Fat grafting based on 3D printed polyhydroxyalkanoate scaffolds

Autologous fat grafting holds significant promise for soft tissue repair and reconstruction. However, its clinical application faces challenges, including insufficient graft strength for optimal shaping and poor long-term retention rates, particularly in large-volume transplantation. Three-dimensional (3D)-printed biodegradable scaffolds offer a potential solution by mitigating graft ischemia and hypoxia, thereby improving retention, while offering temporary mechanical support before degradation. Polyhydroxyalkanoates (PHA) containing 3-hydroxybutyrate and 4-hydroxybutyrate monomers, a promising class of biomaterials in tissue engineering, were employed in this study to fabricate 3D-printed scaffolds for fat grafting. Their effects on graft retention were explored for underlying mechanisms. In vivo studies demonstrated that 3D-printed PHA scaffolds significantly enhanced fat graft retention by stimulating angiogenesis, promoting adipocyte viability, inducing macrophage polarization toward the M2 phenotype, attenuating oxidative stress, and optimizing mitochondrial functions. Additionally, the scaffolds further improved retention by facilitating beige adipogenesis or white adipose tissue browning. In vitro experiments confirmed the excellent biocompatibility of PHA, with its degradation product ‐3-hydroxybutyrate (3HB) exhibiting no cytotoxicity. Furthermore, 3HB enhanced the energy metabolism of adipose-derived stem cells (ADSCs) by reducing oxidative stress and improving mitochondrial function. This study provides solid evidence supporting the application of PHA scaffolds in adipose tissue engineering and proposes a novel strategy for soft tissue reconstruction and repair.