Effect of Ethylene Oxide Sterilization on Polyvinyl Alcohol Hydrogel Compared with Gamma Radiation

Abstract

This study investigated the effects of terminal sterilization of polyvinyl alcohol (PVA) biomaterials using clinically translatable techniques, specifically ethylene oxide (EtO) and gamma (g) irradiation. While a few studies have reported the possibility of sterilizing PVA with g-radiation, the use of EtO sterilization of PVA requires additional study. PVA solutions were chemically crosslinked with trisodium trimetaphosphate and sodium hydroxide. The three experimental groups included untreated control, EtO, and g-irradiation, which were tested for the degree of swelling and water content, and mechanical properties such as radial compliance, longitudinal tensile, minimum bend radius, burst pressure, and suture retention strength. In addition, samples were characterized with scanning electron microscopy, differential scanning calorimetry, X-ray photoelectron spectroscopy, and water contact angle measurements. Cell attachment was assessed using the endothelial cell line EA.hy926, and the sterilized PVA cytotoxicity was studied with a live/dead stain. Platelet and fibrin accumulation was measured using an ex vivo shunt baboon model. Finally, the immune responses of PVA implants were analyzed after a 21-day subcutaneous implantation in rats and a 30-day implantation in baboon. EtO sterilization reduced the PVA graft wall thickness, its degree of swelling, and water content compared with both g-irradiated and untreated PVA. Moreover, EtO sterilization significantly reduced the radial compliance and increased Young's modulus. EtO did not change PVA hydrophilicity, while g-irradiation increased the water contact angle of the PVA. Consequently, endothelial cell attachment on the EtO-sterilized PVA showed similar results to the untreated PVA, while cell attachment significantly improved on the g-irradiated PVA. When exposing the PVA grafts to circulating whole blood, fibrin accumulation of EtO-sterilized PVA was found to be significantly lower than g-irradiated PVA. The immune responses of g-irradiated PVA, EtO-treated PVA, and untreated PVA were compared. Implanted EtO-treated PVA showed the least MAC387 reaction. The terminal sterilization methods in this study changed PVA hydrogel properties; nevertheless, based on the characterizations performed, both sterilization methods were suitable for sterilizing PVA. We concluded that EtO can be used as an alternative method to sterilize PVA hydrogel material.

Regeneration of skeletal system with genipin crosslinked biomaterials

“…To reduce graft contamination, the harvested tendon generally needs to be sterilized, and gamma radiation is one of the effective methods to eliminate infection. 134,135 However, high-energy radiation damages the collagen Figure 7. Constructing an injectable nucleus pulposus scaffold based on decellularized nucleus pulposus (dNP): (a) decellularized nucleus pulposus (dNP)/chitosan/ADSCs/genipin composite material for rabbit nucleus pulposus regeneration, (b) expression of chondrogenic genes (Acan, Col2 and Sox9) at 7 and 14 days of incubation, and (c) hematoxylin and eosin (H&E) and safranin O staining of repaired nucleus pulposus tissue at 16 weeks after implantation.…”

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

“…[280] The thrombin generation was slightly increased on gamma treated surface, [281] while EC density was significantly increased. [281,282] EO sterilization is suitable for polymer implants, but influences their physicochemical properties. [283] Importantly, EO sterilization can been used for scaffolds modified by active molecules.…”

Quantifying Physical Thrombus Characteristics on Cardiovascular Biomaterials Using MicroCT

“…The luminal surfaces were then modified using a variety of techniques, including biochemical and topographical modifications, and assessed for thrombogenesis and hemocompatibility in the ex vivo shunt whole blood test. Specific modifications included integration of the peptide sequence Gly-Phe-Pro-Gly-Glu-Arg (GFPGER), plasma modification, addition of gelatin with a carbonyldiimidazole (CDI) covalent linker, and sterilization, and their preparation methods are described in greater detail in previous publications [16][17][18][19]. Samples, which were modified by the integration of GFPGER, a peptide subsequence of type I collagen, had GFPGER mixed with the STMP in the PVA manufacturing process [17].…”

“…The PVA for the gelatin-modified samples were activated using CDI with the goal of conjugating a gelatin protein, as described previously [18]. Additionally, unmodified PVA samples were subjected to terminal sterilization using ethylene oxide (EtO) and gamma radiation after cross-linking and before implantation, as described previously [19]. Following manufacturing and surface modifications, PVA grafts were assembled for testing by attaching each graft to silicone tubing (Technical Products, Inc.) using heat shrink (Small Parts, Inc.) tubing connectors.…”

“…Specifically, ePTFE served as a clinical control; collagen-coated ePTFE acted as a positive, thrombogenic control; and poly(vinyl alcohol) (PVA) served as a preclinical, non-thrombogenic, hydrogel material. Several surface modifications of the PVA, which were previously evaluated for their hemocompatibility and endothelialization potential [16][17][18][19], were used in this work to assess and validate the measurement of the physical properties of the thrombus. Advanced image software analysis was then used to quantify the luminal volume (the inverse of thrombus volume) and the intra-thrombus variability.…”