A novel 3D in vitro tissue model for bone‐metastasized breast cancer: A preclinical tool in drug discovery and testing

Abstract

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.

Wetting and aging behaviors for several O2 and NH3 plasma treated nanofibrous and flat film polymer materials: A comparison

“…[ 19,21 ] In those studies, as in the above‐cited work, [ 30,31 ] plasmas that yielded O‐containing surface functionalities all proved successful in promoting cell adhesion and proliferation, including certain ultra‐thin plasma polymer coatings, “PP‐EL” and “L‐PPE:O.” [ 21 ] Regarding N‐containing functionalities, NH 3 and “PP‐AAm” yielded similarly favorable results, while “L‐PPE:N” (LP plasma polymerized ethylene with N doping) inexplicably led to high WCA values and mediocre cell adhesion/proliferation, outcomes comparable to those with untreated (“control”) NF mats. In those earlier reports, [ 19,21 ] we did not speculate about possible reasons, but in light of Section 3.3.2. ), particularly of Table 2, we may now do so: wettability strongly depends upon the relevant plasma‐induced surface chemistry, which is reproducibly unfavorable in the case of L‐PPE:N coated PLA NF mats.…”

“…The principal methods used to characterize the NF mats and flat film (FF) samples were: SEM; (ii) XPS; (iii) static WCA goniometry. These have already been presented in detail elsewhere, [ 19,21 ] so we limit our description below only to the essentials. The surfaces of polymeric NF mats and FFs were examined at different magnifications by SEM using a Hitachi model TM3030plus instrument at a working distance of 2 mm, voltage of 15 kV, and 30 µA beam current. Samples were mounted on a holder using double‐sided adhesive tape and adjusted at the targeted distance.…”

“…SEM; (ii) XPS; (iii) static WCA goniometry. These have already been presented in detail elsewhere, [ 19,21 ] so we limit our description below only to the essentials.…”

“…Figure 2 shows (a) a scanning electron micrograph (SEM) and (b) a fiber diameter distribution curve of electrospun poly(lactic acid) (PLA), a NF mat of "medium" (600-800 nm) fiber diameter sizes [19] ; we specify "medium" henceforth, to distinguish from "small" (200-400 nm) and "large" diameters (1-2 µm) also discussed in Mohseni Garakani et al [19] As described in recent work from these laboratories [19][20][21] and others, [3] such highly porous (90% or more empty space) NF mats are increasingly being used for various biotechnological applications. [3,21] Those include ones in which the structures serve as 3D scaffolds for tissue engineering, situations in which complete wetting of all surfaces by water-based suspensions of living cells, followed by their adherence and proliferation on the inner NF surfaces, are essential for success. A fabrication step immediately following the electrospinning itself involves LT plasma treatment of the 3D mat, either by (i) grafting or (ii) plasma polymerization [9,10,22] ; this, required to increase the surface energy, γ s and thereby the wettability, is essential for satisfactory performance.…”

“…Adhering cell populations in the 3D mat network of Figure 2 are typically increased by plasma treatments (i) or (ii) by a factor of 5 or more compared with untreated (“control”) sample surfaces. [ 19,21 ]…”