I-Corps: A Tissue-engineered Nipple-Areolar Complex

目前，美国每年有超过23万名女性被诊断出患有乳腺癌；每年大约有18万女性因癌症接受乳房切除术。这些患者，大多数是女性，有几种方法可以选择乳头-乳晕复合体（NAC）重建。这些选择最常见的包括整形和重建外科医生，通过手术从胸部或身体其他部位（如大腿或腋下）的皮肤中创造一个看起来像乳头的结构；或者可以在乳房重建阶段后进行NAC图像的纹身；或者结合纹身或手术方法。对于这些NAC重建，结果取决于许多因素：手术技巧、皮肤厚度、重建乳头状结构的血液供应、纹身技巧、纹身褪色等。作为目前重建NAC的标准方法的替代方案，I-Corps团队开发了一种移植物，可以使患者的NAC再生。作为这个概念的总体目标，一个现成的NAC移植物将提供给整形和重建外科医生。在乳房重建阶段，在乳房切除术后，外科医生将这些NAC移植物中的一个植入到患者重建的乳房上。然后，患者的身体将使用这种NAC移植物作为建筑框架来再生自己的NAC。类似的材料已经在手术中使用了30多年；通过对这些材料及其加工过程进行重新成像，我们可以将成熟的过程和重建方法应用于接受乳房切除术的妇女的NACs再生。在近18万例乳房切除术中，需要一种可复制的现成移植物用于乳头-乳晕复合体（NAC）重建。美国有超过280万乳腺癌幸存者，其中许多人接受了重建手术。大约36%的早期诊断患者和60%的晚期诊断患者接受乳房切除术。此外，乳房切除术后立即乳房重建也变得越来越普遍，从1998年的20.8%显著增加到2008年的37.8%。这种增加的趋势并不令人惊讶，因为有证据表明NAC重建会影响接受乳房切除术的女性患者的心理健康。证据还表明，如果在乳房切除术过程中可以保留乳头，或者如果不能选择保留乳头的乳房切除术，可以进行乳头重建，那么女性更愿意接受乳房切除术。目前NAC重建的策略仅限于手术技术，即从现有的局部组织、继发部位移植、3D纹身或手术重建与纹身相结合来创建NAC样结构。生成组织工程的、具有生物相容性的NAC移植物，用于替代手术创建的NAC结构，是乳房切除术后NAC重建的一种很有前途的方法。到目前为止，还没有针对NAC结构再生的组织工程策略。通过分离生物源性的富含胶原的脱细胞NAC支架，维持NAC原有的微观和宏观结构成分。整个项目的目标是为整形和重建外科医生提供现成的NAC移植物，可以在乳房重建期间将其移植到患者身上，允许患者的皮肤细胞重新填充支架，从而再生患者的NAC。

Currently, there are more than 230,000 women diagnosed with breast cancer every year in the United States; and there are approximately 180,000 female mastectomies that occur each year due to cancer. These patients, mostly women, have several options in the way they could have their nipple-areolar complex (NAC) reconstructed. These options most commonly include the plastic and reconstructive surgeons, surgically creating a structure that looks like a nipple, out of skin from the chest area or from other part of the body, such as the thigh or under the arm; or a tattoo of a image of NAC can be done after the reconstructions phase of the breast; or a combination of tattoo or surgical methods. For these NAC reconstructions, the outcome is contingent on many factors: surgical skill, skin thickness, blood supply to the reconstructed nipple-like structure, tattooing skill, fading of tattoo, etc. As an alternative to these current standard methods to reconstruct the NAC this I-Corps team has have developed a graft that would regrow the patient's NACs. As an overall goal to this concept, an off-the-shelf ready NAC graft would be made available to the plastic and reconstructive surgeons. During the breast reconstruction phase, after a mastectomy, the surgeon would then engraft one of these NAC grafts in position onto the patient's reconstructed breast. The patient's body would then use this NAC graft as a building frame to regenerate their own NAC. Materials similar to these have been used in surgeries for more than 30 years; by reimaging these materials and their processing, it has allowed us to apply well-established processes and reconstruction methods to the regeneration of NACs for women who have undergone mastectomies.There exists a need for a reproducible off-the-shelf ready graft for Nipple-Areolar Complex (NAC) reconstruction, for the approximately 180,000 mastectomies that. There are more than 2.8 million breast cancer survivors in the United States, many of who have undergone reconstructive surgery. Approximately 36% of patients with early stage diagnoses and 60% of patients with late stage diagnoses undergo mastectomies. Moreover, immediate breast reconstruction following mastectomies has become more common, significantly increasing at from 20.8% in 1998 to 37.8% in 2008. This increasing trend is not surprising as there is evidence to suggest that NAC reconstruction affects psychological wellbeing of female patients who have undergone mastectomies. Evidence also suggests that woman are more comfortable with getting a mastectomy if the nipple can be spared during the mastectomy procedure, or if nipple reconstruction is possible if a nipple-sparing mastectomy is not an option. Current strategies for NAC reconstruction are limited to surgical techniques that create a NAC-like structure from existing local tissue, secondary site grafting, or 3D tattooing, or a combination of surgical reconstruction with tattooing. Generating a tissue engineered, biocompatible NAC graft for use in place of surgically created NAC structures is a promising approach to NAC reconstruction following mastectomies. To date, no tissue engineering strategies have been targeted towards the regeneration of the NAC structure. By isolating a biological-derived collagen-rich acellular NAC scaffold, the NAC native micro and macro structural components are maintained. The goal of this overall project is to provide the plastic and reconstructive surgeons an off-the-shelf ready NAC graft, that could be onlay grafted onto the patient during breast reconstruction, allowing for patient resident skin-cells to repopulate the scaffold, thereby regenerating the patients' NAC.