Characterization of an Acellular Scaffold for a Tissue Engineering Approach to the Nipple-Areolar Complex Reconstruction

Abstract

A significant number of patients undergo mastectomies and breast reconstructions every year using many surgical-based techniques to reconstruct the nipple-areolar complex (NAC). Described herein is a tissue engineering approach that may permit a human NAC onlay graft during breast reconstruction procedures. By applying decellularization, which is the removal of cellular components from tissue, to an intact whole donor NAC, the extracellular matrix (ECM) structure of the NAC is preserved. This creates a biologically derived scaffold for cells to repopulate and regenerate the NAC. A detergent-based decellularization method was used to derive whole NAC scaffolds from nonhuman primate rhesus macaque NAC tissue. Using both histological and quantitative analyses for the native and decellularized tissues, the derived ECM graft was assessed. The bioactivity of the scaffold was evaluated following cell culture with bone marrow-derived mesenchymal stem cells (BMSCs). The data presented here demonstrate that scaffolds are devoid of cells and retain ECM integrity and a high degree of bioactivity. The content of collagen and glycosaminoglycans were not significantly altered by the decellularization process, whereas the elastin content was significantly decreased. The proliferation and apoptosis of seeded BMSCs were found to be approximately 65 and <1.5%, respectively. This study characterizes the successful decellularization of NAC tissue as compared to native NACs based on structural protein composition, lubricating protein retention, the maintenance of adhesion molecules, and bioactivity when reseeded with cells. These histological and quantitative analyses provide the foundation for a novel approach to NAC reconstruction.

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume

“…ECM can be derived from a variety of tissue sources (e.g. urinary bladder, skin, CNS) [3] and has found translation into a clinical setting to repair urinary bladder, muscle, peripheral nerve and heart, as well as being used in breast reconstruction [4-8]. …”

Engineered Meniscus Scaffolds using Sonication Decellularization Treatment System

“…Based on the van gieson staining and genomic DNA quantification, the sonication decellularization treat ment system successfully decellu larized meniscus tissues with absence of blueblack nucleus stained and significantly low residual DNA content compared to native tissues. Further confirmation of decellularizat ion process was completed through gel electrophoresis of purified DNA as previously done as shown in Figure 3 that portrayed the DNA frag ments and bands [20]. For sonication decellularized scaffolds, there was absence of any DNA frag ments or bands.…”

Tissue engineering and regenerative medicine strategies for the female breast

“…Not only has adipose tissue regeneration been studied on biological scaffolds. Pashos et al () described a tissue‐engineering approach for nipple‐areola complex reconstruction. They decellularized a whole donor NAC, maintaining the extracellular matrix structure unaltered (Figure ).…”

“…The decellularized NAC also maintained the cell adhesion molecules (fibronectin and laminin). They employed their own protocol to conduct the study decellularizing the NAC tissues of rhesus macaque (Pashos et al, ).…”

“…The decellularized NAC also maintained the cell adhesion molecules (fibronectin and laminin). They employed their own protocol to conduct the study decellularizing the NAC tissues of rhesus macaque(Pashos et al, 2017).They then conducted several analyses: genomic DNA, fragment and histological analysis and protein, GAGs, collagen, and elastin quantification. These produced good results in terms of efficient cell removal, DNA content reduction, and preservation of collagen fiber patterns.…”