Wednesday, December 4, 2024
12/4/2024
ABSTRACT Over 100,000 women in the United States undergo mastectomy procedures each year due to breast cancer, resulting in loss of breast tissue. One of the key traits of a patient's breast tissue that is often neglected in reconstruction is the nipple areolar complex (NAC). There is no clinically viable solution for NAC reconstruction or regeneration. The long-term goal of this work is to develop a personalized, bioresorbable NAC that will provide patients with the shape of a native nipple projection. To pursue this goal, we have developed a hybrid biomaterial implant system consisting of two complementary polymers that (1) define the architecture of the NAC and (2) encourages tissue ingrowth into the NAC. The NAC implant will eventually degrade, leaving in its place a reconstructed NAC that is similar to the original tissue in size, shape, and texture. To this end, we suggest three specific aims. Specific Aim 1 will bioprint a viable and translatable NAC. We will generate a portfolio of NAC implant designs via Solidworks, allowing for rapid development of personalized implants. CAD designs will explore the impact of nipple projection height, nipple diameter, areola diameter, and NAC infill patterning upon the implant's properties, and particularly on the retention of shape over time. NAC implants will be fabricated from rapidly translatable biomaterials. Physical and biological properties {shape, mechanics, cell seeding efficiency, cell viability/ proliferation, matrix production) will be assessed, and individual implant component properties and degradation will be evaluated. Specific Aim 2 will establish an in vitro culture system for a bioprinted NAC. We have developed a 3D printed bioreactor specifically for the culture of a bioprinted NAC, as the construct presents unique culture challenges due to its tissue biology (air-water interface) and tissue architecture (non-planar projection shape). NAC bioreactors will be fabricated and employed to culture the bioprinted constructs. Culture conditions, including media flow rate, will be optimized to support cell proliferation and function (ECM production), while maintaining shape of the NAC system. Finally, Aim 3 will vascularize a bioprinted NAC. We suggest that the successful strategy for a clinically translatable bioprinted implant will utilize vascular ingrowth from the surrounding host tissue and into the NAC. To this end, we will design and fabricate a hierarchical NAC vasculature network consisting of a printed microvasculature and a self-assembled microvasculature directed by host tissue. Furthering our established animal model, we will optimize the NAC's vasculature features (architecture, cellularity) to deliver the critical outcomes of rapid establishment, sufficient nutrient delivery, and vascular functionality- while maintaining the NAC's structure and function. The result of the proposed work will be the ability to produce a personalized nipple areolar complex that can be implanted during mound reconstruction or at a later date.
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