Additive manufactured macroporous chambers facilitate large volume soft tissue regeneration from adipose-derived extracellular matrix

Breast tissue engineering is a promising alternative intervention for breast reconstruction. Due to their low immunogenicity and well-preserved adipogenic microenvironment, decellularized adipose tissue (DAT) can potentially regenerate adipose tissue in vivo. However, the volume of adipose tissue regenerated from DAT can hardly satisfy the demand for breast reconstruction. Tissue engineering chamber (TEC) is an effective technique for generation of large adipose tissue volumes. However, TEC applications necessitate reoperation to remove non-degradable plastic chambers and harvest autologous tissue flaps, which prolongs the operation time and causes potential damage to donor sites. We improved the TEC strategy by combining bioresorbable polycaprolactone (PCL) chambers and decellularized adipose tissues (DAT). A miniaturized porous PCL chamber was fabricated based on scaling differences between human and rabbit chests, and basic fibroblast growth factor (bFGF)-loaded DAT successfully prepared. In rabbit models, a highly vascularized adipose tissue that nearly filled up the PCL chamber (5 mL) was generated de novo from 0.5 mL bFGF-loaded DAT. The newly formed tissue had significantly high expressions of adipogenic genes, compared to the endogenous adipose tissue. The concept described here can be exploited for breast tissue engineering. STATEMENT OF SIGNIFICANCE: Decellularized adipose tissue (DAT), which provides infiltrated cells adipogenic microenvironment, can potentially regenerate adipose tissue in vivo. Nevertheless, the volume of regenerated adipose tissue is insufficient to repair large sized tissue defect. Tissue engineering chamber (TEC) could provide a protective space for in situ regeneration of large volume tissue. Herein, a new strategy by combining biodegradable polycaprolactone chambers and basic fibroblast growth factor-loaded decellularized adipose tissue is proposed. In rabbit model, newly formed adipose tissue regenerated from DAT successfully filled the dome shaped chamber with ten folds higher volume than DAT, which is proportionally similar to women breast. This work highlighted the importance of adipogenic microenvironment and protective space for adipose tissue regeneration.