Nonthermal plasma treatment of polymers modulates biological fouling but can cause material embrittlement.

Plasma-based treatment is a prevalent strategy to alter biological response and enhance biomaterial coating quality at the surfaces of biomedical devices and implants, especially polymeric materials. Plasma, an ionized gas, is often thought to have negligible effects on the bulk properties of prosthetic substrates given that it alters the surface chemistry on only the outermost few nanometers of material. However, no studies to date have systematically explored the effects of plasma exposure on both the surface and bulk properties of a biomaterial. This work examines the time-dependent effects of a nonthermal plasma on the surface and bulk (i.e. mechanical) properties of polymeric implants, specifically polypropylene surgical meshes and sutures. Findings suggest that plasma exposure improved resistance to fibrinogen adsorption and Escherichia coli attachment, and promoted mammalian fibroblast attachment, although increased duration of exposure resulted in a state of diminishing returns. At the same time, it was observed that plasma exposure can be detrimental to the material properties of individual filaments (i.e. sutures), as well as the structural characteristics of knitted meshes, with longer exposures resulting in further embrittlement and larger changes in anisotropic behavior. Though there are few guidelines regarding appropriate mechanical properties of surgical textiles, the results from this investigation imply that there are ultimate exposure limits for plasma-based treatments of polymeric implant materials when structural properties must be preserved, and that the effects of a plasma on a given biomaterial should be examined carefully before translation to a clinical scenario.

A Polymeric Delivery System Enables Controlled Release of Genipin for Spatially-Confined In Situ Crosslinking of Injured Connective Tissues.

An emerging approach toward repair of connective tissues applies exogenous crosslinkers to mechanically augment injured structures in vivo. One crosslinker that has been explored for this purpose is the plant-derived small molecule genipin. However, genipin's high reactivity to primary amines in proteins, small size, and high diffusion coefficient necessitate localizing and controlling its delivery to avoid off-target or adverse effects. In this study, genipin-loaded polymers were evaluated for sustained local administration. Insoluble polymers comprising subunits of α-, ß-, or γ-cyclodextrin, cyclic oligosaccharides possessing increasing cavity sizes, were compared to polymers comprising subunits of the non-cyclic polysaccharide dextran. Polymers made from ß-cyclodextrin showed prolonged genipin release for over ten times longer than polymers made from α- or γ-cyclodextrins or dextran, indicating that genipin possesses molecular affinity for the ß-cyclodextrin cavity. Modeling of complexation between genipin and cyclodextrin hosts supported this finding. Genipin released from all polymers was confirmed to be functional by exogenous collagen crosslinking through fluorometric and mechanical readouts. Co-incubation of genipin-loaded polymers with bovine tendon explants showed genipin crosslink-mediated coloration that was confined to the sites of exposure. Altogether, results indicate that host-guest interactions within a polymeric delivery vehicle can help to control and confine genipin release.