Acellular nipple scaffold development, characterization, and preliminary biocompatibility assessment in a swine model.

BACKGROUND
The gold standard in nipple reconstruction remains the autologous skin flap. Unfortunately the results are not satisfying with up to 75% loss of nipple projection over time.1-8 Existing studies investigated the use of primates as a source of implants.9,10 We hypothesized that porcine nipple can serve as a perfect shape-supporting implant due to functional similarities to human nipple.11,12 Our group developed a decellularization protocol to obtain an acellular nipple scaffold (ANS) for nipple reconstruction.


METHODS
Tissue samples were collected from 8 disease-free female Yorkshire pigs (60-70 kg) and then decellularized. The decellularization efficiency and extracellular matrix (ECM) characterization was performed histologically and quantitatively (DNA, total collagen, elastin, and glycosaminoglycan content). In vitro and in vivo biocompatibility was determined by human dermal fibroblast culture and subcutaneous implantation of six ANS in a single Yorkshire pig (60-70 kg) respectively. Inflammation and adverse events were monitored daily based on local clinical signs.


RESULTS
We showed that all cellular structures and 96% of DNA (321.7±57.6 vs. 11.7±10.9 ng DNA/mg wet tissue, in native and ANS, respectively, p<0.001) can be successfully removed. However, this was associated with a decrease in collagen (89.0±11.4 and 58.8±9.6 μg collagen/mg (p<0.001)) and elastin (14.2±1.6 and 7.9±2.4 μg elastin/mg (p<0.05)) and increase in GAG content (5.0±0.7 and 6.0 ± 0.8 ng/mg (p<0.05)). ANS can support continuous cell growth in vitro and during preliminary biocompatibility tests in vivo.


CONCLUSIONS
This is a preliminary report a novel promising ANS for nipple reconstruction, but more research is needed to validate results.