Despite its medical applications, the mechanisms responsible for the osseointegration of bioactive glass (45S5) have yet to be fully understood. Evidence suggests that the strongest predictor for osseointegration of bioactive glasses, and ceramics, with bone tissue as the formation of an apatitic calcium phosphate layer atop the implanted material, with osteoblasts being the main mediator for new bone formation. Most have tried to understand the formation of this apatitic calcium phosphate layer, and other bioresponses between the host and bioactive glass 45S5 using Simulated Body Fluid; a solution containing ion concentrations similar to that found in human plasma without the presence of proteins. However, it is likely that cell attachment is probably largely mediated via the adsorbed protein layer. Plasma protein adsorption at the tissue bioactive glass interface has been largely overlooked. Herein, we compare crystalline and amorphous bioactive glass 45S5, in both melt-derived as well as sol-gel forms. Thus, allowing for a detailed understanding of both the role of crystallinity and powder morphology on surface ions, and plasma protein adsorption. It was found that sol-gel 45S5 powders, regardless of crystallinity, adsorbed 3-5 times as much protein as the crystalline melt-derived counterpart, as well as a greater variety of plasma proteins. The devitrification of melt-cast 45S5 resulted in only small differences in the amount and variety of the adsorbed proteome. Surface properties, and not material crystallinity, play a role in directing protein adsorption phenomena for bioactive glasses given the differences found between crystalline melt-cast 45S5 and sol-gel derived 45S5.

Elastin-like polypeptides (ELPs) are being developed for numerous biomedical applications. There is a limited understanding of ELP biocompatibility, with conflicting results in the literature. Protein adsorption is the fate determining event for blood-contacting biomaterials. The aim of this study is to elucidate the biocompatibility of ELP-based nanoparticles by examining the adsorbed proteome from platelet poor human plasma as a function of the physicochemical properties of these nanoparticles: diameter, amino acid hydrophobicity, and chain length. It was found that all ELP constructs had adsorbed an extremely large amount of albumin and high levels of immunoglobulin G and activated complement factor 3. Variations in the compositions of the proteomes across the eight nanoparticle systems studied were observed for plasminogen, fibronectin, activated fibrinogen, and coagulation modulating antithrombin and alpha2 macroglobulin. Plasma clotting experiments showed that ELP-based nanoparticles slightly inhibited normal blood clotting, with shorter and/or more hydrophilic constructs showing a greater difference from the control than longer or more hydrophobic constructs. These results indicate that ELP nanoparticles, regardless of chain length, particle diameter, or amino acid hydrophobicity, may have the potential to stimulate a humoral immune response via immunoglobulin G and activated complement factor 3 despite the large amounts of albumin adsorbed at the blood-material interface.

Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL), have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol) (1 kDa, PEG) units conjugated to PLL (4.2 and 24 kDa) on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of the adsorbed proteome was similar for all systems. siRNA was effectively encapsulated and released in a sustained manner from all NPs. With 4.2 kDa PLL, cellular uptake was not affected by the presence of PEG, but PEG coating inhibited uptake with 24 kDa PLL NPs. Moreover, 24 kDa PLL systems were cytotoxic and this cytotoxicity was diminished upon PEG incorporation. The overall results identified a BSA-NP coating structure that provided effective siRNA encapsulation while reducing ζ-potential, protein adsorption, and cytotoxicity, necessary attributes for in vivo application of drug-delivery vehicles.