Modeling of peptide adsorption interactions with a poly(lactic acid) surface.

The biocompatibility of implanted materials and devices is governed by the conformation, orientation, and composition of the layer of proteins that adsorb to the surface of the material immediately upon implantation, so an understanding of this adsorbed protein layer is essential to the rigorous and methodical design of implant materials. In this study, novel molecular dynamics techniques were employed in order to determine the change in free energy for the adsorption of a solvated nine-residue peptide (GGGG-K-GGGG) to a crystalline polylactide surface in an effort to elucidate the fundamental mechanisms that govern protein adsorption. This system, like many others, involves two distinct types of sampling problems: a spatial sampling problem, which arises due to entropic effects creating barriers in the free energy profile, and a conformational sampling problem, which occurs due to barriers in the potential energy landscape. In a two-step process that addresses each sampling problem in turn, the technique of biased replica exchange molecular dynamics was refined and applied in order to overcome these sampling problems and, using the information available at the atomic level of detail afforded by molecular simulation, both quantify and characterize the interactions between the peptide and a relevant biomaterial surface. The results from these simulations predict a fairly strong adsorption response with an adsorption free energy of -2.5 +/- 0.6 kcal/mol (mean +/- 95% confidence interval), with adsorption primarily due to hydrophobic interactions between the nonpolar groups of the peptide and the PLA surface. As part of a larger and ongoing effort involving both simulation and experimental investigations, this work contributes to the goal of transforming the engineering of biomaterials from one dominated by trial-and-error to one which is guided by an atomic-level understanding of the interactions that occur at the tissue-biomaterial interface.

Femoral strain profiles under simulated 3-D muscle and joint loads for heel strike, midstance, and toe off.

A universal static hip joint simulation apparatus was designed to simulate both 3-D joint and 3-D muscle forces for each of the three load-bearing phases of normal gait. The adjustability provided by the apparatus allowed for the consideration of femoral orientation, hip joint contact force, and primary active muscle loads for each simulated activity. Use of this apparatus enables the biomechanical response of the femur to be more fully and accurately determined under a full range of everyday activities. Results demonstrate that the proximal femur experiences significantly higher levels of strain during the activities of toe off and heel strike than during midstance. This evaluation underscores the importance of considering each phase of gait when investigating the biomechanical response of the femur, which should be especially relevant in the design and evaluation of femoral components for hip joint arthroplasty. Future studies are planned for femoral strain evaluation following simulated hip joint replacement. By providing a more complete strain profile evaluation of the femur as a function of implant design, the use of this apparatus should contribute to the development of new femoral component designs for improved patient care.

Structural response and relative strength of a laminated composite hip prosthesis: effects of functional activity.

To obtain a better appreciation for the structural performance of a laminated composite hip prosthesis (CP), we examined in situ prosthesis structural response and relative strengths as a function of walking and stair climbing using our previously developed analysis guidelines. Accordingly, we examined overall prosthesis structural response utilizing a global continuum level modeling approach and prosthesis relative strengths using a local microstructural (or ply-level) modeling approach. As a reference and control, we examined the structural performance of the intact natural femur (NAT) and a titanium alloy (Ti) based hip prosthesis. In terms of the overall structural response, i.e., the femur/prosthesis deformational response, stem/bone interfacial stress transfer, and calcar strain energy density restored, the performance of the CP prosthesis was moderately improved over that of the control Ti prosthesis and better approximates the NAT response. In terms of relative strength, we found that the neck of the CP prosthesis failed for all activities with the exception of the mid-stance phase of level walking. However, the prosthesis appears to have sufficient relative strength for function at positions distal to the neck of the prosthesis. While these results dampen enthusiasm for consideration of laminated composite hip prostheses designed with a shape based on a metal alloy implant, they indirectly support consideration of alternate hip prosthesis structural designs such as using a better supported prosthesis neck or utilizing metal/composite hybrid constructions. Importantly, our simulation and analysis approach could be utilized in the design of other laminated composite biomedical structural components.

Determination of apparent thermodynamic parameters for adsorption of a midchain peptidyl residue onto a glass surface.

Protein adsorption onto the surface of an implanted material is widely recognized as an important factor controlling the biological response. Although numerous studies have been conducted to investigate protein adsorption behavior, very little is actually understood regarding the specific molecular events involved in protein-surface adsorption processes. As a basic science approach to investigate protein-surface interactions, an experimental method is developed and applied to determine apparent thermodynamic parameters for the adsorption of a single midchain peptidyl residue onto a glass surface. This article presents the results of adsorption studies for four molecular weight ranges of poly-L-lysine onto glass microspheres in physiologic saline at four temperatures. Isotherm data plots are constructed and the apparent changes in enthalpy (DeltaH degrees ), entropy (DeltaS degrees ), and Gibbs' free energy (DeltaG degrees ) are calculated assuming a Langmuir-like model for adsorption. Estimates of apparent DeltaH degrees, DeltaS degrees, and DeltaG degrees for the adsorption of a single midchain lysine residue are determined from the initial slopes of the plots of the apparent thermodynamic parameters versus the degree of polymerization of the adsorbed poly-L-lysine. It is proposed that the generation of such molecular-level adsorption data is a necessary step toward the goal of understanding, predicting, and controlling protein-surface interactions.

Real-time dissolution measurement of sized and unsized calcium phosphate glass fibers.

The objective of this study was to develop an efficient "real time" measurement system able to directly measure, with microgram resolution, the dissolution rate of absorbable glass fibers, and utilize the system to evaluate the effectiveness of silane-based sizing as a means to delay the fiber dissolution process. The absorbable glass fiber used was calcium phosphate (CaP), with tetramethoxysilane selected as the sizing agent. E-glass fiber was used as a relatively nondegrading control. Both the unsized-CaP and sized-CaP degraded linearly at both the 37 degrees C and 60 degrees C test temperature levels used. No significant decrease in weight-loss rate was recorded when the CaP fiber tows were pretreated, using conventional application methods, with the tetramethoxysilane sizing for either temperature condition. The unsized-CaP and sized-CaP weight loss rates were each significantly higher at 60 than at 37 degrees C (both p < 0.02), as expected from dissolution kinetics. In terms of actual weight loss rate measured using our system for phosphate glass fiber, the unsized-CaP fiber we studied dissolved at a rate of 10.90 x 10(-09) and 41.20 x 10(-09) g/min-cm(2) at 37 degrees C and 60 degrees C, respectively. Considering performance validation of the developed system, the slope of the weight loss vs. time plot for the tested E-glass fiber was not significantly different compared to a slope equal to zero for both test temperatures.

Study of creep behavior of ultra-high-molecular-weight polyethylene systems.

The short- and long-term creep behaviors of ultra-high-molecular-weight polyethylene (UHMWPE) systems (compression-molded UHMWPE sheets and self-reinforced UHMWPE composites) have been investigated. The short-term (30-120 min) creep experiment was conducted at a load of 1 MPa and a temperature range of 37-62 degrees C. Based on short-term creep data, the long-term creep behavior of UHMWPE systems at 1 MPa and 37 degrees C was predicted using time-temperature superposition and analytical formulas. Compared to actual long-term creep experiments of up to 110 days, the predicted creep values were found to well describe the creep properties of the materials. The creep behaviors of the UHMWPE systems were then evaluated for a creep time of longer than 10 years, and it was found that most creep deformation occurs in the early periods. The shift factors associated with time-temperature superposition were found to increase with increasing temperature, as per the Arrhenius equation. The effects of temperature, materials, and load on the shift factors could be explained by the classical free volume theory.

Fixation of osteotomies using bioabsorbable screws in the canine femur.

The purpose of this study was to compare the healing properties of femoral osteotomies fixed by bioabsorbable screws (20:80 polyglycolic copolylactic acid copolymer) to standard stainless steel screws of a similar design in a dog femoral model. Two osteotomies were used, the trephine osteotomy (10 mm diameter) in the metaphyseal lateral femoral condyle and in the femoral diaphysis, and a unilateral osteotomy in the lateral femoral condyle. Two months after the trephine osteotomies, the femurs that contained the polymer screws were not significantly different in mechanical strength from the femurs treated with the stainless steel screws, either in the diaphyseal or metaphyseal model. There was no histological difference in bone healing between the metallic and polymer screws for all periods (2, 9, and 17 months). There was no adverse inflammatory response to the polymeric or metallic screws. By month 17, the polymer screws were resorbed completely. All the diaphyseal screw tracks had healed with bone and areas of remodeling were evident in two specimens. For the femoral condyle osteotomy model at 2 months, the polymer screws were present and intact, and all osteotomies healed with no evidence of inflammation. By 9 months, only one specimen had polymeric material left in the screw track. At 15 months, the screw tracks still were present but no evidence of any polymer remained. The tracks were filled with fibrous and adipose connective tissue. All osteotomies stabilized with either bioabsorbable polymer screws or stainless steel screws did heal satisfactorily without any complications, inflammation, or osteolysis. The polyglycolic polylactic acid copolymer may have a clinical role as a bioabsorbable material without the concerns for the osteolysis, foreign body reaction, and sterile abscess formation that have occurred with bioabsorbable fixation methods in the past.

Long-term compressive property durability of carbon fibre-reinforced polyetheretherketone composite in physiological saline.

In total hip arthroplasty, concerns such as corrosion and stress shielding associated with stiff metallic femoral components have led to the development of low stiffness advanced fibre-reinforced polymer (FRP) composite femoral components. Carbon fibre-reinforced polyetheretherketone (CF/PEEK) composite material is now one of the primary material systems being considered for composite hip stem development. As a hip stem, a composite material must be able to support a complex state of stress in the in vivo environment without failure. Considering the loading conditions of a hip stem (superimposed compression and bending), and the fact that FRP composites typically possess lower compressive than tensile strength, the compressive behaviour of FRP composites becomes very important for femoral component design. This paper presents an investigation of the long-term durability of 0 degree and 90 degrees compressive strengths of CF/PEEK composite following physiological saline saturation. 0 degree and 90 degrees compressive moduli and Poisson ratio (v12) properties are also reported. Samples were tested following conditioning in physiological saline at 37, 65 and 95 degrees C for time periods from 0 to 5000 h. Dry samples were tested as controls. Results show no significant loss in compressive property values of the saline-saturated or the dry control samples as a function of conditioning time or temperature.

Future materials for foot surgery.

Important advances have been made in the development of biomaterials science and engineering for foot surgery over the past four decades. In this paper, implant materials have been separated into two general categories: temporary implants for bone fixation and permanent implants for joint replacement. As presented, however, currently available temporary implants for bone fixation are often left in place permanently whereas, in the long run, permanent implants for joint replacement cannot realistically be expected to last the lifetime of the average-aged patient, and thus are actually only temporary. The benefits and problems of each of these two implant classes were first presented to set the stage for a discussion of possible future directions in the development of new biomaterials that offer the promise of providing improvements for patient care. For bone fixation in foot surgery, the most promising future biomaterials are presented as fully bioabsorbable polymer matrix composites. These implant materials have the potential for development to provide the initial strength and stiffness of currently used metal alloys without concern regarding implant removal. With the development of these materials, clinicians and patients will no longer be forced to choose between the risks of implant retrieval and the risks of leaving the implant behind. Current obstacles that must be overcome before these future materials can be introduced for general clinical use are related to improvements in mechanical property durability and degradation product biocompatibility. For joint replacement, tissue engineered viable biomaterials for permanent articular cartilage replacement are presented as the most important of the future biomaterials. If truly permanent joint replacement materials are to be developed, the implants must be able to regenerate and sustain themselves to permanently retain their properties. Living and sustainable tissues are therefore essential if implant properties are to be permanently maintained, because all nonviable materials are subject to eventual irreversible structural breakdown, degradation, and fatigue. Again, many problems remain to be solved before these envisioned future materials can be brought to accepted clinical use. However, substantial advances have already been achieved and have demonstrated the feasibility of the development of these materials. Biomaterials science and engineering remains a very challenging and exciting field of research and development. As technology advances, the problems that are faced become more complex and, more than ever, now require interdisciplinary cooperation from molecular and cell biologists, biomaterials scientists and engineers, and clinicians. This is especially true in the relatively new field of tissue engineering.(ABSTRACT TRUNCATED AT 400 WORDS)

Effectiveness of cleaning surgical implants: quantitative analysis of contaminant removal.

Surgical implants need to be free from contaminants before implantation. The effectiveness of a presently used Clemson bioengineering cleaning (CBC) protocol was evaluated for cleaning three different biomaterials (titanium, aluminum oxide, and polyethylene terephthalate, PET) contaminated with three different contaminants (calcium chloride, zinc chloride, and hexadecane). Radiolabeled tracer analysis (RTA), with the use of liquid scintillation, was used as the surface analytical technique to quantitatively determine the percent contaminant removed from the biomaterial surface. On average, the ultrasonic cleaning step removed 99.96% of all three contaminants from both titanium and aluminum oxide. The CBC protocol did not sufficiently clean PET fabric contaminated with hexadecane leaving 11.76% of the contaminant after the ultrasonic step. With the use of isopropyl alcohol in series with 1% Liquinox, the ultrasonic step cleaned the fabric soiled with hexadecane within 30 min, removing 99.85% of the hexadecane initially on the surface. RTA proved to be an excellent method of quantifying surface contamination on implant materials, and for assessing the effectiveness of cleaning protocols in question.

Long-term durability of the interface in FRP composites after exposure to simulated physiologic saline environments.

Fiber/matrix interfacial bond strength significantly influences the mechanical behavior of fiber-reinforced polymer (FRP) composites. Interfacial bond strength durability is therefore particularly important in the development of FRP composites for implant applications where diffused moisture may potentially weaken the material over time. In this study, the long-term durability of interfacial bonding in carbon fiber/380 grade polyetheretherketone (C/PEEK) and carbon fiber/polysulfone (C/PSF) composites was investigated after exposure to hygrothermal environments. A single fiber pull-out test was used to quantitatively determine the ultimate bond strength (UBS) of the samples following exposure. Samples were tested at three temperatures (37, 65, and 95 degrees C) for six time periods (0-5000 h) and in two environments (dry and physiologic saline-immersed). A mathematical model based on nth order chemical reaction kinetics was applied to describe the long-term durability of the interface. The results of this study indicate that interfacial bond strengths in C/PSF and C/PEEK (380 grade) composites are significantly decreased by exposure to physiologic saline and are functions of both time and temperature. For each material, the kinetics of degradation analysis predicts further bond strength losses following initial saturation, which then stabilizes at temperature-dependent equilibrium bond strength levels.

Development of FRP composite structural biomaterials: fatigue strength of the fiber/matrix interfacial bond in simulated in vivo environments.

Fiber/matrix interfacial bonding in fiber reinforced polymer (FRP) composite materials is potentially sensitive to degradation in aqueous environments. Ultimate bond strength (UBS) in carbon fiber/polysulfone (CF/PSF) and polyaramid/polysulfone (K49/PSF) was previously reported to be significantly decreased in two simulated in vivo environments. While UBS is a useful parameter, for orthopedic implant applications the fatigue behavior of the interface is probably a more relevant indicator of long-term composite material performance. In this article, the effects of simulated in vivo environments (saline, exudate) upon the fatigue behavior of the interface of CF/PSF and K49/PSF are reported. The fatigue behavior of both material combinations was linearly dependent on the logarithm of fatigue life in the dry (control), saline, and exudate environments. Testing either material in saline and exudate resulted in significantly lower fatigue strength than in the dry environment; however, results in the two wet environments were indistinguishable. The CF/PSF interface experienced fatigue failure at approximately 10(5) load cycles at a maximum applied load level of only 15% of its ultimate dry bond strength without indication of an endurance limit being reached. These results raise some important questions regarding the durability of CF/PSF composite in load bearing orthopedic applications.

Development of FRP composite structural biomaterials: ultimate strength of the fiber/matrix interfacial bond in in vivo simulated environments.

Fiber reinforced polymer (FRP) composites are being developed as alternatives to metals for structural orthopedic implant applications. FRP composite fracture behavior and environmental interactions are distinctly different from those which occur in metals. These differences must be accounted for in the design and evaluation of implant performance. Fiber/matrix interfacial bond strength in a FRP composite is known to strongly influence fracture behavior. The interfacial bond strength of four candidate fiber/matrix combinations (carbon fiber/polycarbonate, carbon fiber/polysulfone, polyaramid fiber/polycarbonate, polyaramid fiber/polysulfone) were investigated at 37 degrees C in dry and in vivo simulated (saline, exudate) environments. Ultimate bond strength was measured by a single fiber-microdroplet pull-out test. Dry bond strengths were significantly decreased following exposure to either saline or exudate with bond strength loss being approximately equal in both the saline and exudate. Bond strength loss is attributed to the diffusion of water and/or salt ions into the sample and their interaction with interfacial bonding. Because bond degradation is dependent upon diffusion, diffusional equilibrium must be obtained in composite test samples before the full effect of the test environment upon composite mechanical behavior can be determined.