探讨聚己内酯（PCL）乳房形态支架用于组织工程乳房的构建的可能性。

通过熔融沉积3D打印制备形态仿生的PCL支架，测量其机械性能，并使用新西兰大白兔动物模型，皮下植入该PCL支架12周和18周后，利用核磁共振成像（MRI）观察支架内部新生组织分布情况，在组织学（HE、Masson及EVG染色）上评估支架内部的脂肪、纤维及血管的分布情况，并进一步使用qRT-PCR检测了12周时PCL支架内部组织的成脂相关基因（PPAR-γ、C/EBP-β、AP-2）、炎症相关基因TNF-α及巨噬细胞标记物F4-80的表达情况，同时使用凝胶渗透色谱法分析了PCL植入体内后平均分子量的变化。2组间均数比较采用独立样本t检验，多组间比较采用单因素方差分析，组间两两比较采用LSD-t检验，配对设计的均数比较采用配对t检验。

制备的PCL支架孔隙率为（85.30±1.12）%，压缩模量为（8.18±1.39）MPa，植入新西兰大白兔动物模型皮下12周后，MRI影像学显示脂肪组织已由支架周围向内部侵入，HE、Masson及EVG染色同样在该支架边缘观察到部分新生脂肪组织及血管，而支架内部则以疏松排列的纤维组织为主；与原生脂肪比较，12周PCL支架内组织的基因表达分析成脂相关基因C/EBPβ表达水平（2.32±0.28比1.00±0.02）升高，而巨噬细胞标记物F4/80表达（0.80±0.12比1.00±0.03）降低（P均< 0.01）；18周后，HE染色证实支架内部已充满脂肪组织。基因表达证实，与原生脂肪比较，支架内部组织C/EBP-β （3.30±0.63比1.00±0.02），PPAR-γ （1.81±0.71比0.99±0.02）及AP-2表达水平（1.38±0.16比1.01±0.01）升高（P均< 0.01）；而TNF-α（0.50±0.15比1.00±0.01）及F4/80表达水平（0.52±0.09比1.00±0.03）均降低（P均< 0.001）。而植入体内PCL支架的分子量（M_n）在18周内变化不大[（65.04±2.24）kDa比（64.20±4.09） kDa]。

PCL支架具有较好的生物相容性，可用于组织工程乳房的构建，该新西兰大白兔动物模型的建立有利于乳房组织工程的进一步临床转化。

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.