Future work

Our work in this project has provided definitive data on the direct effect of Col 3 coated fibrous

scaffolds in promoting breast cancer cell apoptosis. Our next step would be to conduct in vitro

specificity tests to confirm that our methods are not promoting similar responses in non-

pathologic cells, although published and preliminary data from the Volk laboratory and others

suggest that this is extremely unlikely. It is possible that non-pathological cells differentially

express Col 3 receptors (ex. integrins), thereby effecting the fate of such cells, i.e. probably

limiting the pro-apoptotic effect of Col 3 on such cells. In addition, we will compare the effect

of Col 3- and Col 1-coated unaligned fibrous scaffolds on breast cancer cell apoptosis, to

determine if Col 3 coating remains superior in its ability to induce apoptosis in the context of an

unaligned scaffold. An important next step will be to shift focus to in vivo studies, where we

would be experimenting with fibrous scaffolds with an added sacrificial component. Research

by the Mauck lab has shown that composites containing the slow-degrading PCL and water-

73

mesh, by selectively removing the sacrificial component55_{. This enables for enhanced cell}

infiltration and improved matrix integration. This also leads to an increase in the tensile

properties of the engineered constructs (providing for a close imitation of the native ECM)55_{. In}

relation, we will also be conducting porosity analysis on our composite scaffolds to determine

the effect of porosity on cancer cell infiltration and apoptosis. Ultimately, we will assess if these

scaffolds promote apoptosis of microscopic residual disease in resection sites in vivo and if this

promotion of apoptosis would be able to prevent local recurrence and ultimately metastasis.

Based on previous research, we also predict these biomaterials will improve quality of healing

post-surgery. Future studies will directly test this hypothesis. Additional potential avenues of

research also include whether Col 3-based biomaterials (in other forms) would be prevent the

progression of benign cancer into more aggressive types.

The possibility that Col 3 biomaterials can eliminate microscopic disease and therefore limit

local recurrence and ultimately metastasis provides for an exciting avenue for the treatment of

breast cancer, particularly if able to replace more toxic therapies such as chemo- or radiation

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82 Appendix

MATLAB program for quantifying circular variance

function [VarF]=Circular(Fetal2)%To input variance values

Fetal2=(Fetal2.*pi./180).*2;%To convert sin and cos angle values for i=1:length(Fetal2)%specifying length of array

Cosi(i)=cos(Fetal2(i));%converting input angle into cos angle

Sini(i)=sin(Fetal2(i));converting input angle into sin angle end

SumCos=(sum(Cosi)).^2;%squaring the summation of cos angle SumSin=(sum(Sini)).^2;%squaring the summation of sin angle RsqF2=SumCos+SumSin; %adding cos and sin angled

RF=sqrt(RsqF2);

Rfv=RF/length(Fetal2); VarF=1-Rfv;

In document Effect of type lll collagen coating of electrospun scaffolds on breast cancer cell apoptosis (Page 96-106)