Adipose-Derived Stem-Cell-Seeded Non-Cross-Linked Porcine Acellular Dermal Matrix Increases Cellular Infiltration, Vascular Infiltration, and Mechanical Strength of Ventral Hernia Repairs

Abstract

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh-non-cross-linked porcine acellular dermal matrix (ncl-PADM)-used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5 · 10 4 cells/cm 2 ) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2 · 4 cm) were created and repaired with ASC-seeded (n = 31) and control (n = 32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group ( p < 0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points ( p < 0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group ( p < 0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes.

Current wound healing procedures and potential care

“…Adipose derived stem cells (ADSCs) have been attracted much attention due to their early isolation, relative abundance and multipotency [122]. ADSCs can be harvested by liposuction procedure eliminating the tissue damage [122–124]. ADSCs also release angiogenic factors which stimulate angiogenesis required for healthy wound repair [123–125].…”

Extracellular matrix scaffolds for treatment of large volume muscle injuries: A review

“…The addition of autologous or allogeneic muscle progenitor cells, satellite cells, mesenchymal stem cells, or adipose‐derived stem cells to ECM has been explored for VML treatment . Cell‐seeded ECM scaffolds seek to combine the proregenerative features of cellular and matrix factors to enhance overall regenerative capacity.…”

Enigmatic aetiology of inguinal hernia

“…29,30 The effect of calcitonin gene related peptide could be mediated by this growth factor acting directly on the epithelial cells. 31,32 After considering a wide variety of factors the final factor which needs consideration is the transversalis fascia. 33 Dissection of normal groins for non-hernia diseases such as lipoma of the cord or for varicocele ligations revealed two anatomically distinct layers.…”