Innovative regenerative strategy for reconstructing breast defect: Gas-foamed gelatin methacryloyl scaffolds combined with human adipose-derived stem cell spheroids

The construction of vascularized tissue-engineered adipose tissue offers a promising alternative for breast defect repairs. However, the lack of a vascularized environment and inefficient adipose tissue differentiation hinder its application. Herein, an adipose regeneration strategy is proposed that integrates an innovative gas-foamed method (soil) and three-dimensional (3D) cell spheroids (seeds). The soil is optimized using a combination of gas-foaming and light-cured technology to generate foamed gelatin methacryloyl (f-GelMA), which provides a new strategy for the preparation of nontoxic porous hydrogels that significantly enhances the vascularization of the regenerated tissue. Seed cells were optimized to promote adipogenesis by replacing 2D monolayer adipose-derived stem cells (m-ADSC) with 3D ADSC spheroids (s-ADSC). The culture model based on f-GelMA and s-ADSC effectively promotes cell survival, migration, and adipogenic differentiation in vitro and significantly promotes the regeneration of vascularized adipose tissue in vivo. This study provides a solution for the regeneration of vascularized adipose tissue and establishes a general research model for the reconstruction of breast defects.