Strategies to control the release rate of bioactive signals from tissue engineering scaffolds are essential for tissue regeneration and tissue engineering applications. Here we report on a strategy to achieve temporal control over nanoparticle release from biomaterials using cell-secreted proteases. This cell-triggered release approach utilizes peptides that are degraded by matrix metalloproteinases (MMPs) at different rates to immobilize nanoparticles directly to the biomaterial surface. Thus, the peptide-immobilized nanoparticles are released with temporal control through the action of cellreleased MMPs. We found that release rates of peptide-immobilized nanoparticles were a function of peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and the concentration of proteases used to induce release. Cellular internalization of the peptideimmobilized nanoparticles was also a function of the peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and MMP expression profile of the cells. Similar trends were observed for peptide-immobilized nanoparticles inside micro-porous hydrogels, indicating protease sensitive tethers are effective in controlling release rate and internalization of nanoparticles. Such a temporal delivery strategy of nanoparticles loaded with therapeutic payloads (e.g. protein, DNA, siRNA) can be an ideal means to guide tissue formation.

2,4-dinitrosanisole (DNAN) is an insensitive munitions component replacing conventional explosives. While DNAN is known to biotransform in soils to aromatic amines and azo-dimers, it is seldom mineralized by indigenous soil bacteria. Incorporation of DNAN biotransformation products into soil as humus-bound material could serve as a plausible remediation strategy. The present work studied biotransformation of DNAN in soil and sludge microcosms supplemented with uniformly ring-labeled 14C-DNAN to quantify the distribution of label in soil, aqueous, and gaseous phases. Electron donor amendments, different redox conditions (anaerobic, aerobic, sequential anaerobic-aerobic), and the extracellular oxidoreductase enzyme horseradish peroxidase (HRP) were evaluated to maximize incorporation of DNAN biotransformation products into the non-extractable soil humus fraction, humin. Irreversible humin incorporation of 14C-DNAN occurred at higher rates in anaerobic conditions, with a moderate increase when pyruvate was added. Additionally, a single dose of HRP resulted in an instantaneous increased incorporation of 14C-DNAN into the humin fraction. 14C-DNAN incorporation to the humin fraction was strongly correlated (R2=0.93) by the soil organic carbon (OC) amount present (either intrinsic or amended). Globally, our results suggest that DNAN biotransformation products can be irreversibly bound to humin in soils as a remediation strategy, which can be enhanced by adding soil OC.

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