RBCs) as a function of molecular properties of HPGs. The circulation half-life of modified cells can be modulated by controlling the polymer graft concentration on RBCs; low graft concentrations (0.

Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems.

Biodegradable multi-functional polymeric nanostructures that undergo controlled degradation in response to physiological cues are important in numerous biomedical applications including drug delivery, bio-conjugation and tissue engineering. In this paper, we report the development of a new class of water soluble multi-functional branched biodegradable polymer with high molecular weight and biocompatibility which demonstrates good correlation of in vivo biodegradation and in vitro hydrolysis. Main chain degradable hyperbranched polyglycerols (HPG) (20-100 kDa) were synthesized by the introduction of acid labile groups within the polymer structure by an anionic ring opening copolymerization of glycidol with ketal-containing epoxide monomers with different ketal structures.

ATRP synthesis of poly(2-(methacryloyloxy)ethyl choline phosphate): a multivalent universal biomembrane adhesive.

A new monomer, 2-(methacryloyloxy)ethyl choline phosphate, and its direct polymerization into a polyvalent choline phosphate are described, providing a universal biomembrane adhesive exhibiting rapid, strong attachment to any mammalian cell membrane and fast internalization, properties of great value in applications such as tissue engineering and drug delivery.

Antigens protected functional red blood cells by the membrane grafting of compact hyperbranched polyglycerols.

Red blood cell (RBC) transfusion is vital for the treatment of a number of acute and chronic medical problems such as thalassemia major and sickle cell anemia. Due to the presence of multitude of antigens on the RBC surface (~308 known antigens), patients in the chronic blood transfusion therapy develop alloantibodies due to the miss match of minor antigens on transfused RBCs. Grafting of hydrophilic polymers such as polyethylene glycol (PEG) and hyperbranched polyglycerol (HPG) forms an exclusion layer on RBC membrane that prevents the interaction of antibodies with surface antigens without affecting the passage of small molecules such as oxygen, glucose, and ions.

Influence of polymer architecture on antigens camouflage, CD47 protection and complement mediated lysis of surface grafted red blood cells.

Hyperbranched polyglycerol (HPG) and polyethylene glycol (PEG) polymers with similar hydrodynamic sizes in solution were grafted to red blood cells (RBCs) to investigate the impact of polymer architecture on the cell structure and function. The hydrodynamic sizes of polymers were calculated from the diffusion coefficients measured by pulsed field gradient NMR. The hydration of the HPG and PEG was determined by differential scanning calorimetry analyses.

Polyvalent choline phosphate as a universal biomembrane adhesive.

Phospholipids in the cell membranes of all eukaryotic cells contain phosphatidyl choline (PC) as the headgroup. Here we show that hyperbranched polyglycerols (HPGs) decorated with the 'PC-inverse' choline phosphate (CP) in a polyvalent fashion can electrostatically bind to a variety of cell membranes and to PC-containing liposomes, the binding strength depending on the number density of CP groups per macromolecule. We also show that HPG-CPs can cause cells to adhere with varying affinity to other cells, and that binding can be reversed by subsequent exposure to low molecular weight HPGs carrying small numbers of PCs.

Hyperbranched polyglycerols as trimodal imaging agents: design, biocompatibility, and tumor uptake.

Combining various imaging modalities often leads to complementary information and synergistic advantages. A trimodal long-circulating imaging agent tagged with radioactive, magnetic resonance, and fluorescence markers is able to combine the high sensitivity of SPECT with the high resolution of MRI over hours and days. The fluorescence marker helps to confirm the in vivo imaging information at the microscopic level, in the context of the tumor microenvironment.

In vivo circulation, clearance, and biodistribution of polyglycerol grafted functional red blood cells.

The in vivo circulation of hyperbranched polyglycerol (HPG) grafted red blood cells (RBCs) was investigated in mice. The number of HPG molecules grafted per RBC was measured using tritium labeled HPGs ((3)H-HPG) of different molecular weights; the values ranged from 1 × 10(5) to 2 × 10(6) molecules per RBC. HPG-grafted RBCs were characterized in vitro by measuring the electrophoretic mobility, complement mediated lysis, and osmotic fragility.