Effects of sterilization on poly(ethylene glycol) hydrogels

Abstract

The past few decades have witnessed a dramatic increase in the development of polymeric biomaterials. These biomaterials have to undergo a sterilization procedure before implantation. However, many sterilization procedures have been shown to profoundly affect polymer properties. Poly(ethylene glycol) hydrogels have gained increasing importance in the controlled delivery of therapeutics and in tissue engineering. We evaluated the effect of ethylene oxide (EtO), hydrogen peroxide (H(2)O(2)), and gamma sterilization of poly(ethylene glycol) hydrogels on properties relevant to controlled drug delivery and tissue engineering. We observed that the release of cyclosporine (CyA) (an immunosuppressive drug that is effective in combating tissue rejection following organ transplantation) was significantly affected by the type of sterilization. However, that was not the case with rhodamine B, a dye. Hence, the drug release characteristics were observed to be dependent not only on the sterilization procedure but also on the type of agent that needs to be delivered. In addition, differences in the swelling ratios for the sterilized and unsterilized hydrogels were statistically significant for 1:1 crosslinked hydrogels derived from the 8000 MW polymer. Significant differences were also observed for gamma sterilization for 1:1 crosslinked hydrogels derived from the 3350 MW polymer and also the 2:1 crosslinked hydrogels derived from the 8000 MW polymer. Atomic force microscopy (AFM) studies revealed that the roughness parameter for the unsterilized and EtO-sterilized PEG hydrogels remained similar. However, a statistically significant reduction of the roughness parameter was observed for the H(2)O(2) and gamma-sterilized samples. Electron spin resonance (ESR) studies on the unsterilized and the sterilized samples revealed the presence of the peroxy and the triphenyl methyl carbon radical in the samples. The gamma and the H(2)O(2)-sterilized samples were observed to have a much higher concentration of the radical pecies when compared with the EtO and the unsterilized samples.

Drying and storage effects on poly(ethylene glycol) hydrogel mechanical properties and bioactivity

“…Considerable attention has already been given to the effects of various sterilization procedures on the fragile hydrogel structure. For example, steam and gamma radiation sterilization severely were shown to compromise PEGDA hydrogel structure, whereas dense-carbon-dioxide sterilization effectively eliminated bacterial spores with minimal or no effects on hydrogel properties 31,63 . In addition, PEGDA and PEGDA-collagen hydrogels exhibited similar endothelial cell adhesion and morphology after vacuum drying and ethylene oxide sterilization as compared with untreated hydrogels 19 .…”

“…These treatments may alter the structure of the scaffold and compromise in vivo performance. Although the effects of sterilization on PEG hydrogel properties have been reported in the literature 31 , few studies have addressed how processing and storage may affect hydrogel mechanical properties and bioactivity. Maintenance of scaffold properties and the desired cellmaterial interactions are especially important for bioactive scaffolds, as cells could respond acutely to small changes in the implant 25, 32 .…”

Application of a dense gas technique for sterilizing soft biomaterials

“…Since it is known that gamma radiation can affect the physicochemical properties and morphology of polymers and gels (Kanjickal et al, 2008), the effect of gamma irradiation on the morphology of the gels were first tested. While the radiation dose used for sterilization depends on the type of material or polymer being sterilized, a typical dose for achieving effective sterilization is 2.5 Megarad (Mrad; Clough, 2001).…”

Multifunctional nanoparticles for brain tumor imaging and therapy

“…during the early stages of production that can be consistently reproduced on a larger scale and yield a consistent product that has the same structure and properties as the nanoparticles synthesized in the laboratory [244]. Furthermore, if it is required that the nanoparticles are sterile during administration, an appropriate sterilization technique must be selected because nanoparticles are susceptible to damage from gamma irradiation and autoclaving [245–247]. Moreover, in order to regulate the nanoparticles during synthesis, quick and reliable in-process analytic characterization is required to ensure that the manufacturing process does not alter the composition as well as compromise the quality and stability of the final product.…”