TY - JOUR
T1 - Acellular Nipple Scaffold Development, Characterization, and Preliminary Biocompatibility Assessment in a Swine Model
AU - Oganesyan, Ruben V.
AU - Lellouch, Alexandre G.
AU - Acun, Aylin
AU - Lupon, Elise
AU - Taveau, Corentin B.
AU - Burlage, Laura C.
AU - Lantieri, Laurent A.
AU - Randolph, Mark A.
AU - Cetrulo, Curtis L.
AU - Uygun, Basak E.
N1 - Funding Information: This work was funded by Shriners Hospitals for Children grants 85127 (to B.E.U. and C.L.C.) and 84702 (to A.A.). The authors acknowledge the Shriners Hospitals for Children in Boston Morphology and Image Analysis and Translational Regenerative Medicine Special Shared Facilities and Yibin Chen for technical assistance. Funding Information: Electron microscopy was performed at the Schepens Eye Institute core facility supported by National Institutes of Health National Eye Institute Core Grant P30EY003790. Briefly, samples were dehydrated in graded ethanol solutions and critical point-dried using a Samdri 795 Critical Point Dryer (Tousimis, Rockville, MD), then mounted onto aluminum stubs, and chromium coated with a Gatan High-Resolution Ion Beam Coater (Gatan, Inc., Pleasanton, CA). Samples were imaged using a JEOL JSM-7401F Field Emission Scanning Electron Microscope (JEOL, Inc., Peabody, MA) to provide a qualitative assessment of the scaffold architecture after decellularization. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Background: The 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. Existing studies investigated the use of primates as a source of implants. The authors hypothesized that the porcine nipple can serve as a perfect shape-supporting implant because of functional similarities to the human nipple. A decellularization protocol was developed to obtain an acellular nipple scaffold (ANS) for nipple reconstruction. Methods: Tissue samples were collected from eight disease-free female Yorkshire pigs (60 to 70 kg) and then decellularized. The decellularization efficiency and extracellular matrix 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 ANSs in a single Yorkshire pig (60 to 70 kg), respectively. Inflammation and adverse events were monitored daily based on local clinical signs. Results: The authors showed that all cellular structures and 96% of DNA [321.7 ± 57.6 ng DNA/mg wet tissue versus 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 an increase in glycosaminoglycan 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. Conclusion: This is a preliminary report of a novel promising ANS for nipple reconstruction, but more research is needed to validate results. Clinical Relevance Statement: Breast cancer is very common among women. Treatment involves mastectomy, but its consequences affect patient mental well-being, and can lead to depression. Nipple-areola complex reconstruction is critical, and existing methods lead to unsatisfactory outcomes.
AB - Background: The 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. Existing studies investigated the use of primates as a source of implants. The authors hypothesized that the porcine nipple can serve as a perfect shape-supporting implant because of functional similarities to the human nipple. A decellularization protocol was developed to obtain an acellular nipple scaffold (ANS) for nipple reconstruction. Methods: Tissue samples were collected from eight disease-free female Yorkshire pigs (60 to 70 kg) and then decellularized. The decellularization efficiency and extracellular matrix 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 ANSs in a single Yorkshire pig (60 to 70 kg), respectively. Inflammation and adverse events were monitored daily based on local clinical signs. Results: The authors showed that all cellular structures and 96% of DNA [321.7 ± 57.6 ng DNA/mg wet tissue versus 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 an increase in glycosaminoglycan 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. Conclusion: This is a preliminary report of a novel promising ANS for nipple reconstruction, but more research is needed to validate results. Clinical Relevance Statement: Breast cancer is very common among women. Treatment involves mastectomy, but its consequences affect patient mental well-being, and can lead to depression. Nipple-areola complex reconstruction is critical, and existing methods lead to unsatisfactory outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85151312611&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/PRS.0000000000009998
DO - https://doi.org/10.1097/PRS.0000000000009998
M3 - Article
C2 - 36472499
SN - 0032-1052
VL - 151
SP - 618E-629E
JO - Plastic and Reconstructive Surgery
JF - Plastic and Reconstructive Surgery
IS - 4
ER -