Biocompatible liquid-crystal elastomers mimic the intervertebral disc.

The hierarchical and anisotropic mechanical behavior requirement of load-bearing soft tissues limits the utility of conventional elastomeric materials as a replacement for soft-tissue materials. Liquid-crystal elastomers (LCEs) have the potential to excel in this regard owing to its unique combination of mesogenic order in an elastomeric network. In this study, the mechanical behavior of the LCEs relevant to load-bearing biomedical applications was explored. LCEs with different network orientations (i.e., mesogen alignments) were investigated by fabricating the LCEs with polydomain and monodomain configurations. The polydomain and monodomain LCEs with the same degree of network crosslinking demonstrated diverse mechanical behavior, ranging from highly stiff and elastic nature to high damping capacity, depending on the loading direction with respect to the network alignment. The LCEs were also capable of matching the anisotropic mechanical behavior of an intervertebral disc. Additional studies were conducted on the in vivo biological response of LCEs upon subcutaneous implantation, as well as on the effect of the exposure to an in vitro simulated physiological environment on the mechanical behavior. The LCEs' mechanical response was negligibly affected when exposed to biomedically relevant conditions. Furthermore, the solid and porous LCEs did not show any adverse effect on the surrounding tissues when implanted subcutaneously in rats. The biological response allows for tissue ingrowth and helps illustrate their utility in implantable biological devices. Finally, the utility of LCEs to mimic the mechanical function of biological tissue such as intervertebral disc was demonstrated by fabricating a proof of concept total disc replacement device.

Cell Printing in Complex Hydrogel Scaffolds.

Advancements in the microfabrication of soft materials have enabled the creation of increasingly sophisticated functional synthetic tissue structures for a myriad of tissue engineering applications. A challenge facing the field is mimicking the complex microarchitecture necessary to recapitulate proper morphology and function of many endogenous tissue constructs. This paper describes the creation of PEGDA hydrogel microenvironments (microgels) that maintain a high level of viability at single cell patterning scales and can be integrated into composite scaffolds with tunable modulus. PEGDA was stereolithographically patterned using a digital micromirror device to print single cell microgels at progressively decreasing length scales. The effect of feature size on cell viability was assessed and inert gas purging was introduced to preserve viability. A composite PEGDA scaffold created by this technique was mechanically tested and found to enable dynamic adjustability of the modulus. Together this approach advances the ability to microfabricate tissues that better mimic native constructs on cellular and subcellular length scales.

Thermomechanical properties of monodomain nematic main-chain liquid crystal elastomers.

Two-stage thiol-acrylate Michael addition reactions have proven useful in programming main-chain liquid crystal elastomers (LCEs). However, the influence of excess acrylate concentration, which is critical to monodomain programming, has not previously been examined with respect to thermomechanical properties in these two-stage LCEs. Previous studies of thiol-acrylate LCEs have focused on polydomain LCEs and/or variation of thiol crosslinking monomers or linear thiol monomers. This study guides the design of monodomain LCE actuators using the two-stage methodology by varying the concentration of mesogenic acrylate monomers from 2 mol% to 45 mol% in stoichiometric excess of thiol. The findings demonstrate a technique to tailor the isotropic transition temperature by 44 °C using identical starting monomers. In contrast to expectations, low amounts of excess acrylate showed excellent fixity (90.4 ± 2.9%), while high amounts of excess acrylate did not hinder actuation strain (87.3 ± 2.3%). Tensile stress-strain properties were influenced by excess acrylate. Linear elastic behavior was observed parallel to the director with modulus increasing from 1.4 to 6.1 MPa. The soft elastic plateau was observed perpendicular to the director with initial modulus and threshold stresses increasing from 0.6 MPa to 2.6 MPa and 14 kPa to 208 kPa, respectively. Overall, this study examines the influence of excess acrylate on mechanical properties of LCE actuators.

Evaluation and Prediction of Human Lumbar Vertebrae Endplate Mechanical Properties Using Indentation and Computed Tomography.

Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (µm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver-Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.

Biological evaluation and finite-element modeling of porous poly(para-phenylene) for orthopaedic implants.

Poly(para-phenylene) (PPP) is a novel aromatic polymer with higher strength and stiffness than polyetheretherketone (PEEK), the gold standard material for polymeric load-bearing orthopaedic implants. The amorphous structure of PPP makes it relatively straightforward to manufacture different architectures, while maintaining mechanical properties. PPP is promising as a potential orthopaedic material; however, the biocompatibility and osseointegration have not been well investigated. The objective of this study was to evaluate biological and mechanical behavior of PPP, with or without porosity, in comparison to PEEK. We examined four specific constructs: 1) solid PPP, 2) solid PEEK, 3) porous PPP and 4) porous PEEK. Pre-osteoblasts (MC3T3) exhibited similar cell proliferation among the materials. Osteogenic potential was significantly increased in the porous PPP scaffold as assessed by ALP activity and calcium mineralization. In vivo osseointegration was assessed by implanting the cylindrical materials into a defect in the metaphysis region of rat tibiae. Significantly more mineral ingrowth was observed in both porous scaffolds compared to the solid scaffolds, and porous PPP had a further increase compared to porous PEEK. Additionally, porous PPP implants showed bone formation throughout the porous structure when observed via histology. A computational simulation of mechanical push-out strength showed approximately 50% higher interfacial strength in the porous PPP implants compared to the porous PEEK implants and similar stress dissipation. These data demonstrate the potential utility of PPP for orthopaedic applications and show improved osseointegration when compared to the currently available polymeric material. STATEMENT OF SIGNIFICANCE: PEEK has been widely used in orthopaedic surgery; however, the ability to utilize PEEK for advanced fabrication methods, such as 3D printing and tailored porosity, remain challenging. We present a promising new orthopaedic biomaterial, Poly(para-phenylene) (PPP), which is a novel class of aromatic polymers with higher strength and stiffness than polyetheretherketone (PEEK). PPP has exceptional mechanical strength and stiffness due to its repeating aromatic rings that provide strong anti-rotational biaryl bonds. Furthermore, PPP has an amorphous structure making it relatively easier to manufacture (via molding or solvent-casting techniques) into different geometries with and without porosity. This ability to manufacture different architectures and use different processes while maintaining mechanical properties makes PPP a very promising potential orthopaedic biomaterial which may allow for closer matching of mechanical properties between the host bone tissue while also allowing for enhanced osseointegration. In this manuscript, we look at the potential of porous and solid PPP in comparison to PEEK. We measured the mechanical properties of PPP and PEEK scaffolds, tested these scaffolds in vitro for osteocompatibility with MC3T3 cells, and then tested the osseointegration and subsequent functional integration in vivo in a metaphyseal drill hole model in rat tibia. We found that PPP permits cell adhesion, growth, and mineralization in vitro. In vivo it was found that porous PPP significantly enhanced mineralization into the construct and increased the mechanical strength required to push out the scaffold in comparison to PEEK. This is the first study to investigate the performance of PPP as an orthopaedic biomaterial in vivo. PPP is an attractive material for orthopaedic implants due to the ease of manufacturing and superior mechanical strength.

Copper-Coated Liquid-Crystalline Elastomer via Bioinspired Polydopamine Adhesion and Electroless Deposition.

This study explores the functionalization of main-chain nematic elastomers with a conductive metallic surface layer using a polydopamine binder. Using a two-stage thiol-acrylate reaction, a programmed monodomain is achieved for thermoreversible actuation. A copper layer (≈155 nm) is deposited onto polymer samples using electroless deposition while the samples are in their elongated nematic state. Samples undergo 42% contraction when heated above the isotropic transition temperature. During the thermal cycle, buckling of the copper layer is seen in the direction perpendicular to contraction; however, transverse cracking occurs due to the large Poisson effect experienced during actuation. As a result, the electrical conductivity of the layer reduced quickly as a function of thermal cycling. However, samples do not show signs of delamination after 25 thermal cycles. These results demonstrate the ability to explore multifunctional liquid-crystalline composites using relatively facile synthesis, adhesion, and deposition techniques.

Thermo-mechanical behavior and structure of melt blown shape-memory polyurethane nonwovens.

New processing methods for shape-memory polymers allow for tailoring material properties for numerous applications. Shape-memory nonwovens have been previously electrospun, but melt blow processing has yet to be evaluated. In order to determine the process parameters affecting shape-memory behavior, this study examined the effect of air pressure and collector speed on the mechanical behavior and shape-recovery of shape-memory polyurethane nonwovens. Mechanical behavior was measured by dynamic mechanical analysis and tensile testing, and shape-recovery was measured by unconstrained and constrained recovery. Microstructure changes throughout the shape-memory cycle were also investigated by micro-computed tomography. It was found that increasing collector speed increases elastic modulus, ultimate strength and recovery stress of the nonwoven, but collector speed does not affect the failure strain or unconstrained recovery. Increasing air pressure decreases the failure strain and increases rubbery modulus and unconstrained recovery, but air pressure does not influence recovery stress. It was also found that during the shape-memory cycle, the connectivity density of the fibers upon recovery does not fully return to the initial values, accounting for the incomplete shape-recovery seen in shape-memory nonwovens. With these parameter to property relationships identified, shape-memory nonwovens can be more easily manufactured and tailored for specific applications.

Temperature-Induced Switchable Adhesion using Nickel-Titanium-Polydimethylsiloxane Hybrid Surfaces.

A switchable dry adhesive based on a nickel-titanium (NiTi) shape-memory alloy with an adhesive silicone rubber surface has been developed. Although several studies investigate micropatterned, bioinspired adhesive surfaces, very few focus on reversible adhesion. The system here is based on the indentation-induced two-way shape-memory effect in NiTi alloys. NiTi is trained by mechanical deformation through indentation and grinding to elicit a temperature-induced switchable topography with protrusions at high temperature and a flat surface at low temperature. The trained surfaces are coated with either a smooth or a patterned adhesive polydimethylsiloxane (PDMS) layer, resulting in a temperature-induced switchable surface, used for dry adhesion. Adhesion tests show that the temperature-induced topographical change of the NiTi influences the adhesive performance of the hybrid system. For samples with a smooth PDMS layer the transition from flat to structured state reduces adhesion by 56%, and for samples with a micropatterned PDMS layer adhesion is switchable by nearly 100%. Both hybrid systems reveal strong reversibility related to the NiTi martensitic phase transformation, allowing repeated switching between an adhesive and a nonadhesive state. These effects have been discussed in terms of reversible changes in contact area and varying tilt angles of the pillars with respect to the substrate surface.

Monotonic and cyclic loading behavior of porous scaffolds made from poly(para-phenylene) for orthopedic applications.

Porous poly(para-phenylene) (PPP) scaffolds have tremendous potential as an orthopedic biomaterial; however, the underlying mechanisms controlling the monotonic and cyclic behavior are poorly understood. The purpose of this study was to develop a method to integrate micro-computed tomography (µCT), finite-element analysis (FEA), and experimental results to uncover the relationships between the porous structure and mechanical behavior. The µCT images were taken from porous PPP scaffolds with a porosity of 75vol% and pore size distribution between 420 and 500µm. Representative sections of the image were segmented and converted into finite-element meshes. It was shown through FEA that localized stresses within the microstructure were approximately 100 times higher than the applied global stress during the linear loading regime. Experimental analysis revealed the S-N fatigue curves for fully dense and porous PPP samples were parallel on log-log plots, with the endurance limit for porous samples in tension being approximately 100 times lower than their solid PPP counterparts (0.3-35MPa) due to the extreme stress concentrations caused by the porous microarchitecture. The endurance limit for porous samples in compression was much higher than in tension (1.60MPa). Through optical, laser-scanning, and scanning-electron microscopy it was found that porous tensile samples failed under Mode I fracture in both monotonic and cyclic loading. By comparison, porous compressive samples failed via strut buckling/pore collapse monotonically and by shearing fracture during cyclic loading. Monotonic loading showed that deformation behavior was strongly correlated with pore volume fraction, matching foam theory well; however, fatigue behavior was much more sensitive to local stresses believed to cause crack nucleation.

High-strength poly(para-phenylene) as an orthopedic biomaterial.

Poly(para-phenylene) (PPP) exhibits exceptional mechanical strength, stiffness, toughness, and chemical inertness, although it is not currently used in any biomedical applications. The purpose of this study is to serve as a preliminary investigation into the potential of PPP as a biomaterial in orthopedic load-bearing applications. Nuclear magnetic resonance (NMR) analysis confirmed a polymer structure composed of an aromatic backbone and side groups. Tensile PPP specimens along with samples from several other polymers often used for orthopedic applications were elongated to failure after being soaked in phosphate buffered saline (PBS) for 1 h, 1 day, 1 week, 2 weeks, 1 month, and more than 1 year. Results showed that PBS absorption of the PPP plateaued at 1 week at values of ∼0.7 wt % and remained within one standard deviation when soaked for over 1 year. PBS absorption did not affect elastic modulus (5.0 GPa), yield strength (141 MPa), fracture strength (120 MPa) and strain-to-failure (17%) more than one standard deviation. Zero-to-tension fatigue testing established an endurance limit of approximately 35 MPa, which was relatively insensitive to frequency (1-10 Hz). Eagle's minimum essential medium (MEM) elution assay with fibroblasts confirmed that the PPP was noncytotoxic. Relative to other polymers used for load-bearing biomedical applications, PPP displays promising mechanical properties that remain stable in aqueous solution. Lastly, prototype PPP and polyetheretherketone (PEEK) bone plates were manufactured and tested, with the PPP plate showing a 38% higher maximum tensile load before failure.

Porous poly(para-phenylene) scaffolds for load-bearing orthopedic applications.

The focus of this study was to fabricate and investigate the mechanical behavior of porous poly(para-phenylene) (PPP) for potential use as a load-bearing orthopedic biomaterial. PPPs are known to have exceptional mechanical properties due to their aromatic backbone; however, the manufacturing and properties of PPP porous structures have not been previously investigated. Tailored porous structures with either small (150-250µm) or large (420-500µm) pore sizes were manufactured using a powder-sintering/salt-leaching technique. Porosities were systematically varied using 50 to 90vol%. Micro-computed tomography (µCT) and scanning electron microscopy (SEM) were used to verify an open-cell structure and investigate pore morphology of the scaffolds. Uniaxial mechanical behavior of solid and porous PPP samples was characterized through tensile and compressive testing. Both modulus and strength decreased with increasing porosity and matched well with foam theory. Porous scaffolds showed a significant decrease in strain-to-failure (<4%) under tensile loading and experienced linear elasticity, plastic deformation, and densification under compressive loading. Over the size ranges tested, pore size did not significantly influence the mechanical behavior of the scaffolds on a consistent basis. These results are discussed in regards to use of porous PPP for orthopedic applications and a prototype porous interbody fusion cage is presented.

Detachment behavior of mushroom-shaped fibrillar adhesive surfaces in peel testing.

Synthetic dry adhesive surfaces with mushroom-shaped pillars have been the subject of recent research investigation. This study is the first to systematically investigate the effect of peel angle, pillar diameter, and pillar aspect ratio on the force required for peeling. Explicit emphasis was placed on relatively large pillar structures to allow for in situ optical visualization in order to gain insights into fundamental mechanisms which dictate peeling. Traditional molding techniques were used to fabricate optical-scale mushroom terminated structures with pillar diameters of 1 mm and 400 µm and aspect ratios of 1, 3, and 5. Results were quantitatively compared to peel testing theory for conventional adhesives. It was convincingly demonstrated that the critical decohesion energy of a patterned surface changes as a function of angle and cannot be treated as a constant. Variability in the critical decohesion energy was linked to mechanistic differences in detachment through in situ observations and finite element analysis (FEA). Experimental results showed that smaller pillars do not necessarily lead to higher adhesion during peeling, and contact mechanics combined with optical observations were used to explain this phenomenon. Finally, unlike results from normal adhesion studies, aspect ratio was shown to play little role in peeling adhesive behavior due to the mechanics of peel testing. The results and conclusions from this study uncover the detachment mechanisms of mushroom-shape tipped dry adhesives under peel loading and serve as an outline for the design of these surfaces in peeling applications.

Thermally switchable adhesion of photopolymerizable acrylate polymer networks - biomed 2013.

Switchable adhesion behavior of flat and structured photopolymerizable acrylate networks was investigated as a function of temperature. The molecular weight and the weight fraction of poly(ethylene glycol) dimethacrylate crosslinker was altered to maintain a constant glass transition temperature of approximately 57°C, but systematically vary the viscoelastic properties and the rubbery moduli (1.8-11.2 MPa). Dynamic mechanical analysis was performed to characterize the low-strain thermo-mechanical behavior of the materials. The flat samples tested with the spherical probe exhibited low pull-off forces at temperatures well above and well below the glass transition temperature of the material. A maximum pull-off force was observed in the vicinity of the glass transition temperature owing to the viscoelastic energy dissipative processes. The peak in pull-off force was observed to decrease with an increase in crosslinking density and modulus. The structured samples tested with spherical probe showed a decrease in adhesion with an increase in temperature up to the onset of glass transition, beyond which the adhesion was observed to increase due to the better contact formation allowed by the decrease in the material modulus.

Tensile behavior of porous scaffolds made from poly(para phenylene) - biomed 2013.

The goal of this study was to fabricate and mechanically characterize a high-strength porous polymer scaffold for potential use as an orthopedic device. Poly(para-phenylene) (PPP) is an excellent candidate due to its exceptional strength and stiffness and relative inertness, but has never been explicitly investigated for use as a biomedical device. PPP has strength values 3 to 10 times higher and an elastic modulus nearly an order of magnitude higher than traditional polymers such as poly(methyl methacrylate) (PMMA), polycaprolactone (PCL), ultra-high molecular weight polyethylene (UHMWPE), and polyurethane (PU) and is significantly stronger and stiffer than polyetheretherketone (PEEK). By utilizing PPP we can overcome the mechanical limitations of traditional porous polymeric scaffolds since the outstanding stiffness of PPP allows for a highly porous structure appropriate for osteointegration that can match the stiffness of bone (100-250 MPa), while maintaining suitable mechanical properties for soft-tissue fixation. Porous samples were manufactured by powder sintering followed by particle leaching. The pore volume fraction was systematically varied from 50–80 vol% for a pore sizes from150-500 µm, as indicated by previous studies for optimal osteointegration. The tensile modulus of the porous samples was compared to the rule of mixtures, and closely matches foam theory up to 70 vol%. The experimental modulus for 70 vol% porous samples matches the stiffness of bone and contains pore sizes optimal for osteointegration.

Tensile deformation of NiTi wires.

We examine the structure and properties of cold drawn Ti-50.1 at % Ni and Ti-50.9 at % Ni shape memory alloy wires. Wires with both compositions possess a strong <111> fiber texture in the wire drawing direction, a grain size on the order of micrometers, and a high dislocation density. The more Ni rich wires contain fine second phase precipitates, while the wires with lower Ni content are relatively free of precipitates. The wire stress-strain response depends strongly on composition through operant deformation mechanisms, and cannot be explained based solely on measured differences in the transformation temperatures. We provide fundamental connections between the material structure, deformation mechanisms, and resulting stress-strain responses. The results help clarify some inconsistencies and common misconceptions in the literature. Ramifications on materials selection and design for emerging biomedical applications of NiTi shape memory alloys are discussed.