Development of injectable solvent-free tissue-mimetic platform for breast reconstructive surgery

Abstract Proposed is the development of a novel injectable material platform for breast reconstruction capable of time- controlled in-body curing, precisely mimicking the viscoelastic mechanics of surrounding tissue. This advanced solvent-, catalyst, and eventually reaction-free approach prevents leaching and enables minimally invasive surgery, improving the biocompatibility profile that overcomes the long-term health risks of currently marketed products. The focus on breast reconstruction is inspired by the alarming numbers of American women affected by breast cancer (1 in 8), with many undergoing lumpectomy or mastectomy. The significant quality of life (QOL) reduction in the aftermath of cancer survival can be addressed by breast reconstruction, as underscored by the Women’s Health and Cancer Rights Act of 1988 and President’s Executive Order on Advancing Women’s Health Research and Innovation from 03/18/24, which enforces insurance coverage of all reconstruction stages. Current implant options are mainly bifurcated into silicone gel- and saline-based devices. However, customers choose between silicone gel’s enhanced mechanical performance yet significant safety concerns or saline’s safer yet unnatural feel and disfigurement. Currently, all implant strategies demand substantial improvement due to a lack of tissue-like mechanics, uncontrolled leaching, capsular contracture (affecting 25%), and rupture (affecting 35%), entailing additional invasive explantation surgery for as high as 70% of all patients after 10 years. The proposed design-by-architecture platform will directly address the current implant shortcomings by merging 1) solvent-free, 2) minimally invasive, 3) cured within tailored time without using a catalyst, 4) leachable-free, and 5) tissue-mimetic mechanics, thus breaking the unsafe (status quo) aspects of breast reconstructive surgery. Preliminary data indicates these solvent- and leachable-free materials provide unprecedented biocompatibility, resilience, and longevity by remaining mechanically invariant over time, in contrast to FDA-approved technologies identified as not lifetime devices. As advised by clinicians, curing time is adjusted to 1-4 hours to allow continuous injection while avoiding disfigurement. A 9-month in vivo implantation study supports the biological safety of the proposed materials and curing procedures. We will advance breast reconstruction technology by optimizing its formulations, curing chemistry, and biocompatibility profile. Specific Aims include: 1) Conceptualization of network designs for efficient implantation; 2) Optimization of catalyst-free controlled crosslinking schemes for variable curing rate; 3) Replicating breast tissue mechanics; and 4) Biological evaluation of materials and curing protocols. The proposed technology will not only advance breast reconstruction but, given adjustable curing times and mechanical tunability, it enables translation into other types of reconstruction applications such as HIV-associated lipoatrophy of the face, buttocks, burns, tumor removal, and bodily injuries.