| Nanofilm biomaterials formed by layer-by-layer (LbL) assembly are important systems for a variety of cell-contacting biomedical and biotechnological applications. Mechanical rigidity and bioactivity are two key film properties known to significantly influence the behavior of contacting cells. Cells tend to attach more efficiently to "harder" films, and bioactive films may be achieved through the incorporation of proteins, peptides, or drugs within the film architecture. A key challenge is to realize films that are simultaneously rigid and bioactive. Chemical cross-linking of the polymer framework --- the standard means of increasing film rigidity --- often leads to enhanced cell attachment, but can have deleterious effects on bioactivity. In particular, cross-linking steps can deactivate embedded biomolecules, limit their mobility, and/or diminish the rate of film biodegradation, thus limiting the extent of cell-bioactive species interaction. This work first presents a strategy to decouple mechanical rigidity and bioactivity, potentially enabling nanofilm biomaterials that are both mechanically rigid and bioactive. The approach is based on selectively cross-linking the outer region of the film, to promote cell attachment, while keeping the film interior "soft", to promote cellular interaction with bioactive species. Next, this surface cross-linking protocol is extended to films assembled on the commonly used biomedical materials poly(L-lactic acid) and poly(lactic-co-glycolic acid), with an eye on eventual tissue engineering applications. Film assembly and cross-linking extent are characterized via quartz crystal microgravimetry with dissipation (QCM-D) and Fourier transform infrared spectroscopy in attenuated total reflection mode (FT1R-ATR). Film growth in porous PLGA scaffolds is monitored by fluorescence microscopy using a fluorescently labeled polymer. The last phase of this work measures the attachment and metabolic activity of pre-osteoblastic MC3T3-El cells on nanofilm biomaterials. Overall, this work shows that (1) covalent chemical cross-linking can be confined to the surface region of thin polyelectrolyte films, (2) the resultant mechanical rigidity lies between that of the native and fully cross-linked films, and (3) the attachment and metabolic activity of cells contacting surface cross- linked films are enhanced compared to cells on native files, to a level comparable to that of a fully cross-linked film. |
