Peracetic Acid: A Practical Agent for Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds

Abstract

Advanced biomaterials and sophisticated processing technologies aim at fabricating tissue-engineering scaffolds that can predictably interact within a biological environment at the cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed before clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam, and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone, a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to 0°. Therefore, PAA can provide economical, rapid, and effective sterilization of heat-sensitive polymeric electrospun scaffolds that are used in tissue engineering.

Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance

“…The combination of ammonium hydroxide and Triton X-100 is effective for decellularization and maintains mechanical properties better than SDS/ logic scaffolds and has also been shown to be an effective steriliza-694 tion method for polymeric scaffolds [137]. However, incubation 695 with acid may not provide sufficient penetration of ECM bioscaf-696 folds to achieve satisfactory sterilization.…”

“…Each of the protocols also 135 required an endonuclease (DNase and/or RNase) to remove resid- 136 ual nucleic acids. It is noteworthy that the measurement of 137 decellularization efficacy used in each study was unique and com-138 mon criteria were not used. Decellularization efficacy is discussed 139 in more detail in a later section.…”

Effect of Sterilization Methods on Electrospun Poly(lactic acid) (PLA) Fiber Alignment for Biomedical Applications

“…Although innovative methodologies (hydrogen peroxide gas plasma, ozone, chlorine dioxide, pulse light, microwave radiation, among others) are being developed in recent years focused in sensitive biomedical devices, the traditional methods are already well established in the industry and have a long history of safe and effective use, being recognized by FDA 19 . Among conventional methods, dry and moist heat sterilizations are known to be harsh methods for thermosensitive polymers, inducing thermal degradation and structural changes 20 . Ethylene oxide (EO) emerged as a cost-effective, low-temperature process widely used for polymeric devices sterilization, that acts through its strong alkylating power 21 .…”

Mechanism of Bacillus subtilis spore inactivation by and resistance to supercritical CO2 plus peracetic acid

“…Because of the poor efficiency of spore inactivation by scCO 2 alone at moderate temperatures, a variety of chemicals have been added to scCO 2 in order to increase spore inactivation, including acetic anhydride, hydrogen peroxide (H 2 O 2 ), peracetic acid (PAA), PAA plus octanoic acid, trifluoroacetic acid, formic acid or alcohols (White et al 2006;Nichols et al 2009;Qiu et al 2009;Shieh et al 2009;Checinska et al 2011;Howell et al 2012;Russell et al 2013;Yoganarasimha et al 2014;Bernhardt et al 2015). Other variations on scCO 2 have also been tested for inactivating spores of Bacillus species, including microbubbles of scCO 2 and scCO 2 treatment following a pulsed electric field treatment that sensitizes spores to scCO 2 (Ishikawa et al 1997;Spilimbergo et al 2003).…”