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According to estimations of the Global Cancer Observatory, over 2.2 million women were diagnosed with breast cancer in 2020, worldwide. [1] While most often requiring surgical removal of the affected breast tissue, breast reconstruction following mastectomy remains a challenge. [2] Conventional reconstruction techniques, using synthetic prostheses or autologous tissue, are accompanied with risks and complications such as infection, prosthesis rupture, capsular contracture, donor site morbidity, uncontrollable resorption rates and the need for reinterventions. [3,4,5] Therefore, a strong research focus is directed towards regenerative adipose tissue engineering, shifting reconstruction strategies from tissue replacement to autologous tissue regeneration.
In the present work, a novel approach is introduced to enable minimally invasive, patient-specific, aesthetically elegant breast reconstruction. Shape memory copolymers based on aliphatic polyesters were synthesized and functionalized into diacrylate and hexaacrylate end-capped urethane-based polymers (AUPs) to enable chemical crosslinking. The materials were tuned in order to achieve a glass transition temperature below body temperature. The AUPs were characterized physico-chemically by proton nuclear magnetic resonance (1H-NMR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
Subsequently, a photo-sensitive resin was developed based on the synthesized AUPs, rendering them suitable for digital light processing (DLP). By varying the molar mass of the polymer, the acrylate content of the AUPs and the concentration of photoinitiator and photoabsorber, the resin was optimized towards efficient photo-crosslinking. Furthermore, the gel fraction and swelling ratio were determined. Once optimized, the photo-sensitive resin was processed into porous scaffolds by means of DLP. The morphology of the scaffolds was investigated using optical microscopy and scanning electron microscopy. Suitable pore sizes were obtained for diacrylate AUPs, whereas for hexaacrylate AUPs further optimization is required.
Preliminary in vitro biocompatibility assays using adipose-derived stem cells were performed to assure the absence of cytotoxic components. The cytotoxicity was tested through an indirect assay in which the crosslinked materials were submerged during 24h, 72h and 7 days in culture media. The culture media, containing any leached components, was placed on top of the seeded cells in order to assess biocompatibility through a live/dead staining and MTS assay.
Finally, future experiments include (accelerated) degradation assays as well as mechanical characterization of the 3D printed scaffolds. Additionally, the shape memory properties will be investigated, as these will enable a shift in shape from a temporary reduced size into a permanent large, patient-specific volume upon implantation in the body, assuring minimally invasive surgery.
As a result, the developed porous shape memory scaffolds can be considered promising candidates towards minimally invasive, patient-specific adipose tissue engineering.
[1] International Agency for Research on Cancer 2021. GLOBOCAN 2020
[2] S. Winocour et al., “Hypoplastic breast anomalies in the female adolescent breast,” Semin. Plast. Surg., vol.27, no.1, pp.42–48, 2013.
[3] J. Regan et al., Breast Reconstruction. StatPearls Publishing LLC.
[4] A. Homsy, et al., “Breast Reconstruction: A Century of Controversies and Progress,” Ann. Plast. Surg., vol.80, no.4, pp.457–463, 2018.
[5] I. Van Nieuwenhove et al., “Soft tissue fillers for adipose tissue regeneration: From hydrogel development toward clinical applications,” Acta Biomater., vol.63, pp.37–49, 2017.
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