3D Bioprinted Nipple-Areolar Complex Implants

3D 生物打印乳头乳晕复合植入物

• 批准号: 10672784
• 负责人: John P Fisher
• 金额: $ 58.61万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672784
• 关键词: 3-Dimensional; 3D Print; Address; Air; Anatomy; Animal Model; Appearance; Architecture; Areola; Biocompatible Materials; Biological; Biology; Bioreactors; Blood Vessels; Cell Proliferation; Cell Survival; Cell physiology; Cells; Cellularity; Childhood; Clinical; Complex; Data; Development; Diameter; Discipline of obstetrics; Encapsulated; Extracellular Matrix; Goals; Granulation Tissue; Growth; Gynecologic; Height; Hybrids; Implant; In Vitro; Individual; Maintenance; Mammaplasty; Mammary Gland Parenchyma; Mastectomy; Mechanics; Natural regeneration; Nipples; Nutrient; Outcome; Patients; Pattern; Performance; Polymers; Porosity; Positioning Attribute; Printing; Procedures; Process; Production; Proliferating; Property; Reconstructive Surgical Procedures; Research; Shapes; Structure; Supporting Cell; System; Tattooing; Testing; Texture; Time; Tissue constructs; Tissues; United States; Vascularization; Water; Woman; Work; bioprinting; clinical translation; clinically relevant; design; healing; implant design; implantation; in vivo; malignant breast neoplasm; mechanical properties; neglect; neovascularization; psychological distress; reconstruction; satisfaction; scaffold; self assembly; subcutaneous; trait

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.

抽象的 由于乳腺癌，每年在美国有100,000多名女性接受乳房切除术，导致乳房组织的丧失。重建中经常被忽略的患者乳腺组织的关键特征之一是乳头酸乳液复合物（NAC）。 NAC重建或再生没有临床上可行的解决方案。这项工作的长期目标是开发一个个性化的生物吸收NAC，该NAC将为患者提供本地乳头投射的形状。为了实现这一目标，我们开发了一种由两种互补聚合物组成的混合生物材料植入物系统，该聚合物（1）定义了NAC的结构，（2）鼓励组织向内生长进入NAC。 NAC植入物最终将降解，将其放置在其大小，形状和质地上的原始组织相似的重建NAC。为此，我们建议三个具体的目标。特定的目标1将生物构成可行的可翻译NAC。我们将通过SOLIDWORKS生成NAC植入物设计组合，从而可以快速开发个性化植入物。 CAD设计将探讨乳头投影高度，乳头直径，乳晕直径和NAC填充物在植入物的特性上的影响，尤其是随着时间的推移保留形状。 NAC植入物将由快速翻译的生物材料制造。将评估物理和生物学特性（形状，力学，细胞播种效率，细胞活力/增殖，基质产生），并评估各个植入物的特性和降解。特定目标2将建立生物打印NAC的体外培养系统。我们已经开发了一个专门针对生物启动NAC培养的3D打印的生物反应器，因为该结构由于其组织生物学（空气水界面）和组织结构（非平面投影形状）引起了独特的培养挑战。 NAC生物反应器将被制造并用于培养生物打印构建体。包括培养基流量在内的培养条件将被优化，以支持细胞增殖和功能（ECM产生），同时保持NAC系统的形状。最后，AIM 3将使生物打印的NAC进行血管化。我们建议，可用于临床可翻译的生物打印植入物的成功策略将利用周围宿主组织和NAC的血管生长。为此，我们将设计和制造一个分层的NAC脉管系统，该网络由印刷的微脉管系统和由宿主组织指示的自组装微脉管系统组成。为了进一步发展我们既定的动物模型，我们将优化NAC的脉管系统（建筑，细胞），以提供快速建立，足够的营养递送和血管功能的关键结果 - 同时保持NAC的结构和功能。拟议的工作的结果将是能够产生个性化的乳头复合物，该复合物可以在土墩重建期间或以后植入。