Mussel adhesive proteins contain catechol moiety, which allows the protein to crosslinked, solidify, and adhere to surrounding surfaces even under wet conditions. Incorporating the catechol moiety into polymeric adhesive resulted in bioadhesive, which still functions under wet conditions. However, the adhesive must be oxidized in order to crosslink and adhere to surfaces. The oxidation process of catechol adhesive was proven to produce singlet oxygen, superoxide, and hydrogen peroxide (H₂O₂). These reactive oxygen species, with lack of control, can wreak havoc to the biological system causing poor healing and undesired biological response. Here, we studied the silica particle system as a means to control H₂O₂ concentration. After an exploratory investigation on silica particle synthesis and modification, acid-treated silica particle (AHSi) was developed with a highly hydrophilic surface. We then explore the use of reinforcement phase incorporation, creating particle-adhesive composites and studied the effect which the particle incorporation imparts into the adhesives. The model adhesive is polyethylene glycol functionalized with glutaric acid and dopamine, creating a biodegradable adhesive hydrogel. We demonstrated that incorporation of a model particle, silica particle, into a catechol adhesive resulting in a mechanically stronger adhesive with an increase in stiffness, adhesion strength, and structural integrity even after partially degraded. Moreover, the composite adhesive was gelled faster and degrade slower than native PEG-DA adhesive. The composite also demonstrated a reduction in the concentration of H₂O₂. The particle not only reduces H₂O₂ but also found to be releasing soluble silica in a biologically relevant concentration further improve their bioreactivity. The silica nanoparticle incorporated catechol-based composite demonstrated a reduction in cytotoxicity on rat dermal fibroblast, human keratinocyte, and human tenocyte, three types of cells that react differently to elevated oxidative stress. Interestingly, all cell types have demonstrated an increase in cell proliferation, raising the possibility of developing the composite adhesive further. The last part of the study involved a prediction model that helps narrow down the formulation to be tested in vivo. Full-thickness dermal wound model in mice was utilized to study the predicted formulation. The results from the animal model suggested that PEG adhesive alone can alter the biological response with accelerated wound healing. However, the incorporation of AHSi proved to successfully bridge the gap between accelerated wound healing and better wound remodeling. This dissertation describes various strategies used to tune the H₂O₂ concentration released from catechol adhesives to tune its biological response which involved silica particle modification with minimal change in chemical composition, and the selection of adhesive… Advisors/Committee Members: Bruce P. Lee, Rupak M. Rajachar.