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Biodegradable shape memory polymers provide unique regenerative medicine approaches in minimally invasive surgeries. Once heated, thermally responsive shape memory polymer devices can be compressed, programmed to fit within a small profile, delivered in the cold programmed state, and expanded when heated to body temperature. We have previously developed a biodegradable shape memory elastomer (SME), poly(glycerol dodecanedioate) (PGD), with transition temperatures near 37°C exhibiting nonlinear elastic properties like numerous soft tissues. Using SMEs in the clinic requires disinfection and sterilization methods that conserve physiochemical, thermomechanical, and shape recovery properties. We evaluated disinfection protocols using 70% ethanol and UV254 nm for research applications and ethylene oxide (EtO) gas sterilization for clinical applications. Samples disinfected with ethanol for 0.5 and 1 min showed no changes in physiochemical material properties, but after 15 min showed slower recovery rates than controls (p < .05). EtO sterilization at 54.4°C decreased transition temperatures and shape recovery rate compared to EtO sterilization at 37.8°C (p < .01) and controls (p < .05). Aging samples for 9 months in a vacuum desiccator significantly reduced shape recovery, and the recovery rate in EtO sterilized samples compared to controls (p < .001). Cytotoxicity testing (ISO-10993.5C:2012) revealed media extractions from EtO sterilized samples, sterilized at 37.8°C, and high-density polyethylene negative control samples exhibit lower cytotoxicity (IC50) than Ethanol 1 min, UV 2 h, and EtO 54.4°C. Cell viability of NIH3T3 fibroblasts on sterilized surfaces was equivalent on EtO 37.7°C, EtO 54.4°C and Ethanol sterilized substrates. Finally, chromogenic bacterial endotoxin testing showed endotoxin levels were below the FDA prescribed levels for devices contacting blood and lymphatic tissues for ethanol 1 min, UV 120 min, EtO 37.7°C, EtO 54.4°C. These findings outline various disinfection and sterilization processes for research and pre-clinical application and provide a pathway for developing custom sterilization cycles for the translation of biomedical devices utilizing PGD shape memory polymers., (© 2022 Wiley Periodicals LLC.)

This study evaluated the performance of a new O 3 /H 2 O 2 mixed gas sterilization instrument for killing microorganisms and inactivating bacterial endotoxin at low temperatures. Sterility assurance level was achieved by an over 6-log reduction of Geobacillus stearothermophilus ATCC 12980, and the decimal reduction value was 0.77 min in sterilization mode. A reduction of over 3 logs in Limulus amebocyte lysate coagulation activity of purified endotoxin from Escherichia coli was observed after treatment in endotoxin-inactivation mode. The same inactivation ability was observed when treating dried bacterial cells. Biomaterials made of polymer or metal did not exhibit cytotoxicity after gas exposure at O 3 concentrations below 200 ppm. As the results of human cell-based pyrogen testing, significant amounts of endotoxin that were over the limit for medical devices contacting cerebrospinal fluid (2.15 EU/device) were detected on scissors washed with a washer-disinfector and sterilized with ethylene oxide or autoclaving. In contrast, endotoxin decreased to 0.29 ± 0.05 EU/device after O 3 /H 2 O 2 mixed gas sterilization in endotoxin-inactivation mode. Compared to conventional gas sterilization methods, O 3 /H 2 O 2 mixed gas has high sterilization ability and a strong capacity to inactivate endotoxin. It is expected that this sterilization technology will improve the safety of reusable medical devices and utensils for regenerative medicine., (© 2021 Wiley Periodicals LLC.)

Ethylene oxide (EO) gas is commonly used to sterilize medical devices. Bioavailable residual EO, however, presents a significant toxicity risk to patients. Residual EO is assessed using international standards describing extraction conditions for different medical device applications. We examine a series of polymers and explore different extraction conditions to determine residual EO. Materials were sterilized with EO and exhaustively extracted in water, in one of three organic solvents, or in air using thermal desorption. The EO exhaustively extracted varies significantly and is dictated by two factors: the EO that permeates the material during sterilization; and the effectiveness of the extraction protocol in flushing residual EO from the material. Extracted EO is maximized by a close matches between Hildebrand solubility parameters δ polymer , δ EO , and δ solvent . There remain complexities to resolve, however, because maximized EO uptake and detection are accompanied by great variability. These observations may inform protocols for material selection, sterilization, and EO extraction. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2455-2463, 2018., (© 2017 Wiley Periodicals, Inc.)

Half of the female population over age 50 years will experience pelvic organ prolapse. We suggest a new approach based on tissue engineering principles to functionally reconstruct the anatomical structures of the pelvic floor. The aim of this study is to investigate the mechanical performance and effect on collagen and elastin production of a degradable mesh releasing basic fibroblast growth factor (bFGF). Implantation of biodegradable mesh with or without bFGF in their core has been conducted in 40 rats in an abdominal wall defect model. Samples were explanted after 4, 8, and 24 weeks, and tested for mechanical properties and the composition of connective tissue. The study showed an increase in mRNA expression for collagen-I (p = 0.0060) and collagen-III (p = 0.0086) in the 4 weeks group with bFGF. The difference was equalized at 8 and 24 weeks. No difference was found at any time for protein amount for collagen-I, collagen-III, and fibronectin. The amount of collagen decreased from 4 to 24 weeks but the fraction of collagen increased. The maximal load of the newly formed tissue showed no effect of bFGF at any time. Exclusively, histology showed a limited ingrowth of collagen fibers after 4 weeks with bFGF but signs of elastin fibers were seen at 24 weeks. The investigation showed that a biodegradable mesh promotes tissue formation with a promising strength. The mesh with bFGF did not represent any advantage on either long or short term in comparison to the mesh without bFGF. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 680-688, 2018., (© 2017 Wiley Periodicals, Inc.)

The surfaces of three chitosan samples, differing only in their degrees of deacetylation and of carboxyethyl chitosan were chemically characterized by X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectroscopy, X-ray diffraction, and Fourier transform infrared, both before and after sterilization with ethylene oxide. Unexpected elemental ratios suggest that surface chemical modification occurred during the processing of the original chitin, with further surface modification on subsequent sterilization, despite previous reports to the contrary. Cell viability was evaluated by direct contact methyl thiazole tetrazolium and lactate dehydrogenase assays between the chitosan particles and A549 human epithelial cells, which demonstrated that the modifications incurred on sterilization are reflected in biocompatibility changes. All the samples were found to be biocompatible and nontoxic before sterilization and remained so subsequently., (Copyright © 2013 Wiley Periodicals, Inc.)

In this study, the in vivo wear of highly cross-linked polyethylene (CLPE) cups against alumina ceramic femoral heads was evaluated by radiographic and retrieval analysis. The radiographic wear of six ethylene oxide gas-sterilized (i.e., non-cross-linked) conventional polyethylene (PE) cups with the mean follow-up of 20.9 years and 60 CLPE cups with the mean follow-up of 7.4 years was measured. The retrieved 16 PE cups with clinical use for mean 21.5 years and 10 CLPE cups with clinical use for mean 2.9 years was evaluated as a retrieval analysis. In the radiographic analysis, the linear wear of CLPE cups was significantly lower (99% reduction) compared to conventional polyethylene cups. The results of retrieval analyses for both cups were similar to those of radiographic analyses. Even when third-body wear occurred during clinical use, no surface damage was observed on the surface of ceramic femoral heads. The surface is not sensitive to third-body wear, and hence, the ceramic femoral head has a great advantage in terms of the wear of CLPE under third-body wear conditions. In conclusion, CLPE cups used with alumina ceramic femoral heads in total hip arthroplasty should have favorable wear resistance in several in vivo situations., (Copyright © 2013 Wiley Periodicals, Inc.)

Sterilization conditions need to be optimized to effectively neutralize the bioburden while using short exposure times for minimizing the changes in chemical composition, material properties and device architecture. Towards this goal, effects of ethylene oxide (EtO) exposure parameters such as time, temperature, humidity, and EtO concentration on the polymer properties were investigated by monitoring the changes in composition, and the morphology of different types of structures in a family of poly(ethylene glycol) (PEG)-containing tyrosine-derived polycarbonates. EtO was found to esterify the carboxyl groups present in the desaminotyrosyl-tyrosine groups. Sterilization under conditions more severe than those normally used reduced the glass transition temperature (Tg) and the molecular weight of the polymers, and the presence of PEG in the polymer enhanced this effect. Furthermore, electron micrographs showed that EtO sterilization cycle conditions, even those considered "mild," were found to damage the fragile structures such as those found in electrospun mats and porous scaffolds. Our study shows that the presence of EtO-susceptible groups, fusible architecture, and surface morphology should be taken into account in choosing the appropriate EtO sterilization conditions., (Copyright © 2013 Wiley Periodicals, Inc.)

Most studies on the intervertebral disc (IVD) focus on the regeneration of the nucleus pulposus (NP). However, without a proper strategy to regenerate the damaged annulus fibrosus (AF), the NP replacements are bound to fail. Therefore the objective of this study was to investigate whether the use of bone marrow-derived mesenchymal stem cells (BMSCs) to form cell sheets, and incorporating them onto silk scaffolds, has the potential to regenerate the annulus fibrosus. The BMSC cell sheets and silk scaffolds were wrapped around a silicone NP substitute to form a simulated IVD-like assembly. The simulated IVD-like assembly was cultured for 4 weeks in static conditions and it was shown that the BMSC cell sheets remained viable, with no significant change in cell numbers. Histological analysis showed that the BMSC cell sheets adhered well onto the silk scaffolds and glycosaminoglycans (GAGs) were detected within the extracellular matrix (ECM). The ratio of collagen type I to collagen type II within the ECM of the BMSC cell sheets also decreased significantly over the period of culture. The results suggested that extensive remodelling of the ECM occurred within the simulated IVD-like assembly, and it is suitable for the regeneration of the inner AF., (Copyright © 2011 John Wiley & Sons, Ltd.)

In this study, mesenchymal stem cells (MSCs) embedded in biodegradable and water-swollen, elastic block copolymer scaffolds were assessed for MSC chondrogenesis. To determine the optimal conditions for chondrogenesis of the embedded rMSCs, transforming growth factor-beta 3 (TGF-beta 3) was physically conjugated with chondroitin sulfate (CS) and mixed into scaffolds, which were subsequently evaluated for the differentiation of transplanted rMSCs. In determination of CS-bound growth factors for chondrogenesis, scaffold mixed with rMSCs and TGF-beta 3 was then tested by growth factor release profiles, confocal laser microscopy, RT-PCR analysis, real time-QPCR, and histology. The results of several different analyses of the transplanted rMSCs embedded in the scaffolds showed that rMSCs coupled with a CS-bound TGF-beta 3 encapsulated scaffold evidenced superior cartilage tissue formation as measured by an assay of specific gene and protein expression. Moreover, the scaffold exhibited more rapid and more distinct morphology of differentiated rMSCs than was observed with other scaffolds, as determined by histology and immunochemical histology analysis. These results indicate that the elastic block copolymer scaffolds combined with a CS-bound TGF-beta 3 should prove very suitable matrix for cell-based cartilage tissue engineering., ((c) 2009 Wiley Periodicals, Inc.)

Objectives: This study examined the emission characteristics of ethylene oxide (EO)-sterilized syringes under various environmental conditions, aiming to develop control strategies to minimize worker exposure., Methods: Experiments were performed in a facility in which temperature, relative humidity (RH), and air change rate (ACR) were controlled., Results: Analytical results indicate that the main effects of the four test variables on kinetic parameters were statistically significant (p < 0.05), except for the effect of the product on the decay rate constant, the effect of ACR on maximum EO concentration, and effect of RH on the area under the curve-days 1 and 2. The interactive effects among test variables were also evident, indicating complex emission behaviors. The mean EO emission factors during the days 1 and 2 and at the 48th hour for the 1- and 30-ml products were 2302, 1301, and 1031 mg/m(3)/h, and 871, 490, and 381 mg/m(3)/h, respectively. The times required for air EO concentrations from tested products to return to approximately 0 and 1 ppm (permissible limit) were 417 and 218 h, respectively., Conclusions: Plastic content, temperature, RH, and ACR affected EO emissions. ACR is an achievable means of control; however, the aeration area/system should be isolated to ensure adequate ventilation is achieved.

In the treatment of chronic wounds, it is necessary to establish a physiological wound milieu to improve healing. Application of collagen as wound dressing has been described as beneficial as it possesses the ability to reduce elevated levels of proteases, cytokines, and free radicals. Consequently, a wide range of wound dressings based on collagen have been developed. Native collagen is susceptible to alterations because of influences during the production process; to minimize effects on the molecule itself collagen wound dressings are usually aseptically produced. Common sterilization methods (autoclaving, irradiation, and ethylene oxide (EtO) treatment) can induce changes in the protein chemistry and physical properties, potentially affecting the absorption rate, mechanical strength, or performance. In this study, we have evaluated the influence of gamma- and beta-irradiation as well as EtO sterilization on the binding capacity of collagen type I for selected proteases and cytokines associated with nonhealing wounds. Although a pronounced effect on the physical properties of the collagen was found, there was no significant loss in the binding affinity for polymorphonuclear elastase, matrix metalloproteinase-2, and interleukin-1beta, or in the antioxidant capacity.

Zirconia/alumina composite ceramics have been recently developed for total hip arthroplasty because of their excellent mechanical properties and tribologic characteristics. All such materials used clinically must be easily sterilized, but no report has been issued concerning methods for sterilizing zirconia/alumina composite hip prostheses. Here, we show that 50 kGy of gamma irradiation effectively sterilizes both the surfaces and interiors of these materials. In addition, it was found that the commonly used ethylene oxide and 25-kGy gamma irradiation sterilization methods inadequately sterilize deep inside the femoral head. Moreover, no changes in the chemical or mechanical properties of the composites were noted after exposure to 50-kGy gamma irradiation. We suggest that 50-kGy gamma irradiation is an optimal sterilization method for zirconia/alumina composite total hip replacements.

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., ((c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.)

Microspheres fabricated by biodegradable polymers with tunable surface properties show great potentials as microcarriers in in vitro cell cultivation and tissue engineering. Herein we reported a new method to regulate the surface property and morphology of microspheres via the synthesis of biodegradable amphiphilic block copolymers with adjustable compositions. The poly(epsilon-caprolactone-b-ethylene oxide) diblock copolymers with functional amino end groups bonding to the PEO block (PCL-b-PEO-NH(2)) were synthesized by sequential ring-opening polymerization with potassium bis(trimethylsilyl) amide as initiator. The copolymers were characterized by gel permeation chromatography (GPC) and (1)H NMR, and then used to fabricate microspheres by w/o/w double emulsion solvent evaporation technique. The surface properties of microspheres were studied by means of scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results indicated that both the fabrication conditions and copolymer composition have great influences on the surface morphology and property of microspheres. The reactive amino functional groups are dominantly located on the surface of microspheres. The in vitro degradation of microspheres was studied by following the morphological changes of microspheres. The influences of hydrophilic PEO out-layers on the enzymatic degradation of microspheres were discussed. These microspheres with controllable surface morphology and amino functional groups are expected to be promising alternatives for the further biomimetic modification to promote cell growth on materials., ((c) 2007 Wiley Periodicals, Inc.)

This study examined the effect of ethylene oxide (EtO) and electron beam (e-beam) irradiation on the properties of 70:30 poly(L-lactide-co-D,L-lactide). The effects of sterilization upon the polymer physical characteristics and strength retention of the material were examined, both initially and after being subjected to real time ageing. Commercially available 70:30 poly(L-lactide-co-D,L-lactide) material was fabricated into rectangular, cylindrical, screw, and sheet designs, and tested in compression, shear, or tension. Sterilization of 70:30 poly(L-lactide-co-D,L-lactide) by ethylene oxide had a nearly negligible effect on the physical properties of the polymer, regardless of specimen size or manufacturing technique. The molecular weight and inherent viscosity of the specimens decreased by approximately 3% after sterilization by EtO. However, sterilization of 70:30 poly(L-lactide-co-D,L-lactide) by e-beam irradiation resulted in immediate changes to some of the physical properties of the polymer. Specimens sterilized by e-beam irradiation displayed an immediate decrease in inherent viscosity of approximately 67% as compared to the respective nonsterile samples. The immediate decrease in inherent viscosity and molecular weight with e-beam irradiation required approximately 39 weeks of real time ageing of the EtO sterilized parts. At all time points investigated in the present study, the strength retention of the EtO sterilized devices equaled or exceeded that of the e-beam irradiated samples.

In this study, the process of manufacturing and sterilizing an orthopedic implant constructed from poly(L-lactic acid) (PLLA) was closely simulated. The hydrogen peroxide gas plasma (HPGP) sterilization process was comparatively investigated against ethylene oxide (EtO). Characterization of the physical, thermal, mechanical, morphological, and chemical properties was monitored. The results indicate that the HPGP sterilization process did not have a significant influence on M(n) or M(w) initially or through 12 weeks of in vitro conditioning when compared with EtO. Only indications of physical aging were evident in the analysis of the thermal and mechanical properties by differential scanning calorimeter and tensile testing for each sterilization processes. Using wide angle X-ray diffraction to determine morphology characteristics, it was determined that no changes were observed between the as molded, HPGP, and EtO specimens initially or through the 12 week in vitro conditioning period. Contact angle measurements revealed a significant reduction in the surface energy following treatment by the HPGP process, suggesting the formation of polar groups. However, surface chemistry analysis by ATR-FTIR indicated no significant chemical modification from either sterilization method. PLLA showed intermediate levels of residual hydrogen peroxide absorption following processing by HPGP., (2006 Wiley Periodicals, Inc.)

Much attention has been directed toward developing dental direct restorative composites that generate less shrinkage stress during setting. The aim of this study was to explore the viscoelastic behavior of a new class of low-shrinkage dental restorative composite during setting. The setting behavior of an experimental oxirane composite has been investigated by analyzing stress-strain data with two-parametric mechanical models. Experimental data were obtained from a dynamic test method, in which the setting light-activated composite was continuously subjected to sinusoidal strain cycles. The material parameters and the model's predictive capacity were analyzed with validated modeling procedures. The light-activated oxirane composite exhibited shrinkage delay and low polymerization shrinkage strain and stresses when compared with conventional light-activated composite. Noise in the stress data restricted the predictive ability of the Maxwell model to the elastic modulus development of the composite only. Evaluation tests of their potential as restorative material are required, to examine if the biocompatibility and mechanical properties after setting of oxirane composites are acceptable for dental use., ((c) 2005 Wiley Periodicals, Inc.)