Specific cell adhesion and osteogenicity are both crucial factors for the long-term success of titanium implants. In this work, two mussel-derived bioactive peptides were designed to one-step dual-biofunctionalization of titanium implants via robust catechol/TiO coordinative interactions. The highly biomimetic peptides capped with integrin-targeted sequence or osteogenic growth sequence could efficiently improve the biocompatibilities of titanium implants and endow the implants with abilities to induce specific cell adhesion and enhanced osteogenicity. More importantly, rationally combined use of the two biomimetic peptides indicated an enhanced synergism on osteogenicity, osseointegration and finally the mechanical stability of Ti implants in vivo. Therefore, the highly biomimetic mussel-derived peptides and the dual-functional strategy in this study would provide a facile, safe, and effective means for improving clinical outcome of titanium-based medical implants.

The interaction between synthetic polymer nanoparticles (NPs) and biomacromolecules (e.g. proteins, lipids and polysaccharides) can profoundly influence the NPs fate and function. Polysaccharides (e.g. heparin/heparin sulfate) are a key component of cell surfaces and the extracelluar matrix and play critical roles in many biological processes. We report a systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides by ITC, SPR and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications. The interaction between acrylamide nanoparticles (~30 nm) and heparin is mainly enthalpy driven with submicromolar affinity. Hydrogen bonding, ionic interactions and dehydration of polar groups are identified to be key contributions to the affinity. It has been found that high charge density and cross linking of the NP can contribute to high affinity. The affinity and binding capacity of heparin can be significantly diminished by an increase in salt concentration while only slightly decreased with an increase of temperature. A striking difference in binding thermodynamics has been observed when polymer nanoparticle’s main component is changed from acrylamide (enthalpy driven) to N-isopropylacryalmide (entropy driven). This change in thermodynamics leads to different responses of these two types of polymer NPs to salt concentration and temperature. Select synthetic polymer nanoparticles have also been shown to inhibit protein-heparin interactions and thus offer the potential for therapeutic applications.

Biochemical diversity of venom extracts often occurs within a small number of shared protein families. Developing a sequestrant capable of broad-spectrum neutralization across various protein isoforms within these protein families is a necessary step in creating broad-spectrum antivenom. Using directed synthetic evolution to optimize a nanoparticle (NP) formulation capable of sequestering and neutralizing venomous phospholipase A (PLA), we demonstrate that broad-spectrum neutralization and sequestration of venomous biomacromolecules is possible via a single optimized NP formulation. Furthermore, this optimized NP showed selectivity for venomous PLA over abundant serum proteins, was not cytotoxic, and showed substantially long dissociation rates from PLA. These findings suggest that it may show efficacy as an in vivo venom sequestrant and may serve as a generalized lipid-mediated toxin sequestrant.

A functional nanoparticle with light-triggered charge reversal based on a protected amine-bridged polysilsesquioxane was designed. An emulsion- and amine-free sol-gel synthesis was developed to prepare uniform nanospheres. Photolysis of suspensions of these nanoparticles results in a reversal of the ζ potential. This behavior has been used to trigger nanoparticle self-assembly, nanocomposite hydrogel formation, and nanoparticle release, showing the potential of this material in nanoscale manipulation and nanoparticle therapy.

Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.