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Bone metastasis is a frequent occurrence following breast cancer. The bonetumor microenvironment is heterogeneous and complicated to recapitulate. The development of new chemotherapeutics is ineffective partly due to a lack of precise in vitro tissue models. We developed a three-dimensional (3D) bonetumor interface model for customized chemotherapeutic screening. It comprises a plasma-modified electrospun mat seeded with osteoblasts to mimic a bone tissue, with a cell-seeded hydrogel layer containing more and less aggressive or noncancerous cells on top, mimicking the tumor compartment. By screening the model with doxorubicin, we observed different migratory behaviors, with IC 50 values that were largely in accordance with those cell lines' characteristics. Our 3D model reproduces the bone microenvironment and has great potential as a drug screening tool for personalized medicine.

Metastatic cancers can be highly heterogeneous, show large patient variability, and are typically hard to treat due to chemoresistance. Personalized therapies are therefore needed to suppress tumor growth and enhance patient's quality of life. Identifying appropriate patient-specific therapies remains a challenge though, due mainly to non-physiological in vitro culture systems. Therefore, more complex and physiological in vitro human cancer microenvironment tools could drastically aid in the development of new therapies. We developed a plasma-modified, electro-spun 3D scaffold (PP-3D-S) that can mimic the human cancer microenvironment for customized-cancer therapeutic screening. The PP-3D-S were characterized for optimal plasma-modifying treatment and scaffolds morphology including fiber diameter and pore size. PP-3D-S was then seeded with human fibroblasts to mimic a stromal tissue layer; cell adhesion on plasma-modified poly (lactic acid), PLA, electrospun mats vastly exceeded that on untreated controls. The cell-seeded scaffolds were then overlaid with alginate/gelatin-based hydrogel embedded with MDA-MB231 human breast cancer cells, representing a tumor-tissue interface. Among three different plasma treatments, we found that NH3 plasma promoted the most tumor cell migration to the scaffold surfaces after 7 days of culture. For all treated and non-treated mats, we observed a significant difference in tumor cell migration between small-sized and either medium- or large-sized scaffolds. In addition, we found that the PP-3D-S was highly comparable to the standard Matrigel migration assays in two different sets of doxorubicin screening experiments, where a 75% reduction in migration was achieved with 0.5 uM doxorubicin for both systems. Taken together, our data indicate that PP-3D-S is an effective, low-cost, and easy-to-use alternate 3D tumor migration model which may be suitable as a physiological drug screening tool for personalized medicine against metastatic cancers.

Aging (or "hydrophobic recovery") of plasma-modified polymer surfaces has been known and documented in the literature over several decades; to the best of our knowledge, the present study appears to be the first in which this is done for two vastly different rough surface structures: (i) electrospun nanofibrous (NF) mats, and (ii) flat films (FF), for three polymers of well-documented interest in biotechnological applications: poly(lactic acid); poly(urethane); and poly(caprolactone). Two different plasma treatments are applied: low-pressure (LP) radiofrequency (rf) glow discharges in flows of O 2 and NH 3 under mild power conditions. Measured time-dependent surface compositions (from X-ray photoelectron spectroscopy survey spectra) and water contact angles (WCA) were found to tend toward asymptotic limiting values after ca. 30 days of storage in clean air, as previously reported by these and other authors. An entirely novel aspect of this work is to examine and compare time-dependent WCA behaviors of NF and FF samples in terms of Wenzel (W)

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