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.

摘要 美国每年有超过10万名女性因乳腺癌而接受乳房切除手术，导致乳房组织丢失。患者乳腺组织的关键特征之一是乳头乳晕复合体(NAC)，这一特征在重建过程中经常被忽视。NAC的重建或再生在临床上尚无可行的解决方案。这项工作的长期目标是开发一种个性化的、可生物吸收的NAC，为患者提供天然乳头突出的形状。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系统，这两种聚合物(1)定义了NAC的结构，(2)促进了组织向NAC内生长。NAC植入物最终会降解，在其位置上留下一个在大小、形状和质地上与原始组织相似的重建的NAC。为此，我们提出了三个具体目标。具体目标1将生物打印一个可行的和可翻译的新AC。我们将通过SolidWorks生成一系列NAC植入物设计，从而实现个性化植入物的快速开发。CAD设计将探索乳头投影高度、乳头直径、乳晕直径和NAC填充图案对植入物性能的影响，特别是对形状随时间保持的影响。NAC植入物将由可快速平移的生物材料制造。将评估物理和生物学特性(形状、力学、细胞种植效率、细胞存活/增殖、基质产生)，并将评估单个植入物组件的特性和降解。特异性目标2将建立生物印迹的NAC的体外培养系统。我们已经开发了一种3D打印生物反应器，专门用于生物打印的NAC的培养，因为由于其组织生物学(空气-水界面)和组织结构(非平面投影形状)，该结构提出了独特的培养挑战。NAC生物反应器将被制造并用于培养生物打印的构建物。将优化培养条件，包括培养基流量，以支持细胞增殖和功能(ECM生产)，同时保持NAC系统的形状。最后，Aim 3将对生物打印的NAC进行血管化。我们认为，临床上可翻译的生物打印植入物的成功策略是利用血管从周围宿主组织向NAC的生长。为此，我们将设计和构建一个层次化的NAC血管网络，该网络由打印的微血管和宿主组织引导的自组装微血管组成。在我们已建立的动物模型的基础上，我们将优化NAC的血管功能(架构、细胞密度)，以提供快速建立、足够的营养输送和血管功能的关键结果-同时保持NAC的结构和功能。这项拟议工作的结果将是能够产生个性化的乳头乳晕复合体，可以在丘状重建期间或以后植入。