Development and therapeutic applications of advanced biomaterials

Millions of patients worldwide have benefited from technological innovation from biomaterials. Yet, while life expectancy continues to increase, organ failure and traumatic injury continue to fill hospitals and diminish the quality of life. Advances in understanding disease and tissue regeneration combined with increased accessibility of modern technology have created new opportunities for the use of biomaterials in unprecedented ways. Materials can now be rapidly created and selected to target specific cells, change shape in response to external stimulus, and instruct tissue regeneration. Here we describe a few of these technologies with emphasis on targeted drug delivery vehicles, high-throughput material synthesis, minimally invasive biodegradable shape-memory materials, and development of strategies to enhance tissue regeneration through delivery of instructive materials.     

Simulation of fretting wear at orthopaedic implant interfaces

Osteolysis due to wear debris is a primary cause of failure of total joint replacements. Although debris produced by the joint articulating surfaces has been studied and simulated extensively, fretting wear debris, produced at nonarticulating surfaces, has not received adequate attention. We developed a three-station fretting wear simulator to reproduce in vivo motion and stresses at the interfaces of total joint replacements. The simulator is based on the beam bending theory and is capable of producing cyclic displacement from 3 to 1000 microns, under varying magnitudes of contact stresses. The simulator offers three potential advantages over previous studies: The ability to control the displacement by load, the ability to produce very small displacements, and dynamic normal loads as opposed to static. A pilot study was designed to test the functionality of the simulator, and verify that calculated displacements and loads produced the predicted differences between two commonly used porous ingrowth titanium alloy surfaces fretting against cortical bone. After 1.5 million cycles, the simulator functioned as designed, producing greater wear of bone against the rougher plasma-sprayed surface compared to the fiber-mesh surface, as predicted. A novel pin-on-disk apparatus for simulating fretting wear at orthopaedic implant interfaces due to micromotion is introduced. The test parameters measured with the fretting wear simulator were as predicted by design calculations, and were sufficient to measure differences in the height and weight of cortical bone pins rubbing against two porous ingrowth surfaces, plasma-sprayed titanium and titanium fiber mesh.     

Force and torque modelling of drilling simulation for orthopaedic surgery

The advent of haptic simulation systems for orthopaedic surgery procedures has provided surgeons with an excellent tool for training and preoperative planning purposes. This is especially true for procedures involving the drilling of bone, which require a great amount of adroitness and experience due to difficulties arising from vibration and drill bit breakage. One of the potential difficulties with the drilling of bone is the lack of consistent material evacuation from the drill's flutes as the material tends to clog. This clogging leads to significant increases in force and torque experienced by the surgeon. Clogging was observed for feed rates greater than 0.5 mm/s and spindle speeds less than 2500 rpm. The drilling simulation systems that have been created to date do not address the issue of drill flute clogging. This paper presents force and torque prediction models that account for this phenomenon. The two coefficients of friction required by these models were determined via a set of calibration experiments. The accuracy of both models was evaluated by an additional set of validation experiments resulting in average R² regression correlation values of 0.9546 and 0.9209 for the force and torque prediction models, respectively. The resulting models can be adopted by haptic simulation systems to provide a more realistic tactile output.     

Revolutionizing orthopaedic biomaterials: The potential of biodegradable and bioresorbable magnesium-based materials for functional tissue engineering

In recent years, there has been a surge of interest in magnesium (Mg) and its alloys as biomaterials for orthopaedic applications, as they possess desirable mechanical properties, good biocompatibility, and biodegradability. Also shown to be osteoinductive, Mg-based materials could be particularly advantageous in functional tissue engineering to improve healing and serve as scaffolds for delivery of drugs, cells, and cytokines. In this paper, we will present two examples of Mg-based orthopaedic devices: an interference screw to accelerate ACL graft healing and a ring to aid in the healing of an injured ACL.     

Total hip arthroplasty wear simulation using the boundary element method

In this paper an application of the boundary element method for simulating wear in total hip prosthesis is presented. Several examples including different update periods of the worn acetabular cup, various femoral head sizes and various materials for both the femoral head and the acetabular cup are simulated under the same variable loading conditions for up to 20 years of service. Moreover, two different femoral models are considered in order to investigate the influence of the femoral modelling. The analysis demonstrates that due to the boundary only modelling requirement, the computational time and storage remains low, allowing large service periods to be simulated. Generally, the results obtained are in good agreement with other researchers findings. Moreover, ignoring the bending of the femoral neck in the model, results in a small overestimation of the maximum wear depth, while the volumetric wear is slightly underestimated. However, these differences are trivial considering the reduction of the computational effort.     

In vitro wear simulation on the RandomPOD wear testing system as a screening method for bearing materials intended for total knee arthroplasty

The 16-station RandomPOD wear test system, previously validated for prosthetic hip wear, was used in the simulation of knee wear mechanisms with a ball-on-flat test configuration. This consisted of a CoCr pin with a ground and polished spherical bearing surface (radius 28 mm) against a conventional, gamma-sterilized UHMWPE disk in serum lubrication. The biaxial motion, consisting of x and y translations, and the load was non-cyclic. Relative to the disk, the center of contact wandered within a circle of 10 mm diameter, and the average sliding velocity was 15.5 mm/s (ranging from 0 to 31 mm/s). The load varied non-cyclically between 0 and 142 N (average 73 N). In the 60-day test with 16 similar wear couples, moderate adhesive wear, the principal wear mechanism of a well-functioning prosthetic knee, dominated. This showed as a burnished, circular wear mark (diameter 13.2 mm, area 137 mm²). The wear factor was 2.04±0.03×10⁻⁶ mm³/N m (mean±95 percent confidence limit). For the first time a truly multidirectional, realistic and uniform, large capacity pin-on-disk simulation of knee wear mechanisms was implemented.     

Tracing cellulose elements adsorbed on composite cellulose biomaterials by a new labeling method

In view of tracing the fate of cellulose fine elements added to a suspension of cellulose fibers, a novel method for specific labeling of polysaccharides in a composite material was developed. The purpose was to visualize a given cellulose material within a cellulose mixture. The method consists of generating aldehyde groups in the chain by mild periodic acid oxidation followed by biotinylation of the carbonyls. Once added to the composite, the biotinylated molecules are labeled with streptavidin conjugated to a fluorescent probe for confocal microscopy, or streptavidin-gold for electron microscopy observations. In the present work, the fate of fresh fines (never-dried) and dead fines (dried) when they were added to a purified suspension of fibers was followed by observation of the labeling in confocal and electron microscopy. The differential mode of interaction of fresh fines and dead fines with the fibers was correlated to the mechanical characteristics measured on the corresponding papers. The versatility of the new labeling method and its possible generalization to other polysaccharides incorporated to a polysaccharide or nonpolysaccharide material should be of potential interest for the study of composite microstructure.     

A new method for finite element simulation of orthodontic appliance-teeth-periodontium-alveolus system

This paper describes a new simulation method to analyze the initial behavior of the total system comprising orthodontic appliance, teeth, and their supporting structures. It is based on a finite element method which additionally takes account of a rotational degree of freedom. Beam and rod elements are used for finite element idealization of orthodontic appliance. Through spring elements it is connected with the teeth supported by the alveolar structures. The technique of 'initial strain' is introduced so as to analyze the effects of a gable bend and activation on the force system which is delivered by the orthodontic appliance. As compared with the photoelastic technique hitherto used, this method serves to investigate systematically and quantitatively the initial aspect of orthodontic tooth movement.     

Prodrugs as self-assembled hydrogels: a new paradigm for biomaterials

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Highlights► Development of prodrug-based self-assembled hydrogels as a new class of biomaterials. ► Design of prodrugs that can self-assemble to form hydrogels. ► These hydrogels overcome limitations such as low-drug loading and burst release of drugs. ► Locally injectable self-assembled hydrogels exhibit potential as effective therapeutics.     

Fungal laccases as tools for the synthesis of new hybrid molecules and biomaterials

Laccase is a ligninolytic enzyme widely distributed in wood-rotting fungi and which is also found in a variety of molds and insects as well as some plants and bacteria. Its biological roles range from depolmerization of lignin, coal and humic acids via the oxidation of various mono- and diaromatic structures, to polymerization reactions and pigment formation in microbial cells or spores. Apart from its action in catabolic, depolymerizing and polymerizing processes, laccases have also been shown to be powerful enzymes for coupling two different molecules to create new low-molecular-weight products in high yield. In addition to their homomolecular coupling capabilities, laccases are also able to couple a hydroxylated aromatic substrate with a nonlaccase substrate of variable structure to create new heteromolecular hybrid molecules. Thus, laccases are increasingly finding applications in biotechnology in the fields of environment-friendly synthesis of fine chemicals and for the gentle derivatization of biologically active compounds e.g., antibiotics, amino acids, antioxidants, and cytostatics. Finally, oligomerization and polymerization reactions can lead to new homo- or heteropolymers and biomaterials. These may be useful in a wide range of applications including the production of polymers with antioxidative properties, the copolymerizing of lignin components with low-molecular mass compounds, the coating of cellulosic cotton fibers or wool, the coloring of hair and leathers, or the cross-linking and oligomerization of peptides.     

Cryobanking of viable biomaterials: implementation of new strategies for conservation purposes

Cryobanking, the freezing of biological specimens to maintain their integrity for a variety of anticipated and unanticipated uses, offers unique opportunities to advance the basic knowledge of biological systems and their evolution. Notably, cryobanking provides a crucial opportunity to support conservation efforts for endangered species. Historically, cryobanking has been developed mostly in response to human economic and medical needs — these needs must now be extended to biodiversity conservation. Reproduction technologies utilizing cryobanked gametes, embryos and somatic cells are already vital components of endangered species recovery efforts. Advances in modern biological research (e.g. stem cell research, genomics and proteomics) are already drawing heavily on cryobanked specimens, and future needs are anticipated to be immense. The challenges of developing and applying cryobanking for a broader diversity of species were addressed at an international conference held at Trier University (Germany) in June 2008. However, the magnitude of the potential benefits of cryobanking stood in stark contrast to the lack of substantial resources available for this area of strategic interest for biological science — and society at large. The meeting at Trier established a foundation for a strong global incentive to cryobank threatened species. The establishment of an Amphibian Ark cryobanking programme offers the first opportunity for global cooperation to achieve the cryobanking of the threatened species from an entire vertebrate class.     

Numerical simulation of fibrous biomaterials with randomly distributed fiber network structure

This paper presents a computational framework to simulate the mechanical behavior of fibrous biomaterials with randomly distributed fiber networks. A random walk algorithm is implemented to generate the synthetic fiber network in 2D used in simulations. The embedded fiber approach is then adopted to model the fibers as embedded truss elements in the ground matrix, which is essentially equivalent to the affine fiber kinematics. The fiber–matrix interaction is partially considered in the sense that the two material components deform together, but no relative movement is considered. A variational approach is carried out to derive the element residual and stiffness matrices for finite element method (FEM), in which material and geometric nonlinearities are both included. Using a data structure proposed to record the network geometric information, the fiber network is directly incorporated into the FEM simulation without significantly increasing the computational cost. A mesh sensitivity analysis is conducted to show the influence of mesh size on various simulation results. The proposed method can be easily combined with Monte Carlo (MC) simulations to include the influence of the stochastic nature of the network and capture the material behavior in an average sense. The computational framework proposed in this work goes midway between homogenizing the fiber network into the surrounding matrix and accounting for the fully coupled fiber–matrix interaction at the segment length scale, and can be used to study the connection between the microscopic structure and the macro-mechanical behavior of fibrous biomaterials with a reasonable computational cost.     

A new device and method for rapid processing of cytologic smears, histologic sections and cell cultures for electron microscopy

A device and technique are described by means of which samples may be selectively lifted from flat surfaces, such as microscope slides or coverslips, and processed for examination with the electron microscope. The device consists of a spring clamp that holds the narrow end of an open-tipped, conical B.E.E.M. or similar capsule sealed against the surface from which the sample of interest is to be removed. All processing of the sample for electron microscopy can take place within the capsule. When completed, the capsule filled with solidified resin is removed with the area of interest of the sample embedded in its tip.