ReConstruct: Vascularized Tissue for Breast Reconstruction and Augmentation

The Problem

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Breast cancer, the most common cancer worldwide, affects nearly 15% of all women. Most of these women undergo some kind of mastectomy to treat their cancer, and 40% choose to have breast reconstruction surgery. However, all currently available reconstruction options come with significant health risks. Artificial implants, whether filled with silicone or saline, require frequent safety monitor and must be replaced within 10 to 15 years. In addition, many of those implants are now restricted by the FDA because they are linked to other types of cancers.

Beyond breast reconstruction, artificial implants are widely used for breast augmentation, the second most common cosmetic surgery globally, with more than 2.1 million procedures performed each year. Patients undergoing breast augmentation face similar complications and health risks from artificial implants.

Autologous tissue flaps, in which a surgeon takes tissue, with intact blood vessels, from another part of a patient’s body and uses it to reconstruct the breast, are considered a more “natural” approach. But not all women have enough tissue for this procedure, and over 50% of patients experience complications at the tissue extraction site that can lead to additional hospitalizations and surgeries. Hence, there is a large, unmet clinical need for breast reconstruction options that are safe and robust and permanent solutions.

Our Solution

Scientists at the Wyss Institute have created an approach to creating living tissue implants from a patient’s own cells for breast reconstruction. The team combines three tissue engineering techniques: extracting a patient’s cells to create dense adipose (fat) tissue composed of personalized pre-assembled organ building blocks (OBBs), patterning a network of interconnected channels that template blood vessels within the tissue, and incorporating suturable cuffs that ensure that the implanted tissue has immediate and sufficient access to the patient’s own vascular network.

The adipose tissue engineering approach uses a novel bioprinting method known as sacrificial writing in functional tissue (SWIFT), which involves creating a dense cellular tissue matrix composed of OBBs, and uses a gelatin-based ink to “print” interconnected channels through the matrix. The ink is then melted and washed away, leaving a network of open vessels through which blood can be perfused to keep the tissue alive.

Product Journey

ReConstruct began as a collaboration between Wyss Faculty members Jennifer Lewis, Sc.D. and Chris Chen, M.D., Ph.D., both leaders of the Institute’s 3D Organ Engineering Initiative. Luba Perry, PhD., a member of the Wyss Advanced Technology Team in the Initiative since 2018, was tapped to lead the project given her expertise in in vivo validation and animal work. In this role, she has worked in close collaboration with Sebastien Uzel, Ph.D., co-inventor of the biomanufacturing platform used to create these tissues. Before joining the Wyss Institute, Luba was part of a startup team that developed an autologous biosynthetic vascular graft for hemodialysis, validated it in animal-study validation, and obtained IND-approval from the FDA to test it in a phase-I clinical study. The emerging ReConstruct team uses world-leading expertise in vascular engineering, 3D bioprinting, and microsurgery to fabricate the living tissue implants, and validate them for therapeutic use.

In 2020, before focusing on breast reconstruction and augmentation, the team was selected for Validation Project support to fabricate vascularized adipose tissues, on a large scale, that could be surgically connected to recipients’ blood vessels to allow immediate and long-lasting perfusion. Meeting with key opinion leaders and clinicians highlighted to the team that, although vascularized adipose tissues would be extremely valuable for multiple tissue reconstruction applications, their focus should be on addressing the unmet need for safe, long-term breast reconstruction and augmentation treatments.

In 2022, the team began collaborating with Dr. Samuel Lin, an Associate Professor of Surgery at Harvard Medical School and an expert in breast reconstruction to ensure that the technology is aligned with surgical procedures and needs.

Over the course of the ReConstruct project, the team steadily advanced their capabilities to create perfusable vascularized adipose tissue using donor cells and SWIFT technology, and invented a new suturable cuff to address a significant challenge in tissue implantation: ensuring an immediate and substantial blood supply from the patient’s bloodstream to the newly implanted tissue for prompt oxygen and nutrient. To support the in vivo validation of the engineered adipose tissue, they also developed a comprehensive suite of microsurgery protocols, and in a series of in vivo experiments, successfully showed that the implanted adipose tissues remain viable and well-perfused with host blood for several days after implantation.

Impact

In January 2023, ReConstruct was named an Institute Project in recognition of its significant potential for commercial success and positive impact on the lives of patients. With this additional funding, the team expanded and conducted final POC studies in rodents. The ReConstruct team plans to launch a startup as the most effective way to bring a safe breast reconstruction and augmentation option to patients in need, and in the long-term future will explore their platform’s ability to fabricate personalized fat tissues for other soft tissue reconstructions and to treat metabolic disorders like diabetes and obesity.

The team is currently seeking potential investors, partners, and collaborators who are interested in helping to commercialize this technology.