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    Awarded Grants
    Assessment of Adipose Tissue Engineering to Restore the Postmastectomy Breast

    Scientific Abstract:
    Breast cancer is a debilitating disease with far reaching implications, impacting upon not only the physical, but also the psychological, and emotional well being of affected patients. Although tremendous scientific efforts have occurred in an effort to eradicate breast cancer, the incidence of breast cancer has continued to rise for the past two decades. Surgical intervention, either in the form of local or wide surgical resection (lumpectomy and mastectomy, respectively) is currently integral to the care for breast cancer, and is likely to remain a pivotal part of the treatment algorithm for a long time to come. Contemporary breast reconstruction modalities include breast implants and/or free tissue transfer (i.e., autologous donor tissue). Although autologous tissues are considered optimal for reconstruction, large vascularized grafts cause considerable donor deformity and morbidity, and liposuctioned grafts, although producing less deformity, simply does not work for large-volume defects. An alternative approach would be to harvest a small amount of fat (via a small, inconspicuous biopsy), grow the harvested fat cells to a sufficient volume and shape, add a blood supply, and affix the construct to the reconstructive site, where it would incorporate and persist, unchanged over time. The novel field of tissue engineering has the potential to restore a patient’s breast using such an approach. The ultimate goal of our research is to develop a clinically translatable tissue engineering strategy that permits a woman to regrow her own breast. We hypothesize that biodegradable and bioactive polymer scaffolds preseeded with autologous preadipocytes and placed in direct apposition to an artery-vein will result in the generation and persistence of de novo, vascularized adipose tissue within a porcine animal model. To address the hypothesis the following specific aims are proposed over a two-year period: 1. Fabricate clinically sized biodegradable and bioactive polymer scaffolds for implantation into a porcine animal model in a manner amenable to placement around an artery-vein. 2. Translate previous culturing procedures to culture autologous porcine preadipocytes and validate differentiation to mature adipocytes. 3. Demonstrate de novo adipogenesis within preadipocyte-seeded constructs implanted for up to 6 months in direct apposition to deep inferior epigastric vessels and optimize construct and surgical variables.

    Lay Abstract:
    Breast cancer is a debilitating disease with far reaching implications, impacting upon not only the physical, but also the psychological, and emotional well being of affected patients. Although tremendous scientific efforts have occurred in an effort to eradicate breast cancer, the incidence of breast cancer has continued to rise for the past two decades. Surgical intervention, either in the form of local or wide surgical resection (lumpectomy and mastectomy, respectively) is currently integral to the care for breast cancer, and is likely to remain a pivotal part of the treatment algorithm for a long time to come. Contemporary breast reconstruction modalities include breast implants and/or free tissue transfer (i.e., autologous donor tissue). Although autologous tissues are considered optimal for reconstruction, large vascularized grafts cause considerable donor deformity and morbidity, and liposuctioned grafts, although producing less deformity, simply does not work for large-volume defects. An alternative approach would be to harvest a small amount of fat (via a small, inconspicuous biopsy), grow the harvested fat cells to a sufficient volume and shape, add a blood supply, and affix the construct to the reconstructive site, where it would incorporate and persist, unchanged over time. The novel field of tissue engineering has the potential to restore a patient’s breast using such an approach. The ultimate goal of our research is to develop a clinically translatable tissue engineering strategy that permits a woman to regrow her own breast. To this end and based on our preliminary studies, we hypothesize that biodegradable and bioactive polymer scaffolds preseeded with fat cells and placed in direct contact with blood vessels will result in the generation and persistence of new, viable fat tissue. We will fabricate novel scaffolds for fat cells to grow on and demonstrate successful fat formation and viability in a pig model. This innovative, multidisciplinary proposal couples the disparate fields of bioengineering, clinical and surgical science, and molecular and cell biology. Successful completion of these aims will represent a tremendous leap forward in adipose tissue engineering and will advance the clinical translation of adipose tissue engineering so that breast cancer patients’ outcomes and quality of life can be improved.