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Sci Transl Med. 2015 Jan 28;7(272):272ra11. doi: 10.1126/scitranslmed.aaa1616.

Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia.

Author information

1
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
2
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Industrial Engineering, Institut Quimic de Sarrià, Universitat Ramon Llull, Barcelona 08017, Spain.
3
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Ort Braude College, Karmiel 21982, Israel.
4
Concord Biomedical Sciences and Emerging Technologies, Lexington, MA 02421, USA.
5
Division of Comparative Medicine, MIT, Cambridge, MA 02139, USA.
6
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
7
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. nartzi@mit.edu.

Abstract

A "one material fits all" mindset ignores profound differences in target tissues that affect their responses and reactivity. Yet little attention has been paid to the role of diseased tissue on material performance, biocompatibility, and healing capacity. We assessed material-tissue interactions with a prototypical adhesive material based on dendrimer/dextran and colon as a model tissue platform. Adhesive materials have high sensitivity to changes in their environment and can be exploited to probe and quantify the influence of even subtle modifications in tissue architecture and biology. We studied inflammatory colitis and colon cancer and found not only a difference in adhesion related to surface chemical interactions but also the existence of a complex interplay that determined the overall dendrimer/dextran biomaterial compatibility. Compatibility was contextual, not simply a constitutive property of the material, and was related to the extent and nature of immune cells in the diseased environment present before material implantation. We then showed how to use information about local alterations of the tissue microenvironment to assess disease severity. This in turn guided us to an optimal dendrimer/dextran formulation choice using a predictive model based on clinically relevant conditions.

PMID:
25632035
PMCID:
PMC4627493
DOI:
10.1126/scitranslmed.aaa1616
[Indexed for MEDLINE]
Free PMC Article

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