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 美国每年有超过 100,000 名女性因乳腺癌而接受乳房切除手术，导致乳房组织损失。在重建过程中经常被忽视的患者乳房组织的关键特征之一是乳头乳晕复合体（NAC）。 NAC 重建或再生尚无临床可行的解决方案。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，我们开发了一种混合生物材料植入系统，由两种互补的聚合物组成，(1) 定义 NAC 的结构，(2) 促进组织向 NAC 内生长。 NAC 植入物最终会降解，在其位置留下重建的 NAC，其大小、形状和纹理与原始组织相似。为此，我们提出三个具体目标。具体目标 1 将生物打印出可行且可翻译的 NAC。我们将通过 Solidworks 生成 NAC 植入物设计组合，以便快速开发个性化植入物。 CAD 设计将探索乳头突出高度、乳头直径、乳晕直径和 NAC 填充图案对植入物性能的影响，特别是对随着时间的推移保持形状的影响。 NAC 植入物将由可快速翻译的生物材料制成。将评估物理和生物特性（形状、力学、细胞接种效率、细胞活力/增殖、基质产生），并将评估各个植入物组件的特性和降解。具体目标 2 将为生物打印 NAC 建立体外培养系统。我们开发了一种专门用于生物打印 NAC 培养的 3D 打印生物反应器，因为该结构因其组织生物学（空气-水界面）和组织结构（非平面投影形状）而带来独特的培养挑战。 NAC 生物反应器将被制造并用于培养生物打印的构建体。培养条件（包括培养基流速）将得到优化，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 将对生物打印的 NAC 进行血管化。我们建议临床可转化生物打印植入物的成功策略将利用周围宿主组织的血管向内生长并进入 NAC。为此，我们将设计和制造一个分层的 NAC 脉管系统网络，该网络由印刷的微脉管系统和由宿主组织引导的自组装微脉管系统组成。进一步完善我们已建立的动物模型，我们将优化 NAC 的脉管系统特征（结构、细胞结构），以实现快速建立、充足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。拟议工作的结果将是能够生产个性化的乳头乳晕复合体，可以在丘重建期间或以后植入。