To explore the potential of polycaprolactone (PCL) breast-shaped scaffolds for the construction of tissue-engineered breasts and to investigate its biocompatibility and potential adipogenic ability via histological analysis and real-time quantitative polymerase chain reaction (qRT-PCR) .

The biomimetic PCL scaffold was prepared by fused deposition modeling and its mechanical properties were measured. PCL scaffolds were implanted subcutaneously using New Zealand rabbits. After 12 and 18 weeks, the distribution of newly-formed tissue inside the scaffold was observed using magnetic resonance imaging (MRI) and the distribution of fat, fibers and blood vessels inside the scaffold was assessed via histology (HE, Masson and EVG staining) . The expression of adipogenic genes (PPAR-γ, C/EBP-β, AP-2) , inflammation-related gene TNF-α and macrophage marker F4-80 in the tissues inside the PCL scaffold was further examined by qRT-PCR at 12 and 18 weeks. Changes of the mean molecular weight of PCL scaffold after implantation were also analyzed by gel permeation chromatography. Means between the 2 groups were compared using the independent samples t-test, one-way ANOVA for comparisons between multiple groups, LSD-test for two-way comparisons between groups, and paired t-test for comparison of means in a paired design.

PCL scaffold had a porosity of (85.30±1.12) % and a compression modulus of (8.18±1.39) MPa. MRI imaging showed that adipose tissue had invaded into the scaffold after 12 weeks. Compared with native adipose tissue, gene expression analysis of the tissue inside PCL scaffolds at 12 weeks showed an increase in the expression of the adipogenic gene C/EBP β (2.32±0.28 vs 1.00±0.02) and a decrease in the expression of the macrophage marker F4/80 (0.80±0.12 vs 1.00±0.03) (both P < 0.01) . After 18 weeks, HE staining confirmed that the scaffold was filled with adipose tissue. Gene expression confirmed increased expression of C/EBP-β (3.30±0.63 vs 1.00±0.02) , PPAR-γ (1.81±0.71 vs 0.99±0.02) and AP-2 expression levels (1.38±0.16 vs 1.01±0.01) compared to native adipose (all P < 0.01) ; whereas expression of TNF-α (0.50±0.15 vs 1.00±0.01) and F4/80 expression levels (0.52±0.09 vs 1.00±0.03) were reduced (both P < 0.001) . The molecular weight (M_n) of implanted PCL scaffolds in vivo did not change significantly over 18 weeks [ (65.04±2.24) kDa compared to (64.20±4.09) kDa].

These results showed scaffolds printed with PCL were capable and superior for breast tissue engineering because of their optimal mechanical property as well as biocompatibility. The establishment of the rabbit model was conducive to the further clinical transformation of breast tissue engineering.