Adipogenesis of bioabsorbable implants under irradiation in a rodent model

Abstract

Background: Breast cancer is the most common cancer among women. Partial mastectomy is an alternative to mastectomy in early-stage breast cancer to restore a poor quality of life (QOL). However, the aesthetic satisfaction with this procedure is inadequate. The standard methods for breast reconstruction have certain limitations. We developed bioabsorbable implants consisting of an outer mesh composed of poly L-lactic acid (PLLA) and an inner component filled with a collagen sponge (CS). These implants were designed to promote and sustain adipogenesis in vivo, without the addition of exogenous cells or growth factors. In this study, we used PLLA mesh implants to investigate the effects of irradiation on fat formation, which is important in partial mastectomy.

Methods: The implants were inserted into both the inguinal regions of the rats. One month after the implantation, a dose of 13 Gy was delivered to the left-side implants. We compared adipose tissue formation in the non-irradiated and irradiated groups at 6 and 12 months after irradiation.

Results: Irradiation of implants did not lead to malignant tumor formation. The newly formed tissues and adipose tissue were not significantly different between the two groups at 6 and 12 months after irradiation.

Conclusions: PLLA mesh implants containing CS are desirable bioabsorbable implants that can be replaced with autologous adipose tissue after in vivo implantation under irradiation. These implants serve as an effective material for partial mastectomy and have the potential to improve the QOL of patients after mastectomy.

Keywords: Adipogenesis; Bioabsorbable; Breast cancer; Irradiation; Partial mastectomy; Poly-L-lactic acid.

Fig. 1

(a) Gross appearance of the implants. The implant consisted of a poly L-lactic acid mesh with a collagen sponge. The dashed white arrow indicates the greatest diameter of the short axis of the implant, and the solid white arrow indicates the greatest length of the long axis of the implant. Scale bar = 1 cm. (b) Histological assessment of the newly formed tissue in the inguinal region. The area enclosed by the red dotted line represents the shape of the implant. The implant is divided into four equal parts along the long axis, as indicated by the straight black line. Scale bar = 1 cm. (c) Evaluation of the area of newly formed adipose tissue inside implants. The red dotted line shows the area of newly formed tissue, and the yellow dotted line shows the area of newly formed adipose tissue inside the implants.

Fig. 2

The lead shield under irradiation. (a) Front view; (b) caudal views.

Fig. 3

Gross appearance of all newly formed tissues. The gross appearance of the irradiated group at (a) 6 and (b) 12 months after irradiation. The gross appearance of the non-radiated group at (c) 6 and (d) 12 months after irradiation. Scale bar = 1 cm.

Fig. 4

Weight and volume of all newly formed tissues. (a) Time course of the weight of all newly formed tissues. (b) Time course of the volume of all newly formed tissues. No significant difference was observed between the two groups at 6 or 12 months after irradiation. Data are presented as mean ± standard deviation. ∗p < 0.01 versus at the 6 months, ^†p < 0.01 versus at the 6 months. 〇 = non-irradiated group;, △ = irradiated group.

Fig. 5

Light micrographs of the hematoxylin- and eosin-stained sections of the newly formed tissue. Light micrographs of the irradiated group at (a) 6 and (b) 12 months after irradiation. Light micrographs of the non-radiated group at (c) 6 and (d) 12 months after irradiation. The PLLA threads were confirmed up to 12 months after irradiation. Scale bar = 1 mm.

Fig. 6

Light micrographs of the Azan-stained sections of the newly formed tissues. Light micrographs of the irradiated group at (a) 6 and (b) 12 months after irradiation. Light micrographs of the non-radiated group at (c) 6 and (d) 12 months after irradiation. Collagen formation was confirmed at the center of the implants at 12 months after irradiation in both the groups. Scale bar = 1 mm.

Fig. 7

Light micrographs of the perilipin-stained sections of the newly formed tissue. Light micrographs of the irradiated group at (a) 6 and (b) 12 months after irradiation. Light micrographs of the non-radiated group at (c) 6 and (d) 12 months after irradiation. Adipose tissue expanded from the perimeter of the implant after irradiation. Scale bar = 1 mm.

Fig. 8

Light micrographs of the CD31-stained sections of the newly formed tissues. Light micrographs of the irradiated group at (a) 6 and (b) 12 months after irradiation. Light micrographs of the non-radiated group at (c) 6 and (d) 12 months after irradiation. The formation of blood vessels inside the implants was similar in both the groups. Scale bar = 1 mm.

Fig. 9

Evaluation of the area of newly formed and adipose tissues, as well as the percentage of adipose tissue inside the implants. (a) The area of newly formed tissue inside the implant. (b) The area of newly formed adipose tissue inside the implant. (c) Percentage of adipose tissue in the newly formed tissue inside the implant. No significant differences were observed between the irradiated and non-irradiated groups in the areas of newly formed and adipose tissue and the percentage of adipose tissue at any point. Data are presented as mean ± standard deviation. ∗p < 0.05 versus at 6 months, ^†p < 0.01 versus at 6 months. 〇 = non-irradiated group;, △ = irradiated group.

Fig. S1

Light micrographs of the hematoxylin- and eosin-stained sections of the newly formed tissue at 1 month after implantation. The formation of adipose tissue was not confirmed. Scale bar = 1 mm.