Porous Architecture and Pressure-Induced Latent Injury: New Insights into Large-Volume Fat Grafting

Large-volume autologous fat grafting for aesthetic augmentation is often complicated by cysts and fibrosis, suggesting that its survival mechanisms differ from those of small-volume grafts.

To investigate the survival biology of large-volume fat grafts and evaluate the effects of mechanical pressure on tissue structure, viability, and long-term graft outcome.

A 3-dimensional in vitro model using human adipose tissue in a scaffold was established. Constructs were cultured under 0, 6 or 12 mmHg of pressure to assess structural integrity, solute permeability, cell viability and molecular changes. The viable outer layer was then transplanted into nude mice to evaluate volume retention, necrosis and fibrosis.

In vitro, a porous interstitial network supported tissue survival to a depth of approximately 8 mm. Pressure dose-dependently disrupted this network, reducing solute permeability from 76.4% to 21.3% and impairing viability. Pressure also induced a form of "latent injury," consistent with YAP-related mechanotransductive signaling, lineage-related molecular changes and metabolic stress. In vivo, although gross volume retention was similar among groups, pressure-conditioned grafts developed marked necrosis, with fibrosis increasing from 22.1% in controls to 53.3% in the 12 mmHg group at 8 weeks.

Large-volume fat graft survival depends in part on the integrity of a pressure-sensitive porous network. Mechanical pressure may induce a clinically relevant "latent injury," consistent with molecular changes observed in vitro, which may contribute to later fibrosis. Minimizing mechanical stress during harvest, processing, handling and implantation may help preserve graft integrity and improve long-term outcomes.