Porosity and surface curvature effects on the permeability and wall shear stress of trabecular bone: Guidelines for biomimetic scaffolds for bone repair.

Scaffolds are an essential component of bone tissue engineering to provide support and create a physiological environment for cells. Biomimetic scaffolds are a promising approach to fulfill the requirements. Bone allografts are widely used scaffolds due to their mechanical and structural characteristics. The scaffold geometry is well known to be an important determinant of induced mechanical stimulation felt by the cells. However, the impact of allograft geometry on permeability and wall shear stress distribution is not well understood. This information is essential for designing biomimetic scaffolds that provide a suitable environment for cells to proliferate and differentiate. The present study investigates the effect of geometry on the permeability and wall shear stress of bone allografts at both macroscopic and microscopic scales. Our results concluded that the wall shear stress was strongly correlated with the porosity of the allograft. The level of wall shear stress at a local scale was also determined by the surface curvature characteristics. The results of this study can serve as a guideline for future biomimetic scaffold designs that provide a mechanical environment favorable for osteogenesis and bone repair.

In Vivo Assessment of Skin Surface Pattern: Exploring Its Potential as an Indicator of Bone Biomechanical Properties.

The mechanical properties of bone tissue are the result of a complex process involving collagen-crystal interactions. The mineral density of the bone tissue is correlated with bone strength, whereas the characteristics of collagen are often associated with the ductility and toughness of the bone. From a clinical perspective, bone mineral density alone does not satisfactorily explain skeletal fragility. However, reliable in vivo markers of collagen quality that can be easily used in clinical practice are not available. Hence, the objective of the present study is to examine the relationship between skin surface morphology and changes in the mechanical properties of the bone. An experimental study was conducted on healthy children (n = 11), children with osteogenesis imperfecta (n = 13), and women over 60 years of age (n = 22). For each patient, the skin characteristic length (SCL) of the forearm skin surface was measured. The SCL quantifies the geometric patterns formed by wrinkles on the skin's surface, both in terms of size and elongation. The greater the SCL, the more deficient was the organic collagen matrix. In addition, the bone volume fraction and mechanical properties of the explanted femoral head were determined for the elderly female group. The mean SCL values of the healthy children group were significantly lower than those of the elderly women and osteogenesis imperfecta groups. For the aged women group, no significant differences were indicated in the elastic mechanical parameters, whereas bone toughness and ductility decreased significantly as the SCL increased. In conclusion, in bone collagen pathology or bone aging, the SCL is significantly impaired. This in vivo skin surface parameter can be a non-invasive tool to improve the estimation of bone matrix quality and to identify subjects at high risk of bone fracture.

A New Microarchitecture-Based Parameter to Predict the Micromechanical Properties of Bone Allografts.

Scaffolds are an essential component of bone tissue engineering. They provide support and create a physiological environment for cells to proliferate and differentiate. Bone allografts extracted from human donors are promising scaffolds due to their mechanical and structural characteristics. Bone microarchitecture is well known to be an important determinant of macroscopic mechanical properties, but its role at the microscopic, i.e., the trabeculae level is still poorly understood. The present study investigated linear correlations between microarchitectural parameters obtained from X-ray computed tomography (micro-CT) images of bone allografts, such as bone volume fraction (BV/TV), degree of anisotropy (DA), or ellipsoid factor (EF), and micromechanical parameters derived from micro-finite element calculations, such as mean axial strain (εz) and strain energy density (We). DAEF, a new parameter based on a linear combination of the two microarchitectural parameters DA and EF, showed a strong linear correlation with the bone mechanical characteristics at the microscopic scale. Our results concluded that the spatial distribution and the plate-and-rod structure of trabecular bone are the main determinants of the mechanical properties of bone at the microscopic level. The DAEF parameter could, therefore, be used as a tool to predict the level of mechanical stimulation at the local scale, a key parameter to better understand and optimize the mechanism of osteogenesis in bone tissue engineering.

Early impairment of cartilage poroelastic properties in an animal model of ACL tear.

BACKGROUND: In more than 50% of cases, anterior cruciate ligament (ACL) lesions lead to post-traumatic osteoarthritis. Ligament reconstruction stabilizes the joint, but the tear seems to impair the poroelasticity of the cartilage: synovial membrane fluid inflammation is observed 3 weeks after tearing. There have been some descriptions of visible cartilage changes, but poroelasticity has never been analyzed at this early stage. The present animal study aimed to determine (1) whether cartilage showed early poroelastic deterioration after ACL tear; (2) whether an impairment correlated with macroscopic changes; and (3) whether cartilage poroelasticity deteriorated over time. HYPOTHESIS: In the days following trauma, cartilage poroelasticity is greatly impaired, without macroscopically visible change. MATERIAL AND METHODS: ACL tear was surgically induced in 18 New-Zealand rabbits. Cartilage poroelasticity was assessed on indentation-relaxation test in 3 groups: "early", at 2 weeks postoperatively (n=6), "mid-early" at 6 weeks (n=6) and in a non-operated control group ("non-op"). Macroscopic changes were scored in the same groups. RESULTS: Poroelastic impairment was greatest at the early time-point (2 weeks). Permeability ranged from a mean 0.08±0.05×10-15 m4/Ns (range, 0.028-0.17) in the "non-op" group to 1.03±0.60×10-15 m4/Ns (range, 0.24-2.15) in the "early" group (p=0.007). Shear modulus ranged from 0.53±0.11MPa (range, 0.36-0.66) to 0.23±0.10MPa (range, 0.12-0.43), respectively (p=0.013). Macroscopic deterioration, on the other hand, differed significantly only between the "mid-early" and the "non-op" groups: p=0.011 for cartilage deterioration and p=0.008 for osteophyte formation. At the "mid-early" time point, poroelastic deterioration was less marked, with 0.33±0.33×10-15 m4/Ns permeability (range, 0.06-1.06) and shear modulus 0.30±0.10MPa (range, 0.13-0.41: respectively p=0.039 and p=0.023 compared to the "non-op" group. DISCUSSION: The severe rapid deterioration in poroelasticity following ACL tear in an animal model, as notably seen in increased permeability, corresponds to changes in cartilage microstructure, with easier outflows of interstitial fluid. This mechanical degradation may underlie onset of microcracks within the cartilage, leading to physiological loading that the cartilage by its nature is unable to repair. Further investigations are needed to correlate these experimental data with clinical findings. LEVEL OF EVIDENCE: III; comparative study with control group.

Correlation between skin and bone parameters in women with postmenopausal osteoporosis: A systematic review.

Skin and bone share similarities in terms of biochemical composition.Some authors have hypothesized that their properties could evolve concomitantly with age, allowing the estimation of the parameters of one from those of the other.We performed a systematic review of studies reporting the correlation between skin and bone parameters in women with postmenopausal osteoporosis.Fourteen studies - including 1974 patients - were included in the review.Three of these studies included two groups of participants - osteoporotic and non-osteoporotic - in order to compare skin parameters between them: two studies found a significant difference between the two groups and one did not.Eleven of these studies included one population of interest and compared its skin and bone parameters in a continuous manner: eight studies compared dermal thickness to bone mineral density (seven found a significant correlation [R = 0.19-0.486] and one did not); two studies compared skin elasticity to bone mineral density (both found a significant correlation [R = 0.44-0.57); and one study compared skin collagen to bone mineral density and found a significant correlation (R = 0.587).It can be assumed that the estimation of skin alterations from ageing could help in estimating concomitant bone alterations. Cite this article: EFORT Open Rev 2018;3:449-460. DOI: 10.1302/2058-5241.3.160088.

Mechanical alterations of the bone-cartilage unit in a rabbit model of early osteoarthrosis.

OBJECTIVE: The purpose of this study was to assess mechanical properties along with microstructural modifications of the hyaline cartilage (HC), calcified cartilage (CC) and cortical plate (Ct.Pt), in an anterior cruciate ligament transection (ACLT) model. Medial femoral condyles of six healthy rabbits (control group) and of six ACLT rabbits 6 weeks after OA induction were explanted. The zone of interest (ZOI) for all experiments was defined as the weight bearing areas of the samples. Biomechanical properties were measured using nanoindentation and morphological changes were evaluated using biphotonic confocal microscopy (BCM). RESULTS: All rabbits of the ACLT group displayed early PTOA. The results indicate an overall decrease in the mechanical properties of the HC, CC and Ct.Pt in the ACLT group. The average equilibrium modulus and elastic fraction of the HC decreased by 42% and 35%, respectively, compared with control group. The elastic moduli of the CC and Ct.Pt decreased by 37% and 16%, respectively, compared with control group. A stiffness gradient between CC and Ct.Pt appeared in the ACLT group. The irregularity of the cement line, quantified by its tortuosity in BCM images, was accentuated in the ACLT group compared with the control group. CONCLUSIONS: In the ACLT model, weight-bearing stress was modified in the ZOI. This disruption of the stress pattern induced alterations of the tissues composing the bone-cartilage unit. In term of mechanical properties, all tissues exhibited changes. The most affected tissue was the most superficial: hyaline cartilage displayed the strongest relative decrease (42%) followed by calcified cartilage (37%) and cortical plate was slightly modified (16%). This supports the hypotheses that PTOA initiates in the hyaline cartilage.

Characterization of the anisotropic mechanical behavior of human abdominal wall connective tissues.

Abdominal wall sheathing tissues are commonly involved in hernia formation. However, there is very limited work studying mechanics of all tissues from the same donor which prevents a complete understanding of the abdominal wall behavior and the differences in these tissues. The aim of this study was to investigate the differences between the mechanical properties of the linea alba and the anterior and posterior rectus sheaths from a macroscopic point of view. Eight full-thickness human anterior abdominal walls of both genders were collected and longitudinal and transverse samples were harvested from the three sheathing connective tissues. The total of 398 uniaxial tensile tests was conducted and the mechanical characteristics of the behavior (tangent rigidities for small and large deformations) were determined. Statistical comparisons highlighted heterogeneity and non-linearity in behavior of the three tissues under both small and large deformations. High anisotropy was observed under small and large deformations with higher stress in the transverse direction. Variabilities in the mechanical properties of the linea alba according to the gender and location were also identified. Finally, data dispersion correlated with microstructure revealed that macroscopic characterization is not sufficient to fully describe behavior. Microstructure consideration is needed. These results provide a better understanding of the mechanical behavior of the abdominal wall sheathing tissues as well as the directions for microstructure-based constitutive model.

Contra-lateral hip fracture in the elderly: are decreased body mass index and skin thickness predictive factors?

PURPOSE: A correlation between soft tissue thickness and osteoporosis has been suggested. We aimed to estimate if a low body mass index (BMI) and/or a decrease of skin thickness could estimate the risk of contra-lateral hip fracture. METHODS: First, we performed a retrospective analysis of 1268 patients treated for a hip fracture. The 146 patients who had a contra-lateral hip fractures-study group-were compared with the 1078 patients who did not-control group. Four BMI categories were considered: obese, overweight, normal weight and low weight. Second, we enrolled prospectively 1000 consecutive patients in the emergency department. History of fractures, BMI, and skin aspect on the dorsum of both hands-classified as severe decrease thickness, moderate decrease thickness or normal-were recorded. RESULTS: pt?>In the first part, we found that patients with contra-lateral fractures had a significantly lower BMI than those in the control group (22.2 Vs 26.5 kg/m2, p = 0.01). In the second part, 48 on 1000 patients had a hip fracture. Among them, six had a contra-lateral fracture. BMI was 23.4 kg/m2 in bilateral hip fractures, 33.68 kg/m2 in the unilateral fracture group, and 28.04 kg/m2 in the non-fracture group (p = 0.04). Finally, patients with contra-lateral hip fractures had a severe decrease thickness of the skin. CONCLUSION: A low BMI and a decreased skin thickness increase independently the risk of fractures by three times. When associated, they increase the risk of fracture risk by five times. This combination had a sensitivity at 71 % and a specificity at 90 % for predicting hip fracture.

Predictive model for tensile strength of pharmaceutical tablets based on local hardness measurements.

In the pharmaceutical field, tablets are the most common dosage forms for oral administration. During the manufacture of tablets, measures are taken to assure that they possess a suitable mechanical strength to avoid crumbling or breaking when handling while ensuring disintegration after administration. Accordingly, the tensile strength is an essential parameter to consider. In the present study, microscopic hardness and macroscopic tensile strength of binary tablets made from microcrystalline cellulose and caffeine in various proportions were measured. A relationship between these two mechanical properties was found for binary mixture. The proposed model was based on two physical measurements easily reachable: hardness and tablet density. Constants were determined from the two extreme compositions of this given system. This model was validated with experimental results, and a comparison was made with the one developed by Wu et al. (2005). Both models are relevant for this studied system. Nonetheless, with this model, the tablet tensile strength can be connected with a tablet characteristic at microscopic scale in which porosity is not needed.

Microstructure and compressive mechanical properties of cortical bone in children with osteogenesis imperfecta treated with bisphosphonates compared with healthy children.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by a change in bone tissue quality, but little data are available to describe the factors involved at the macroscopic scale. To better understand the effect of microstructure alterations on the mechanical properties at the sample scale, we studied the structural and mechanical properties of six cortical bone samples from children with OI treated with bisphosphonates and compared them to the properties of three controls. Scanning electron microscopy, high resolution computed tomography and compression testing were used to assess these properties. More resorption cavities and a higher osteocyte lacunar density were observed in OI bone compared with controls. Moreover, a higher porosity was measured for OI bones along with lower macroscopic Young's modulus, yield stress and ultimate stress. The microstructure was impaired in OI bones; the higher porosity and osteocyte lacunar density negatively impacted the mechanical properties and made the bone more prone to fracture.

Numerical Study of Granular Scaffold Efficiency to Convert Fluid Flow into Mechanical Stimulation in Bone Tissue Engineering.

Controlling the mechanical environment in bioreactors represents a key element in the reactors' optimization. Positive effects of fluid flow in three-dimensional bioreactors have been observed, but local stresses at cell scale remain unknown. These effects led to the development of numerical tools to assess the micromechanical environment of cells in bioreactors. Recently, new possible scaffold geometry has emerged: granular packings. In the present study, the primary goal was to compare the efficiency of such a scaffold to the other ones from literature in terms of wall shear stress levels and distributions. To that aim, three different types of granular packings were generated through discrete element method, and computational fluid dynamics was used to simulate the flow within these packings. Shear stress levels and distributions were determined. A linear relationship between shear stress and inlet velocity was observed, and its slope was similar to published data. The distributions of normalized stress were independent of the inlet velocity and were highly comparable to those of widely used porous scaffolds. Granular packings present similar features to more classical porous scaffolds and have the advantage of being easy to manipulate and seed. The methods of this work are generalizable to the study of other granular packing configurations.

Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength.

Digital image correlation of bone sequential microscopic observations.

A method of image correlation is presented to study sequential microscopic observations of human Haversian cortical bone. Imaging biological tissues is sometimes challenging owing to their complex microstructures in particular when microcracks appear. Bone microfractures can be studied in micro compression tests where the progressive growth of small cracks is imaged by light microscopy. The two-dimensional displacement field on the sample surface is then tracked by various digital image correlation methods based on cross-correlation formulation. Because of the potential high number of sequential observations, the method calculates the displacements at given growth steps obtained either by direct comparison of the studied step and the undeformed initial state, called 'direct correlation', or by iterative comparisons of successive pairs of observations, called 'gradual correlation'. In the gradual procedure, two cases are studied, referred to as 'invariant gradual correlation' and 'varying gradual correlation', when the correlation domain is transferred till the last observation or reinitialised for each image pairs. As bone is highly heterogeneous, two types of correlation procedures are considered with or without domain partition (WDP or WODP) delimiting material and strong discontinuities. The precision of the methods is specifically evaluated for experimental observations.