Safety and performance of surgical adhesives.

BACKGROUND: Tissue adhesives are an alternative to conventional surgical sutures to reduce the time and cost of wound closure and to improve patient comfort. The use of tissue adhesives does not require any subsequent intervention and significantly lowers the volume and rate of blood loss, and reduces the need for transfusions during and after surgery. However, based on their formulation, tissue adhesives' safety profile and functional properties may differ. Therefore, this study aimed to evaluate the basic safety and performance of NE'X Glue® Surgical Sealant, BioGlue® Surgical Sealant, and PREVELEAKTM Surgical Sealant in vitro. METHODS: The basic safety of commercially available tissue adhesives was evaluated using MEM elution assay according to ISO 10993-5 and endotoxin level according to 85. USP. The in vitro performance was evaluated using lap-shear by tension loading test, burst strength test, degradation, and swelling assays. RESULTS: NE'X Glue®, BioGlue®, and PREVELEAKTM did not cause cytotoxicity in MEM elution assay. All surgical adhesives are below the general limit of endotoxin contamination of 20 EU/device. NE'X Glue® and BioGlue® showed the highest and comparable strength properties in lap shear and burst strength tests compared to PREVELEAKTM. NE'X Glue® and PREVELEAKTM are characterized by lower degradation potential than BioGlue®. PREVELEAKTM is characterized by the highest swelling when compared to NE'X Glue® and BioGlue®. CONCLUSIONS: NE'X Glue® is most versatile in terms of functional properties while maintaining the same safety profile as BioGlue® and PREVELEAKTM.

Can supernatant from immortalized adipose tissue MSC replace cell therapy? An in vitro study in chronic wounds model.

BACKGROUND: Mesenchymal stem cells (MSCs) secrete a cocktail of growth factors and cytokines, which could promote tissue regeneration and wound healing. Therefore, in clinical practice, post-culture MSC supernatant treatment could be a more attractive alternative to autologous stem cell transplantation. In this study, we compared the regenerative properties of supernatants harvested from four newly established human adipose tissue mesenchymal stem cell lines (HATMSCs) derived from chronic wound patients or healthy donors. METHODS: HATMSC supernatants were produced in a serum-free medium under hypoxia and their content was analyzed by a human angiogenesis antibody array. The regenerative effect of HATMSCs supernatants was investigated in an in vitro model of chronic wound, where cells originating from human skin, such as microvascular endothelial cells (HSkMEC.2), keratinocytes (HaCaT), and fibroblasts (MSU-1.1), were cultured in serum-free and oxygen-reduced conditions. The effect of supernatant treatment was evaluated using an MTT assay and light microscopy. In addition, fibroblasts and HATMSCs were labeled with PKH67 and PKH26 dye, respectively, and the effect of supernatant treatment was compared to that obtained when fibroblasts and HATMSCs were co-cultured, using flow cytometry and fluorescent microscopy. RESULTS: A wide panel of angiogenesis-associated cytokines such as angiogenin, growth-regulated oncogene (GRO), interleukin-6 and 8 (IL-6, IL-8), vascular endothelial growth factor (VEGF), insulin growth factor 1 (IGF-1), and matrix metalloproteinase (MMP) were found in all tested HATMSCs supernatants. Moreover, supernatant treatment significantly enhanced the survival of fibroblasts, endothelial cells, and keratinocytes in our chronic wound model in vitro. Importantly, we have shown that in in vitro settings, HATMSC supernatant treatment results in superior fibroblast proliferation than in the case of co-culture with HATMSCs. CONCLUSIONS: Our results suggest that therapy based on bioactive factors released by the immortalized atMSC into supernatant has important effect on skin-derived cell proliferation and might preclude the need for a more expensive and difficult cell therapy approach to improve chronic wound healing.