Repurposing of waste PET by microbial biotransformation to functionalized materials for additive manufacturing.

Plastic waste is an outstanding environmental thread. Poly(ethylene terephthalate) (PET) is one of the most abundantly produced single-use plastics worldwide, but its recycling rates are low. In parallel, additive manufacturing is a rapidly evolving technology with wide-ranging applications. Thus, there is a need for a broad spectrum of polymers to meet the demands of this growing industry and address post-use waste materials. This perspective article highlights the potential of designing microbial cell factories to upcycle PET into functionalized chemical building blocks for additive manufacturing. We present the leveraging of PET hydrolyzing enzymes and rewiring the bacterial C2 and aromatic catabolic pathways to obtain high-value chemicals and polymers. Since PET mechanical recycling back to original materials is cost-prohibitive, the biochemical technology is a viable alternative to upcycle PET into novel 3D printing materials, such as replacements for acrylonitrile butadiene styrene. The presented hybrid chemo-bio approaches potentially enable the manufacturing of environmentally friendly degradable or higher-value high-performance polymers and composites and their reuse for a circular economy. ONE-SENTENCE SUMMARY: Biotransformation of waste PET to high-value platform chemicals for additive manufacturing.

Merging versatile polymer chemistry with multifunctional nanoparticles: an overview of crosslinkable aromatic polyester matrix nanocomposites.

The current trend in the global advanced material market is expeditiously shifting towards more lightweight, multifunctional configurations, considering very recent developments in electrical aircraft, biomedical devices, and autonomous automobiles. Hence, the development of novel polymer nanocomposite materials is critical to advancing the current state-of-the-art of structural material technologies to address the pressing performance demands. Aiming at expanding the existing material design space, we have investigated crosslinkable aromatic polyester matrix nanocomposites. Aromatic polyesters, in the thermosetting form, are a prospective high-performance/high-temperature polymer technology, which is on a par with conventional epoxy-derivative resins and high-performance engineering thermoplastics in the range of their potential applications. The aromatic matrix-based thermosetting nanocomposites manifest greatly enhanced physical properties enabled by a chemistry-favored robust interfacial covalent coupling mechanism developed during the in situ polymerization reaction with various nanofiller particle configurations. Here, we provide a summary review of our recent efforts in developing this novel polymer nanocomposite material system. We highlight the chemical strategy, fabrication approach, and processing techniques developed to obtain various nanocomposite representations for structural, electrical, optical, biomedical, and tribological applications. The unique characteristic features emerging in the nanocomposite morphologies, along with their physicochemical effects on the multifunctional macroscale properties, are demonstrated. This unique matrix configuration introduces superior performance elements to polymer nanocomposite applications towards designing advanced composite materials.

Deproteinization of Cortical Bone: Effects of Different Treatments.

Bone is a biological composite material having collagen and mineral as its main constituents. In order to better understand the arrangement of the mineral phase in bone, porcine cortical bone was deproteinized using different chemical treatments. This study aims to determine the best method to remove the protein constituent while preserving the mineral component. Chemicals used were H2O2, NaOCl, NaOH, and KOH, and the efficacy of deproteinization treatments was determined by thermogravimetric analysis and Raman spectroscopy. The structure of the residual mineral parts was examined using scanning electron microscopy. X-ray diffraction was used to confirm that the mineral component was not altered by the chemical treatments. NaOCl was found to be the most effective method for deproteinization and the mineral phase was self-standing, supporting the hypothesis that bone is an interpenetrating composite. Thermogravimetric analyses and Raman spectroscopy results showed the preservation of mineral crystallinity and presence of residual organic material after all chemical treatments. A defatting step, which has not previously been used in conjunction with deproteinization to isolate the mineral phase, was also used. Finally, Raman spectroscopy demonstrated that the inclusion of a defatting procedure resulted in the removal of some but not all residual protein in the bone.

Modeling of Stiffness and Strength of Bone at Nanoscale.

Two distinct geometrical models of bone at the nanoscale (collagen fibril and mineral platelets) are analyzed computationally. In the first model (model I), minerals are periodically distributed in a staggered manner in a collagen matrix while in the second model (model II), minerals form continuous layers outside the collagen fibril. Elastic modulus and strength of bone at the nanoscale, represented by these two models under longitudinal tensile loading, are studied using a finite element (FE) software abaqus. The analysis employs a traction-separation law (cohesive surface modeling) at various interfaces in the models to account for interfacial delaminations. Plane stress, plane strain, and axisymmetric versions of the two models are considered. Model II is found to have a higher stiffness than model I for all cases. For strength, the two models alternate the superiority of performance depending on the inputs and assumptions used. For model II, the axisymmetric case gives higher results than the plane stress and plane strain cases while an opposite trend is observed for model I. For axisymmetric case, model II shows greater strength and stiffness compared to model I. The collagen-mineral arrangement of bone at nanoscale forms a basic building block of bone. Thus, knowledge of its mechanical properties is of high scientific and clinical interests.

Employing the biology of successful fracture repair to heal critical size bone defects.

Bone has the natural ability to remodel and repair. Fractures and small noncritical size bone defects undergo regenerative healing via coordinated concurrent development of skeletal and vascular elements in a soft cartilage callus environment. Within this environment bone regeneration recapitulates many of the same cellular and molecular mechanisms that form embryonic bone. Angiogenesis is intimately involved with embryonic bone formation and with both endochondral and intramembranous bone formation in differentiated bone. During bone regeneration osteogenic cells are first associated with vascular tissue in the adjacent periosteal space or the adjacent injured marrow cavity that houses endosteal blood vessels. Critical size bone defects cannot heal without the assistance of therapeutic aids or materials designed to encourage bone regeneration. We discuss the prospects for using synthetic hydrogels in a bioengineering approach to repair critical size bone defects. Hydrogel scaffolds can be designed and fabricated to potentially trigger the same bone morphogenetic cascade that heals bone fractures and noncritical size defects naturally. Lastly, we introduce adult Xenopus laevis hind limb as a novel small animal model system for bone regeneration research. Xenopus hind limbs have been used successfully to screen promising scaffolds designed to heal critical size bone defects.

Viscoelastic properties of the equine hoof wall.

The equine hoof wall has outstanding impact resistance, which enables high-velocity gallop over hard terrain with minimum damage. To better understand its viscoelastic behavior, complex moduli were determined using two complementary techniques: conventional (∼5 mm length scale) and nano (∼1 µm length scale) dynamic mechanical analysis (DMA). The evolution of their magnitudes was measured for two hydration conditions: fully hydrated and ambient. The storage modulus of the ambient hoof wall was approximately 400 MPa in macro-scale experiments, decreasing to ∼250 MPa with hydration. In contrast, the loss tangent decreased for both hydrated (∼0.1-0.07) and ambient (∼0.04-0.01) conditions, over the frequency range of 1-10 Hz. Nano-DMA indentation tests conducted up to 200 Hz showed little frequency dependence beyond 10 Hz. The loss tangent of tubular regions showed more hydration sensitivity than in intertubular regions, but no significant difference in storage modulus was observed. Loss tangent and effective stiffness were higher in indentations for both hydration levels. This behavior is attributed to the hoof wall's hierarchical structure, which has porosity, functionally graded aspects, and material interfaces that are not captured at the scale of indentation. The hoof wall's viscoelasticity characterized in this work has implications for the design of bioinspired impact-resistant materials and structures. STATEMENT OF SIGNIFICANCE: The outer wall of horse hooves evolved to withstand heavy impacts during gallop. While previous studies have measured the properties of the hoof wall in slowly changing conditions, we wanted to quantify its behavior using experiments that replicate the quickly changing forces of impact. Since the hoof wall's structure is complex and contributes to its overall performance, smaller scale experiments were also performed. The behavior of the hoof wall was within the range of other biological materials and polymers. When hydrated, it becomes softer and can dissipate more energy. This work improves our understanding of the hoof's function and allows for more accurate simulations that can account for different impact speeds.

Exploring the Effect of Specimen Size on Elastic Properties of Fused-Filament-Fabrication-Printed Polycarbonate and Thermoplastic Polyurethane.

Additive manufacturing (AM) is often used to create designs inspired by topology optimization and biological structures, yielding unique cross-sectional geometries spanning across scales. However, manufacturing defects intrinsic to AM can affect material properties, limiting the applicability of a uniform material model across diverse cross-sections. To examine this phenomenon, this paper explores the influence of specimen size and layer height on the compressive modulus of polycarbonate (PC) and thermoplastic polyurethane (TPU) specimens fabricated using fused filament fabrication (FFF). Micro-computed tomography imaging and compression testing were conducted on the printed samples. The results indicate that while variations in the modulus were statistically significant due to both layer height and size of the specimen in TPU, variations in PC were only statistically significant due to layer height. The highest elastic modulus was observed at a 0.2 mm layer height for both materials across different sizes. These findings offer valuable insights into design components for FFF, emphasizing the importance of considering mechanical property variations due to feature size, especially in TPU. Furthermore, locations with a higher probability of failure are recommended to be printed closer to the print bed, especially for TPU, because of the lower void volume fraction observed near the heated print bed.

Correlation between reference point indentation and mechanical properties of 3D-printed polymers.

Reference point indentation (RPI) is a novel experimental technique designed to evaluate bone quality. This study utilizes two RPI instruments, BioDent and Osteoprobe, to investigate the mechanical responses of several 3D-printed polymers. We correlated the mechanical properties from a tensile test with the RPI parameters obtained from the BioDent and OsteoProbe. In addition, we tested the same polymers five years later (Age 5). The results show that for Age 0 polymers, the elastic modulus is highly correlated with average unloading slope (r = 0.87), first unloading slope (r = 0.85), bone material strength index (BMSi) (r = 0.85), average loading slope (r = 0.82), first indentation distance (r = 0.79), and total indentation distance (r = 0.76). The ultimate stress correlates significantly with first unloading slope (r = 0.85), average unloading slope (r = 0.83), BMSi (r = 0.81), first indentation distance (r = 0.73), average loading slope (r = 0.71), and total indentation distance (r = 0.70). The elongation has no significant correlation with the RPI parameters except with the average creep indentation distance (r = 0.60). For Age 5 polymers, correlations between mechanical properties and RPI parameters are low. This study illustrates the potential of RPI to assess the mechanical properties of polymers nondestructively with simple sample requirements. Furthermore, for the first time, 3D-printed polymers and aged polymers are investigated with RPI.

Bone resorption markers and dual-energy x-ray absorptiometry in dogs with avascular necrosis, degenerative joint disease, and trauma of the coxofemoral joint.

OBJECTIVES: To compare the ability of N-terminal telopeptide (NTx) assays and dual-energy x-ray absorptiometry (DEXA) to detect bone resorption in dogs with nonneoplastic bone lysis and evaluate the correlation between these diagnostic tools. STUDY DESIGN: Prospective, cross-sectional clinical study. ANIMALS: Dogs (n = 35; 39 femoral heads) that had femoral head and neck ostectomy and 6 cadaver specimens from healthy immature small dogs. METHODS: Small dogs with avascular necrosis (n = 12), a reference group of small dogs (7), large dogs with degenerative joint disease (DJD; 10), and large dogs with trauma (10) were studied in addition to 6 femoral heads harvested from 6 small immature and healthy dogs euthanatized for reasons unrelated to this study. Densitometric measurements of femoral heads, urine NTx excretion, and serum NTx concentration were compared between groups. RESULTS: Avascular necrosis resulted in a decrease in bone mineral density (BMD) (0.18 ± 0.01 g/cm(2;) P < .01) of the femoral head and elevation of serum NTx (159.3 ± 59.4 nM; P = .03) compared to small dog controls (0.28 ± 0.02 g/cm(2) ; 18.7 ± 1.83 nM, respectively), but did not seem to affect urine NTx. DJD in large dogs did not seem to affect any of the densitometric parameters evaluated. BMD (P = .03) and serum NTx (P = .04) were lower in small compared to large dogs. Serum NTx and densitometric measurements correlate inversely with each other (P = .001) but neither test correlated with urine NTx (P = .8-.9). CONCLUSION: Serum NTx levels vary with dog size but seem to correlate better with BMD better than urine NTx excretion in dogs with nonneoplastic bone resorption.

Biomimetic design of implants for long bone critical-sized defects.

This computational study addresses new biomimetic load-bearing implants designed to treat long bone critical-sized defects in a proximal diaphysis region. The design encompasses two strategies: a Haversian bone-mimicking approach for cortical bone and lattices based on triply periodic minimal surfaces (TPMS) for trabecular bone. Compression tests are modeled computationally via a non-linear finite element analysis with Ti6Al4V alloy as a base material. Nine topologies resembling cortical bone are generated as hollow cylinders with different channel arrangements simulating Haversian (longitudinal) and Volkmann (transverse) canals to achieve properties like those of a human cortical bone (Strategy I). Then, the selected optimal structure from Strategy I is merged with the trabecular bone part represented by four types of TPMS-based lattices (Diamond, Primitive, Split-P, and Gyroid) with the same relative density to imitate the whole bone structure. The Strategy I resulted in finding a hollow cylinder including Haversian and Volkmann canals, optimized in canals number, shape, and orientation to achieve mechanical behavior close to human cortical bone. The surface area and volume created by such canals have the maximum values among all studied combinations of transverse and longitudinal channels. Strategy II reveals the effect of interior design on the load-bearing capacity of the whole component. Between four types of selected TPMS, Diamond-based lattice and Split-P have more uniform stress distribution, resulting in a superior load-bearing efficiency than Gyroid and Primitive-based design showing less uniformity. This work offers a new design of the bone-mimicking implant, with cortical and trabecular bone components, to repair long bone critical-sized defects.

Hierarchical modeling of elastic moduli of equine hoof wall.

This study predicts analytically effective elastic moduli of substructures within an equine hoof wall. The hoof wall is represented as a composite material with a hierarchical structure comprised of a sequence of length scales. A bottom-up approach is employed. Thus, the outputs from a lower spatial scale serve as the inputs for the following scale. The models include the Halpin-Tsai model, composite cylinders model, a sutured interface model, and classical laminate theory. The length scales span macroscale, mesoscale, sub-mesoscale, microscale, sub-microscale, and nanoscale. The macroscale represents the hoof wall, consisting of tubules within a matrix at the mesoscale. At the sub-mesoscale, a single hollow tubule is reinforced by a tubule wall made of lamellae; the surrounding intertubular material also has a lamellar structure. The lamellae contain sutured and layered cells at the microscale. A single cell is made of crystalline macrofibrils arranged in an amorphous matrix at the sub-microscale. A macrofibril contains aligned crystalline rod-like intermediate filaments at the nanoscale. Experimentally obtained parameters are used in the modeling as inputs for geometry and nanoscale properties. The predicted properties of the hoof wall material agree with experimental measurements at the mesoscale and macroscale. We observe that the hierarchical structure of the hoof wall leads to a decrease in the elastic modulus with increasing scale, from the nanoscale to the macroscale. Such behavior is an intrinsic characteristic of hierarchical biological materials. This study can serve as a framework for designing impact-resistant hoof-inspired materials and structures.

Equine hoof wall: Structure, properties, and bioinspired designs.

The horse hoof wall exhibits exceptional impact resistance and fracture control due to its unique hierarchical structure which contains tubular, lamellar, and gradient configurations. In this study, structural characterization of the hoof wall was performed revealing features previously unknown. Prominent among them are tubule bridges, which are imaged and quantified. The hydration-dependent viscoelasticity of the hoof wall is described by a simplified Maxwell-Weichert model with two characteristic relaxation times corresponding to nanoscale and mesoscale features. Creep and relaxation tests reveal that the specific hydration gradient in the hoof keratin likely leads to reduced internal stresses that arise from spatial stiffness variations. To better understand realistic impact modes for the hoof wall in-vivo, drop tower tests were executed on hoof wall samples. Fractography revealed that the hoof wall's reinforced tubular structure dominates at lower impact energies, while the intertubular lamellae are dominant at higher impact energies. Broken fibers were observed on the surface of the tubules after failure, suggesting that the physically intertwined nature of the tubule reinforcement and intertubular matrix improves the toughness of this natural fiber reinforced composite. The augmented understanding of the structure-mechanical property relationship in dynamic loading led to the design of additively manufactured bioinspired structures, which were evaluated in quasistatic and dynamic loadings. The inclusion of gradient structures and lamellae significantly reduced the damage sustained in drop tower tests, while tubules increased the energy absorption of samples tested in compact tension. The samples most similar to the hoof wall displayed remarkably consistent fracture control properties. STATEMENT OF SIGNIFICANCE: The horse hoof wall, capable of withstanding large, repeated, dynamic loads, has been touted as a candidate for impact-resistant bioinspiration. However, our understanding of this biological material and its translation into engineered designs is incomplete. In this work, new features of the horse hoof wall are quantified and the hierarchical failure mechanisms of this remarkable material under near-natural loading conditions are uncovered. A model of the hoof wall's viscoelastic response, based on studies of other keratinous materials, was developed. The role of hydration, strain rate, and impact energy on the material's response were elucidated. Finally, multi-material 3D printed designs based on the hoof's meso/microstructure were fabricated and exhibited advantageous energy absorption and fracture control relative to control samples.

Modeling of bending and torsional stiffnesses of bone at sub-microscale: Effect of curved mineral lamellae.

Recent transmission electron microscopy images of transverse sections of human cortical bone showed that mineral lamellae (polycrystalline sheets of apatite crystals) form arcuate multi-radius patterns around collagen fibrils. The 3-6 nm thick mineral lamellae are arranged in stacks of 3-20 layers and curve around individual fibrils, few fibrils, and higher numbers of collagen fibrils. We evaluate the effect of these stacked mineral lamellae with various radius of curvature patterns on the elastic bending and torsional responses of bone at the sub-microscale using a finite element method. We find that the curved multi-radius stack patterns increased the bending and torsional stiffnesses by 7% and 23%, respectively, compared to when the stacks of mineral lamellae only encircle individual fibrils for the idealized geometric models considered. This study provides new insights into the structure-property relations for the bone ultrastructure.

Interfacial bonding between mineral platelets in bone and its effect on mechanical properties of bone.

Bone is a composite material consisting principally of apatite mineral, collagen fibrils, non-collagenous proteins, and other organic species. Recent electron microscopy studies have shown that the mineral in bone occurs as stacks of thin polycrystalline sheets ("mineral lamellae," MLs) which surround and lie between the collagen fibrils. We focus on the effect of the interface between these mineral lamellae on the mechanical properties of bone. Previous studies on bone treated with sodium hypochlorite (NaClO) to remove all organic material showed a greatly weakened mineral framework. Here, we treated femoral cortical bone with ethylenediamine (EDA), which only removes collagen, to study the effect of its removal on bone properties. We tested the degree of completion of the treatment by Raman spectroscopy and thermogravimetric analysis. When only collagen is removed, a continuous mineral structure remains and is less weakened than by NaClO treatment. Transmission electron microscopy study of finely ground particles of the EDA treated bone shows that stacks of MLs remain joined, whereas in NaClO treated bone, only isolated crystals are present. Thus, we infer that the MLs in bone are held together in stacks by an organic glue, which is destroyed by NaClO, but which survives the EDA treatment. We show that this glue may contribute to the stiffness, strength, and energy absorption of bone. Further studies are needed to discover the chemical nature of this glue. This study provides a starting point for such investigations.

High-Performance Computing Comparison of Implicit and Explicit Nonlinear Finite Element Simulations of Trabecular Bone.

BACKGROUND AND OBJECTIVE: Finite element models built from micro-computed tomography scans have become a powerful tool to investigate the mechanical properties of trabecular bone. There are two types of solving algorithms in the finite element method: implicit and explicit. Both of these methods have been utilized to study the trabecular bone. However, an investigation comparing the results obtained using the implicit and explicit solvers is lacking. Thus, in this paper, we contrast implicit and explicit procedures by analyzing trabecular bone samples as a case study. METHODS: Micro-computed tomography-based finite element analysis of trabecular bone under a direct quasi-static compression was done using implicit and explicit methods. The differences in the predictions of mechanical properties and computational time of the two methods were studied using high-performance computing. RESULTS: Our findings indicate that the results using implicit and explicit solvers are well comparable, given that similar problem set up is carefully utilized. Also, the parallel scalability of the two methods was similar, while the explicit solver performed about five times faster than the implicit method. Along with faster performance, the explicit method utilized significantly less memory for the analysis, which shows another benefit of using an explicit solver for this case study. CONCLUSIONS: The comparison of the implicit and explicit methods for the simulation of trabecular bone samples should be highly valuable to the bone modeling community and researchers studying complex cellular and architectured materials.

Comparison of different protocols for demineralization of cortical bone.

Bone is a biological composite material consisting of two main components: collagen and mineral. Collagen is the most abundant protein in vertebrates, which makes it of high clinical and scientific interest. In this paper, we compare the composition and structure of cortical bone demineralized using several protocols: ethylene-diamine-tetraacetic acid (EDTA), formic acid (CH2O2), hydrochloric acid (HCl), and HCl/EDTA mixture. The efficiencies of these four agents were investigated by assessing the remaining mineral quantities and collagen integrity with various experimental techniques. Raman spectroscopy results show that the bone demineralized by the CH2O2 agent has highest collagen quality parameter. The HCl/EDTA mixture removes the most mineral, but it affects the collagen secondary structure as amide II bands are shifted as observed by Fourier transform infrared spectroscopy. Thermogravimetric analysis reveals that HCl and EDTA are most effective in removing the mineral with bulk measurements. In summary, we conclude that HCl best demineralizes bone, leaving the well-preserved collagen structure in the shortest time. These findings guide on the best demineralization protocol to obtain high-quality collagen from bone for clinical and scientific applications.

Engineering with keratin: A functional material and a source of bioinspiration.

Keratin is a highly multifunctional biopolymer serving various roles in nature due to its diverse material properties, wide spectrum of structural designs, and impressive performance. Keratin-based materials are mechanically robust, thermally insulating, lightweight, capable of undergoing reversible adhesion through van der Waals forces, and exhibit structural coloration and hydrophobic surfaces. Thus, they have become templates for bioinspired designs and have even been applied as a functional material for biomedical applications and environmentally sustainable fiber-reinforced composites. This review aims to highlight keratin's remarkable capabilities as a biological component, a source of design inspiration, and an engineering material. We conclude with future directions for the exploration of keratinous materials.

Multimodal characterization of the bone-implant interface using Raman spectroscopy and nanoindentation.

Titanium implants are widely used in dental and orthopedic surgeries. Osseointegration phenomena lead to direct contact between bone tissue and the implant surface. The quality of the bone-implant interface (BII), resulting from the properties of newly formed bone, determines the implant stability. This study investigates the BII properties using a dedicated in vivo implant model consisting of a coin-shaped Ti-6Al-4V implant inserted in a rabbit femur for 10 weeks. A gap created below the implant was filled with newly formed bone tissue after healing. The properties of mature and newly formed bone tissues were compared using: i) Raman spectroscopy to assess the nanoscale compositional bone properties and ii) nanoindentation to quantify microscale elastic properties in site-matched regions. The mineral-to-matrix ratio, crystallinity (mineral size and lattice order), and the collagen cross-link ratio were significantly lower in newly formed bone tissue (e.g., a mineral-to-matrix ratio of 9.3 ± 0.5 for proline 853 cm-1) compared to mature bone (15.6 ± 1). Nanoindentation measurements gave Young's modulus of 12.8 ± 1.8 GPa for newly formed bone and 15.7 ± 2.3 GPa for mature bone. This multimodal and multiscale approach leads to a better understanding of osseointegration phenomena.

Scale and boundary conditions effects on the apparent elastic moduli of trabecular bone modeled as a periodic cellular solid.

We study apparent elastic moduli of trabecular bone, which is represented, for simplicity, by a two- or three-dimensional periodic cellular network. The term "apparent" refers to the case when the region used in calculations (or specimen size) is smaller than a representative volume element and the moduli depend on the size of that region and boundary conditions. Both the bone tissue forming the network and the pores (represented by a very soft material) are assumed, for simplicity, as homogeneous, linear elastic, and isotropic. In order to investigate the effects of scale and boundary conditions on the moduli of these networks we vary the specimen size and apply four different boundary conditions: displacement, traction, mixed, and periodic. The analysis using periodic boundary conditions gives the effective moduli, while the displacement, traction, and mixed boundary conditions give apparent moduli. The apparent moduli calculated using displacement and traction boundary conditions bound the effective moduli from above and below, respectively. The larger is the size of the region used in our calculations, the closer are the bounds. Our choice of mixed boundary conditions gives results that are very close to those obtained using periodic boundary conditions. We conduct this analysis computationally using a finite element method. We also investigate the effect of mismatch in elastic moduli of bone tissue and soft fill, trabecular bone structure geometry, and bone tissue volume fraction on the apparent elastic moduli of idealized periodic models of trabecular bone. This study gives guidance on how the size of the specimen and boundary conditions (used in experiments or simulations) influence elastic moduli of cellular materials. This approach is applicable to heterogeneous materials in general.

Modeling of Osteoprobe indentation on bone.

Osteoprobe (ActiveLife, Santa Barbara, CA) is a novel handheld microindentation instrument designed to test bone in vivo by measuring a Bone Material Strength index (BMSi). In this paper, the Osteoprobe indentation on a cortical bone is modeled computationally to gain insights into the physical interpretation of the BMSi output. The analysis is conducted using an axisymmetric finite element model with an isotropic viscoelastic-plastic constitutive law with continuum damage. The computational model is validated by comparing it with experimental data from the literature. Experimental factors (indenter tip radius and friction coefficient between the indenter and the bone) and four mechanical properties of bone (Young's modulus, compressive yield stress, and damage and viscosity constants) are varied to study their influence on the BMSi. We find that varying the friction coefficient can proportionally change the BMSi up to 3%. The indenter tip radius is proportional to the BMSi, with a more pronounced proportional relation when it is greater than 30 µm. Young's modulus has a proportional relation with the BMSi, where decreasing it by 73% reduces the BMSi by 41%. The damage constant has an inversely proportional relation to the BMSi, where increasing it from 0.5 to 0.96 reduces the BMSi by 29%. The compressive yield stress and the viscosity constant have a close proportional relation to the BMSi, where increasing the compressive yield stress from 50 MPa to 200 MPa increases the Osteoprobe BMSi by 21%. In summary, the friction coefficient and the indenter tip radius (when smaller than 30 µm) have a small effect on BMSi. Young's modulus and damage have stronger relations with the BMSi than compressive yield stress and viscosity constant. This fundamental study provides new insights into the BMSi measurement and serves as a basis for further computational and experimental investigations on the Osteoprobe technique. Such research is needed to facilitate the embrace of this technique by the clinical community.