Combined injury: irradiation with skin or bone wounds in rodent models.

A radiation combined injury is defined as an injury that occurs in the setting of irradiation, such as those expected after a nuclear accident, radiation dispersal device release (a 'dirty bomb'), or a nuclear weapon detonation. There is much research on irradiation-associated burns and their healing, but there is less known about other injuries sustained in the context of irradiation. Animal models are limited in their correlations to clinical situations but can support research on specific questions about injuries and their healing. Mouse models of irradiation with skin or bone wounds are validated as highly reproducible and quantitative. They show dose-dependent impairment of wound healing, with later recovery. Irradiation-induced delay of bone wound healing was mitigated to different extents by single doses of gramicidin S-nitroxide JP4-039, a plasmid expressing manganese superoxide dismutase, amifostine/WR2721, or the bifunctional sulfoxide MMS-350. These models should be useful for research on mechanisms of radiation dermal and osseous damage and for further development of new radioprotectors. They also provide information of potential relevance to the effects of clinical radiation therapies.

Ultra-high molecular weight polyethylene (UHMWPE) for hip and knee arthroplasty: The present and the future.

PURPOSE: to review advances and clinical performance of polyethylene in total joint arthroplasty, summing up historical problems and focusing on the latest innovations. METHODS: search for medical grade Ultra-High-Molecular-Weight-Polyethylene (UHMWPE); Data Sources: PubMed, Scopus, Cochrane Library. RESULTS: the increasing number of joint arthroplasties and high-activity patients led to progressive developments of bearing surfaces to improve performance and durability. Different strategies such as crosslinking UHMWPE (HXLPE) and the addition of vitamin-E (HXLPE) have been tested to improve wear and oxidation resistance. CONCLUSION: Recent innovations about UHMWPE showed improvements either for hip and knee, with the potential of long-term survivorship.

Mechanical Properties of the Every Second Matters for Mothers-Uterine Balloon Tamponade (ESM-UBT) Device: In Vitro Tests.

Objective Postpartum hemorrhage (PPH) is the most common cause of maternal mortality and morbidity worldwide, most of which occurs in resource-poor settings. Placement of a uterine balloon may be life-saving in uncontrolled PPH. The Every Second Matters for Mothers-Uterine Balloon Tamponade (ESM-UBT) device is an ultra-low-cost uterine balloon designed for global access. The purpose of this study was to evaluate the mechanical properties of the ESM-UBT device. Study design Intraluminal pressures, diameters, and burst volumes of condom uterine balloons and Foley catheter balloons of ESM-UBT devices were measured in open air and inside uterus models. Condom uterine balloons were tested with uterus model sizes of 100, 250, and 500mL. The condom-catheter O-ring attachment tensile strength was also evaluated. Results All 28 samples of ESM-UBT condom uterine balloons maintained their integrity for at least 3 hours when subjected to pressures of 200 mm Hg or greater across each of the tested uterine volumes. No Foley catheter balloons burst after instillation of 30mL, O-rings withstood forces of 15.4 ± 2.1 N, and condom uterine balloons stretched to 35.8 ± 2.1 cm without loss of integrity. Conclusion The mechanical properties of the ESM-UBT device make it attractive for scale across resource-poor settings.

Effects of micro/nano strontium-loaded surface implants on osseointegration in ovariectomized sheep.

BACKGROUND: Poor osseointegration of dental implants often occurs in osteoporotic patients and processed implant surfaces could help to improve the dilemma. PURPOSE: This study aimed to compare the effects of different titanium (Ti) surfaces on bone-implant osseointegration in ovariectomized (OVX) sheep. MATERIALS AND METHODS: Four groups were included: smooth titanium (ST) was merely polished Ti; micro titanium (MT) was treated with hydrofluoric acid (HF) for 30 minutes; strontium-loaded nano titanium (NT-Sr) was formed by magnetron sputtering; strontium-loaded micro/nano titanium (MNT-Sr) was fabricated by HF etching combined with magnetron sputtering. The biological responses were evaluated by human bone marrow-derived mesenchymal stem cells (hBMMSCs) experiments in vitro. Osseointegration was evaluated in vivo after each surface implant was inserted into OVX sheep' mandibles. RESULTS: The numbers of adhered and mineralized hBMMSCs increased significantly in the MNT-Sr group. The bone-implant contact and the maximal pull-out force increased significantly with MNT-Sr surface. The bone volume ratio and trabecular number of the MNT-Sr group were significantly higher than others, whereas trabecular separation decreased. CONCLUSIONS: These results indicated that an MNT-Sr surface promotes the differentiation of hBMMSCs in vitro and enhances bone-implant osseointegration in vivo, which may be a promising option for clinical implants in osteoporotic patients.

Development of tensile strength methodology for murine skin wound healing.

In this study, a methodology was evaluated and improved to quickly measure the tensile strength of murine skin in a biomechanical assay for an incisional wound healing model. The aim was to streamline and enhance the wound model, skin specimen preparation, and tensile test so that large numbers of fresh tissue could be tested reliably and rapidly. Linear incisions of 25-mm length were made in the dorsal skin of mice along the spine and metallic staples were used to close the wound. After 20 days, the mice were sacrificed, and a square-shaped section of skin containing the linear incision was excised. Two metallic punches were fabricated and used to punch 15-mm long strips of skin of 2 mm width whose length was orthogonal to the direction of incision. The tensiometer configuration was modified to expedite tensile measurements on fresh skin, and load-to-failure was measured for each strip of skin from the cephalad to the caudal region. We evaluated sources of error in the animal model and the testing protocol and developed procedures to maximize speed and reproducibility in tensile strength measurements. This report provides guidance for efficient and reproducible tensile strength measurement of large numbers of skin specimens from freshly sacrificed animals. •Tattoo placement to identify the two ends of the healing incisional wound assisted in decreasing error in the position and orientation of tensile strips.•Custom-made punches to prepare skin strips for tensile testing helped conduct tensile tests of fresh tissue rapidly.•Alteration of the manual grips of the tensile tester enabled specimens to be gripped rapidly to significantly accelerate testing for each skin strip.

Material properties of ultra-high molecular weight polyethylene: Comparison of tension, compression, nanomechanics and microstructure across clinical formulations.

This is the first study to simultaneously measure material properties in tension, compression, nanoindentation as well as microstructure (crystallinity and lamellar level properties) across a wide variety of clinically relevant ultra-high molecular weight polyethylene (UHMWPE) formulations. Methodologies for the measurement of UHMWPE mechanical properties-namely elastic modulus, yield stress, yield strain, ultimate strength, energetic toughness, Poisson's ratio, hardness and constitutive variables-are evaluated. Engineering stress-strain behavior is compared to true stress-strain behavior for UHMWPE across a range of cross-linking and antioxidant chemistry. The tensile mechanical properties and constitutive behavior of UHMWPE are affected by resin type, antioxidant source and degree of cross-linking. Poisson's ratio is shown to be affected by resin type, antioxidant addition, and cross-linking dosage. Relationships between bulk mechanical properties from different measurement methodologies as well as microstructure are analyzed across all material formulations using Spearman rank correlation coefficients. Modulus and yield strength correlate in both tension and compression. Similarly, tensile and compressive properties including modulus and yield strength correlate strongly with crystallinity (Xc) and lamellar thickness (D). This work has broad application and provides a basis for interpreting the mechanical behavior of UHMWPE used in orthopedic implants.

Ultra-High Molecular Weight Polyethylene: Influence of the Chemical, Physical and Mechanical Properties on the Wear Behavior. A Review.

Ultra-high molecular weight polyethylene (UHMWPE) is the most common bearing material in total joint arthroplasty due to its unique combination of superior mechanical properties and wear resistance over other polymers. A great deal of research in recent decades has focused on further improving its performances, in order to provide durable implants in young and active patients. From "historical", gamma-air sterilized polyethylenes, to the so-called first and second generation of highly crosslinked materials, a variety of different formulations have progressively appeared in the market. This paper reviews the structure-properties relationship of these materials, with a particular emphasis on the in vitro and in vivo wear performances, through an analysis of the existing literature.

Osteogenic activity of titanium surfaces with hierarchical micro-/nano-structures obtained by hydrofluoric acid treatment.

An easier method for constructing the hierarchical micro-/nano-structures on the surface of dental implants in the clinic is needed. In this study, three different titanium surfaces with microscale grooves (width 0.5-1, 1-1.5, and 1.5-2 µm) and nanoscale nanoparticles (diameter 20-30, 30-50, and 50-100 nm, respectively) were obtained by treatment with different concentrations of hydrofluoric acid (HF) and at different etching times (1%, 3 min; 0.5%, 12 min; and 1.5%, 12 min, respectively; denoted as groups HF1, HF2, and HF3). The biological response to the three different titanium surfaces was evaluated by in vitro human bone marrow-derived mesenchymal stem cell (hBMMSC) experiments and in vivo animal experiments. The results showed that cell adhesion, proliferation, alkaline phosphatase activity, and mineralization of hBMMSCs were increased in the HF3 group. After the different surface implants were inserted into the distal femurs of 40 rats, the bone-implant contact in groups HF1, HF2, and HF3 was 33.17%±2.2%, 33.82%±3.42%, and 41.04%±3.08%, respectively. Moreover, the maximal pullout force in groups HF1, HF2, and HF3 was 57.92±2.88, 57.83±4.09, and 67.44±6.14 N, respectively. The results showed that group HF3 with large micron grooves (1.5-2.0 µm) and large nanoparticles (50-100 nm) showed the best bio-functionality for the hBMMSC response and osseointegration in animal experiments compared with other groups.

The Effect of Hierarchical Micro/Nanotextured Titanium Implants on Osseointegration Immediately After Tooth Extraction in Beagle Dogs.

BACKGROUND: Owing to simplify the operation and shorten the overall duration of treatment, immediate implantation earned much satisfactory from patients and dentists. The results of immediate implantation determined by osseointegration, we fabricated a micro/nanotextured titanium implants to improve osseointegration immediately after tooth extraction. PURPOSE: The aim of this study was to investigate the effect of hierarchical micro/nanotextured titanium implant on osseointegration immediately after tooth extraction. MATERIAL AND METHODS: The micro/nanotextured titanium implants were fabricated by etching with 0.5 wt% hydrofluoric (HF) acid followed by anodization in HF electrolytes. Implants with a machined surface as well as implants a microtextured surface prepared by 0.5 wt% HF etching served as control groups. The machined, microtextured, and micro/nanotextured implants were inserted into fresh sockets immediately after tooth extraction in beagle dogs. Twelve weeks after implantation, the animals were sacrificed for micro-CT scanning, histological analysis and biomechanical test. RESULTS: The micro-CT imaging revealed that the bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) in the micro/nanotextured group was significantly higher than that in the machined group and microtextured group, and the trabecular separation (Tb.Sp) in the micro/nanotextured group was significantly lower than that in the other groups. For the histological analysis, the bone-to-implant contact in the machined, micro and micro/nanotextured groups were 47.13 ± 6.2%, 54.29 ± 4.18%, and 63.38 ± 7.63%, respectively, and the differences significant. The maximum pull-out force in the machined, micro, and micro/nanotextured groups were 216.58 ± 38.71 N, 259.42 ± 28.93 N, and 284.73 ± 47.09 N, respectively. CONCLUSIONS: The results indicated that implants with a hierarchical micro/nanotextured can promote osseointegration immediately after tooth extraction.

J-integral fracture toughness, Tearing modulus and tensile properties of Vitamin E stabilized radiation crosslinked UHMWPE.

Radiation crosslinking of ultra-high molecular weight polyethylene (UHMWPE) increases its wear resistance in total joint replacement prostheses. Unfortunately, it is accompanied by a dose-dependent decrease in several mechanical properties. In this study, the tensile properties and fracture behavior of radiation crosslinked, Vitamin E stabilized UHMWPE was studied as a function of radiation dose. The Rice and Sorensen model, applicable to elastic-plastic materials, was utilized to obtain the initial crack driving force, J1c, steady state J-integral fracture toughness, Jss and the Tearing modulus. Tensile tests showed the dependence of tensile properties on radiation dose. Jss of non-crosslinked UHMWPE was higher than for crosslinked UHMWPE׳s but there was no dose dependent change in Jss whereas there was almost no change in J1c over the entire dose range. Finally, a monotonic decrease in Tearing modulus was observed with radiation dose.

A comparison of the efficacy of various antioxidants on the oxidative stability of irradiated polyethylene.

BACKGROUND: Ultrahigh-molecular-weight polyethylene (UHMWPE) is subjected to radiation crosslinking to form highly crosslinked polyethylene (HXLPE), which has improved wear resistance. First-generation HXLPE was subjected to thermal treatment to reduce or quench free radicals that can induce long-term oxidative degeneration. Most recently, antioxidants have been added to HXLPE to induce oxidative resistance rather than by thermal treatment. However, antioxidants can interfere with the efficiency of radiation crosslinking. QUESTIONS/PURPOSES: We sought to identify (1) which antioxidant from among those tested (vitamin E, ß-carotene, butylated hydroxytoluene, or pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate]) causes the least reduction of crosslinking; (2) which promotes the greatest oxidative stability; and (3) which had the lowest ratio of oxidation index to crosslink density. METHODS: Medical-grade polyethylene (PE) resin was blended with 0.1 weight % of the following stabilizers: alpha tocopherol (vitamin E), ß-carotene, butylated hydroxytoluene (BHT), and pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate] (a hindered phenol antioxidant [HPAO]). These blends were compression-molded into sheets and subjected to electron beam irradiation to a dose of 100 kGy. Equilibrium swelling experiments were conducted to calculate crosslink density. Each PE was subjected to accelerated aging for a period of 2 weeks and Fourier transform infrared spectroscopy was used to measure the maximum oxidation. Statistical analysis was conducted using analysis of variance with Fisher's protected least significant difference in which a p value of < 0.05 was used to define a significant difference. RESULTS: The least reduction of crosslinking in antioxidant-containing HXLPE was observed with HPAO, which had a crosslink density (n = 6) of 0.167 (effect size [ES] = 0.87; 95% confidence interval [CI], 0.162-0.173) mol/dm(3) compared with 0.139 (ES = 1.57; 95% CI, 0.132-0.146) mol/dm(3) (p = 0.020) for BHT, 0.131 (ES = 1.77; 95% CI, 0.123-0.139) mol/dm(3) (p = 0.004) for ß-carotene, and 0.130 (ES = 1.79; 95% CI, 0.124-0.136) mol/dm(3) (p = 0.003) for vitamin E, whereas pure HXLPE had a crosslink density of 0.203 (95% CI, 0.170-0.235) mol/dm(3) (p = 0.005). BHT-PE had an oxidation index of 0.21 (ES = 13.14; 95% CI, 0.19-0.22) followed by HPAO-PE, vitamin E-PE and ß-carotene-PE, which had oxidation indices of 0.28 (ES = 9.68; 95% CI, 0.28-0.29), 0.29 (ES = 9.59; 95% CI, 0.27-0.30), and 0.35 (ES = 6.68; 95% CI, 0.34-0.37), respectively (p < 0.001 for all groups). BHT-PE had the lowest ratio of oxidation index to crosslink density of the materials tested (1.49, ES = 1.94; 95% CI, 1.32-1.66) followed by HPAO-PE (1.70, ES = 1.52; 95% CI, 1.61-1.80), vitamin E-PE (2.21, ES = 0.52; 95% CI, 2.05-2.38), and ß-carotene-PE (2.69, ES = -0.43; 95% CI, 2.46-2.93) compared with control PE (2.47, 95% CI, 2.07-2.88) with ß-carotene (p = 0.208) and vitamin E (p = 0.129) not being different from the control. CONCLUSIONS: BHT-modified HXLPE was found in this study to have the lowest oxidation index as well as the lowest ratio of oxidation index to crosslink density compared with vitamin E, HPAO, and ß-carotene-modified HXLPEs. More comprehensive studies are required such as wear testing using joint simulators as well as biocompatibility studies before BHT-modified HXLPE can be considered for clinical use. CLINICAL RELEVANCE: BHT is a synthetic antioxidant commonly used in the polymer industry to prevent long-term oxidative degradation and has been approved by the FDA for use in cosmetics and foodstuffs. It may be an attractive potential stabilizer for HXLPE in total joint replacements.

The relative effects of radiation crosslinking and type of counterface on the wear resistance of ultrahigh-molecular-weight polyethylene.

The lifetime of total joint replacement prostheses utilizing ultrahigh-molecular-weight polyethylene (UHMWPE) components has historically been determined by their wear resistance. It has been discovered that radiation crosslinking of UHMWPE can substantially increase its wear resistance. However, it is also well recognized that there is a radiation-dose-dependent decrease in several important mechanical properties of UHMWPE, such as fracture toughness and resistance to fatigue crack propagation. In this study, the effect of radiation crosslinking (followed by remelting) on the morphology, tensile properties and wear resistance of UHMWPE was investigated. Wear tests were conducted against both the commonly used cobalt-chromium counterface polished to implant grade smoothness as well as a smoother ceramic (alumina) counterface. The results showed that 50kGy dose radiation crosslinking increased the wear resistance of UHMWPE against the cobalt-chromium counterface 7-fold, but the coupling of remelted, crosslinked UHMWPE against the smoother alumina counterface led to a 20-fold increase in wear resistance. This study shows that the use of an alumina counterface would circumvent the need to use a high radiation dose in crosslinking UHMWPE, associated with poor mechanical properties, without compromising wear resistance.

Tensile and tribological properties of high-crystallinity radiation crosslinked UHMWPE.

Osteolysis due to particulate wear debris associated with ultrahigh molecular weight polyethylene (UHMWPE) components of total joint replacement prostheses has been a major factor determining their in vivo lifetime. In recent years, radiation crosslinking has been employed to decrease wear rates in PE components, especially in acetabular cups of total hip replacement prostheses. A drawback of radiation crosslinking is that it leads to a crosslinked PE (or XPE) with lower mechanical properties compared with uncrosslinked PE. In contrast, high-crystallinity PEs are known to have several mechanical properties higher than conventional PE. In this study, we hypothesized that increasing the crystallinity of radiation crosslinked and remelted XPE would result in an increase in tensile properties without compromising wear resistance. High-pressure crystallization was performed on PE and XPE and analyzed for the resulting morphological alterations using differential scanning calorimeter, low voltage scanning electron microscopy, and ultrasmall angle X-ray scattering. Uniaxial tensile tests showed that high-pressure crystallization increased the tensile modulus and yield stress in both PE and XPE, decreased the ultimate strain and ultimate stress in PE but had no significant effect on ultimate strain or ultimate stress in XPE. Multidirectional wear tests demonstrated that high-pressure crystallization decreased the wear resistance of PE but had no effect on the wear resistance of XPE. In conclusion, this study shows that high-pressure crystallization can be effectively used to increase the crystallinity and modulus of XPE without compromising its superior wear resistance compared with PE.

Nanoparticulate fillers improve the mechanical strength of bone cement.

BACKGROUND AND PURPOSE: Polymethylmethacrylate (PMMA-) based bone cement contains micrometer-size barium sulfate or zirconium oxide particles to radiopacify the cement for radiographic monitoring during follow-up. Considerable effort has been expended to improve the mechanical qualities of cements, largely through substitution of PMMA with new chemical structures. The introduction of these materials into clinical practice has been complicated by concerns over the unknown long-term risk profile of these new structures in vivo. We investigated a new composite with the well characterized chemical composition of current cements, but with nanoparticles instead of the conventional, micrometer-size barium sulfate radiopacifier. METHODS: In this study, we replaced the barium sulfate microparticles that are usually present in commercial PMMA cements with barium sulfate nanoparticles. The resultant "microcomposite" and "nanocomposite" cements were then characterized through morphological investigations such as ultra-small angle X-ray scattering (USAXS) and scanning electron microscopy (SEM). Mechanical characterization included compression, tensile, compact tension, and fatigue testing. RESULTS: SEM and USAXS showed excellent dispersion of nanoparticles. Substitution of nanoparticles for microparticles resulted in a 41% increase in tensile strain-to-failure (p = 0.002) and a 70% increase in tensile work-of-fracture (p = 0.005). The nanocomposite cement also showed a two-fold increase in fatigue life compared to the conventional, microcomposite cement. INTERPRETATION: In summary, nanoparticulate substitution of radiopacifiers substantially improved the in vitro mechanical properties of PMMA bone cement without changing the known chemical composition.

The combined effects of crosslinking and high crystallinity on the microstructural and mechanical properties of ultra high molecular weight polyethylene.

Ultra high molecular weight polyethylene (PE) has been used for more than forty years as the bearing surface in total joint replacements. In recent years, there have been numerous advances in processing conditions that have improved the wear resistance of this material. In particular, crosslinking has been shown to dramatically improve the wear behavior of this orthopedic polymer in simulator studies. This benefit to wear resistance, however, is accompanied by a decrease in mechanical properties such as ultimate tensile strength, ductility, toughness and fatigue resistance. This degradation to mechanical properties may have serious implications for devices with high stress concentrations or large cyclic contact stresses. Tailoring microstructure for improved structural performance is essential for implant design. In this work we examined the role of crystallinity and crosslinking on the microstructure and mechanical properties of PE. Crystallinity was increased with a high pressure process and crosslinking was obtained with gamma irradiation. Crystallinity was beneficial to fatigue crack propagation resistance and when coupled with crosslinking a polymer with both wear and fatigue resistance was obtained.

Wear reduction of orthopaedic bearing surfaces using polyelectrolyte multilayer nanocoatings.

This work explores the use of conformal polyelectrolyte multilayer (PEM) coatings for wear reduction of orthopedic bearing surfaces. These films, with easily tunable architectures, provide excellent adhesion to a wide variety of metallic, plastic, and ceramic substrates. For this study, PEM films, only a few hundred nanometers thick, were assembled by sequential adsorption of poly(acrylic acid) and poly(allylamine hydrochloride). It was observed that the pH of the polylectrolyte solutions used for film assembly needs careful consideration to avoid any adverse effects on film structure when exposed to physiological conditions of pH and ionic strength. The wear reducing capacity of these coatings in the presence of bovine calf serum-lubricant solution was established for metal/metal systems at the meso/microscale over 30 cycles of reciprocating motion, as well as for the commonly used metal/ultra-high molecular weight polyethylene (UHMWPE) system over 500,000 cycles of bi-directional motion in a macroscale pin-on-disk test. In the latter case, the use of the films reduced UHMWPE wear by up to 33% when compared with the uncoated control. This is the first clinically relevant laboratory demonstration of the wear-reducing ability of these films. Further optimization will be needed before this novel class of materials can be used by the orthopedic community.

A study of the nanostructure and tensile properties of ultra-high molecular weight polyethylene.

Ultra-high molecular weight polyethylene (UHMWPE) has gained worldwide acceptance as a bearing material used in orthopaedic implants. Despite its widespread use, inherent properties of the polymer continue to limit the wear resistance and the clinical lifespan of implanted knee and hip prosthetics containing UHMWPE components. The degree of crystallinity of UHMWPE is known to strongly influence several of its tensile mechanical properties such as Young's modulus, yield stress, strain-hardening rates, work of fracture and ultimate tensile properties. In this study, medical grade UHMWPE was subjected to four different crystallization conditions resulting in UHMWPE with a range of crystalline morphologies. Thereafter, the crystalline nanostructure was quantitatively characterized using a combination of ultra-small angle X-ray scattering and differential scanning calorimetry. Low-voltage scanning electron microscopy was employed as a supplementary technique to compare the crystalline morphology resulting from each crystallization condition. In addition, uniaxial tensile tests were performed to assess the effects of crystallization conditions on the mechanical properties of UHMWPE. This study showed that while crystallization conditions strongly influenced the morphology of UHMWPE, in most cases the mechanical properties of the material were not significantly affected.