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This study aims to shed light on the relationship between drug content and adhesive properties in drug-in-adhesive transdermal patch, and to elucidate molecular mechanisms from the perspective of polymer chain mobility. Lidocaine was selected as model drug. Two acrylate pressure sensitive adhesives (PSAs) with different polymer chain mobility were synthesized. Tack adhesion, shear adhesion and peel adhesion of PSAs with 0, 5%, 10%, 15% and 20% w/w lidocaine contents were tested. Polymer chain mobility was determined by rheology and modulated differential scanning calorimetry experiments. Drug-PSA interaction was analyzed by FT-IR. The effect of drug content on free volume of PSA were determined by positron annihilation lifetime spectroscopy and molecular dynamics simulation. It was found that the polymer chain mobility of PSA was increased with increasing drug content. Due to the variation of polymer chain mobility, tack adhesion increased, and shear adhesion decreased. It was proved that interactions between polymer chains were destroyed by drug-PSA interactions, free volume between polymer chains was expanded, resulting in the increase of polymer chain mobility. We can conclude that the effect of drug content on polymer chain mobility should be considered, when designing a transdermal drug delivery system with controlled and satisfactory adhesion., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Tissue cells are known to respond to the stiffness of the polymer substrate on which they are grown. It has been suggested that material stiffness influences the composition of the protein layer that adsorbs to the material surface, which affects subsequent cell behavior. Previously, the stiffness of a biomaterial elastomer formed from an acrylated star-poly(d,l lactide-co-ε-caprolactone) was found to influence both fibroblast proliferation as well as the adsorption of certain proteins. However, it remained unresolved as to whether material stiffness influenced protein adsorption from serum supplemented environments and which protein(s) may have been responsible for the difference in fibroblast proliferation. Using quantitative proteomics, we show that polymer stiffness influenced the composition of the protein layers that adsorb from serum supplemented media. Fetuin A was identified as a protein that influenced fibroblast proliferation and, when combined with basic fibroblast growth factor as a medium supplement, improved fibroblast proliferation over 14days. This study is the first to correlate cell proliferation to surface adsorbed fetuin A and presents the potential new application for fetuin A as biomaterial coating or surface modifier. This work also demonstrates a novel application of quantitative proteomics for the investigation of competitive protein adsorption to biomaterial surfaces., Statement of Significance: Cells are able to respond to the stiffness of their material substrate, but the method by which they sense material stiffness is still under investigation. Previously, material stiffness was found to impact the individual adsorption of fibronectin, a protein associated with cell attachment; however, it was unclear if stiffness was able to affect protein adsorption in environments with multiple proteins. This study shows that material stiffness affects the compositions of protein layers adsorbed from supplemented media, and suggests that cells may sense material stiffness via the adsorbed protein layer. Interestingly, fetuin A was found to be affecting cell proliferation and not fibronectin. Finally, this research demonstrates the use of relative quantitation proteomics as a potentially powerful method to improve biomaterial compatibility., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Poly(trimethylene carbonate) (PTMC) with molecular weights greater than 100 kg/mol is known to degrade readily in vivo while PTMC of less than 70 kg/mol is resistant to degradation. The reason for the molecular weight dependent degradation rate of PTMC is unclear, and may be due to differences in macrophage behavior or enzyme adsorption or activity. Macrophage number and production of reactive oxygen species (ROS) and esterase were measured when cultured on 60 and 100 kg/mol PTMC. Cholesterol esterase and lipase were adsorbed to 60 and 100 kg/mol PTMC and mass and viscoelastic properties of the adsorbed enzyme layers were measured. No significant differences were observed in macrophage number or production of degradative species. Significant differences were measured in mass, shear modulus and viscosity of the adsorbed cholesterol esterase layer, suggesting that the cholesterol esterase is adsorbing in a different conformation on the 60 and 100 kg/mol PTMC. Despite similar bulk moduli, the surface modulus of 60 kg/mol PTMC was significantly lower than 100 kg/mol. It is proposed that the difference in surface stiffness and polymer chain flexibility affect the arrangement of water bound to and freed from the polymer chains during adsorption, thus affecting enzymatic adsorption, conformation, and activity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cells are known to respond differently when grown on materials of varying stiffness. However, the mechanism by which a cell senses substrate stiffness is unknown. Lower crosslink density elastomers formed from acrylated star-poly(d,l lactide-co-ϵ-caprolactone) have previously been shown to support higher smooth muscle cell proliferation in in vitro culture. This difference in growth was hypothesized to be due to differences in protein adsorption that resulted from differences in polymer chain mobility at the surface. Therefore, layer mass and viscoelastic properties were measured for HSA, IgG, fibronectin, vitronectin, and serum supplemented media adsorbed to elastomers of two crosslink densities. Significantly more fibronectin adsorbed to the lower crosslink density surface while significantly more IgG adsorbed to the higher crosslink density surface. Furthermore, differences in fibronectin and IgG layer shear moduli were observed, suggesting that there was a difference in the conformation of the adsorbed protein. ATR-FTIR analysis showed that the lower crosslink density elastomer absorbed more surface water. The increased amount of water may cause greater entropic gains upon protein adsorption to the lower crosslink density surface, which increases total protein adsorption from serum and may cause differences in protein conformation and thus cell behavior., (Copyright © 2013 Elsevier Ltd. All rights reserved.)