Intrahepatic islet transplantation provides a potentially more benign alternative to pancreatic transplantation. However, islet transplants are associated with limited engraftment potential. This inefficiency is likely at least partially attributable to the isolation process, which removes islets from their native environment. Isolation not only disrupts the internal vascularization and innervation of islets, but also fundamentally changes interactions between islet cells and macromolecules of the extracellular matrix (ECM). Signaling interactions between islet cells and ECM are known to regulate multiple aspects of islet physiology, including survival, proliferation, and insulin secretion. Although it is highly likely that disruptions to these interactions during isolation significantly affect transplant outcomes, the true implications of these conditions are not well understood. The following article reviews current understandings and uncertainties in islet-ECM interactions and explains their potential impact on posttransplant engraftment. Topics covered include matrix and receptor compositions in native islets, effects of isolation and culture on islet-ECM interactions, and potential for postisolation restoration of islet-ECM interactions. Greater understanding in these areas may help to reduce isolation and transplantation stresses and improve islet engraftment.

Peptide amphiphile molecules (PAs) developed in our laboratory self‐assemble from aqueous media into three‐dimensional networks of bioactive nanofibers. Multiple non‐covalent interactions promote assembly of the supramolecular nanofibers and ultimately determine the bulk physical properties of the macroscopic gels. In this study, we use oscillatory rheology, Fourier‐transform infrared spectroscopy, and circular‐dichroism spectroscopy to better understand the assembly mechanism of a typical PA molecule known as PA‐1. Self‐assembly of PA‐1 is triggered by counterion screening and stabilized by van der Waals and hydrophobic forces, ionic bridging, and coordination and hydrogen bonding. The concentration, electronic structure, and hydration of counterions significantly influence self‐assembly and gel mechanical properties.

No abstract

Recent advances in nanotechnology and molecular self-assembly may provide novel solutions to current cell transplantation deficiencies. Heparin-binding peptide amphiphiles (HBPAs) self-assemble from aqueous media into nanofibers that bind growth factors through interactions with the bioactive polymer heparin. In this report, we demonstrate that delivery of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) from HBPA scaffolds significantly increases blood vessel density in the mouse omentum over control scaffolds without growth factors (P<0.0005) and significantly enhances islet engraftment. Diabetic recipients transplanted with 250 isologous islets and HBPA scaffolds containing VEGF/FGF-2 achieved normoglycemia at a higher rate (78%) than control animals receiving identical scaffolds without growth factors (30%; P<0.05) or growth factors alone (20%). These data indicate that the enhanced engraftment can be attributed to specific growth factor effects that were made possible by the delivery mechanism of HBPA nanostructures.

No abstract

Dendron rod–coil molecules (DRCs) spontaneously assemble into birefringent gel‐forming networks when added to styrene in small amounts. It is shown that DRC gel derived polystyrene (PS) has greater birefringence than the PS homopolymer when drawn under similar conditions.The dispersed DRC nanophase is responsible for a 70 % increase in impact strength over the PS homopolymer, as well as interesting fracture behavior (see Figure).

Nanoparticulate imaging agents and therapeutics have proven to be valuable tools in preclinical cardiovascular disease research. Because of their distinct properties and significant functional versatility, nanoparticulate imaging agents afford certain capabilities that are typically not provided by traditional small molecule agents. This review is the second in a two-part series covering nanoparticulate imaging agents and theranostics. It highlights current examples of radiolabeled nanoparticulate probes in preclinical cardiovascular research and demonstrates their utility in applications such as blood pool imaging and molecular imaging of ischemia, angiogenesis, atherosclerosis, and inflammation. These agents provide valuable insight into the molecular and cellular mechanisms of cardiovascular disease and illustrate both the limitations and the significant potential of nanoparticles in diagnostic and therapeutic applications. Further technologic development to improve performance, address safety concerns, and fulfil regulatory obligations is required for clinical translation of these emergent technologies.

Imaging agents made from nanoparticles are functionally versatile and have unique properties that may translate to clinical utility in several key cardiovascular imaging niches. Nanoparticles exhibit size-based circulation, biodistribution, and elimination properties different from those of small molecules and microparticles. In addition, nanoparticles provide versatile platforms that can be engineered to create both multimodal and multifunctional imaging agents with tunable properties. With these features, nanoparticulate imaging agents can facilitate fusion of high-sensitivity and high-resolution imaging modalities and selectively bind tissues for targeted molecular imaging and therapeutic delivery. Despite their intriguing attributes, nanoparticulate imaging agents have thus far achieved only limited clinical use. The reasons for this restricted advancement include an evolving scope of applications, the simplicity and effectiveness of existing small-molecule agents, pharmacokinetic limitations, safety concerns, and a complex regulatory environment. This review describes general features of nanoparticulate imaging agents and therapeutics and discusses challenges associated with clinical translation. A second, related review to appear in a subsequent issue of JNM highlights nuclear-based nanoparticulate probes in preclinical cardiovascular imaging.