Objective Spectroscopic techniques, such as near-infrared (NIR) spectroscopy, are gaining significant research interest for characterizing connective tissues, particularly articular cartilage, because there is still a largely unmet need for rapid, accurate and objective methods for assessing tissue integrity in real-time during arthroscopic surgery. This study aims to identify the NIR spectral range that is optimal for characterizing cartilage integrity by (a) identifying the contribution of its major constituents (collagen and proteoglycans) to its overall spectrum using proxy constituent models and (b) determining constituent-specific spectral contributions that can be used for assessment of cartilage in its physiological state. Design The NIR spectra of cartilage matrix constituent models were measured and compared with specific molecular components of organic compounds in the NIR spectral range in order to identify their bands and molecular assignments. To verify the identified bands, spectra of the model compounds were compared with those of native cartilage. Since water obscures some bands in the NIR range, spectral measurements of the native cartilage were conducted under conditions of decreasing water content to amplify features of the solid matrix components. The identified spectral bands were then compared and examined in the resulting spectra of the intact cartilage samples. Results As water was progressively eliminated from cartilage, the specific contribution of the different matrix components was observed to correspond with those identified from the proxy cartilage component models. Conclusion Spectral peaks in the regions 5500 to 6250 cm(-1) and 8100 to 8600 cm(-1) were identified to be effective for characterizing cartilage proteoglycan and collagen contents, respectively.

The conventional mechanical properties of articular cartilage, such as compressive stiffness, have been shown to have limited capacity to distinguish visually normal from degraded cartilage samples. In this study, a new mechanical indentation framework for assessing functional properties of articular cartilage during loading/unloading, i.e. deformation and recovery, was established. The capacity of a ring-shaped indenter integrated with an ultrasound transducer to distinguish mechanically intact from proteoglycan-depleted tissue was investigated. To achieve this, normal and enzymatically degraded bovine osteochondral samples were subjected to loading/unloading while the response of the tissue at the middle was captured by ultrasound at the same time. The enzymatic degradation model was characterized by amount of proteoglycan content, glycosaminoglycan release and proteomic analysis. The mechanical response of a wider continuum of articular cartilage in the loaded area and its surrounding region was captured in this framework leading to investigate two parameters, L and TS, related to the surrounding tissue of the loaded area for functional assessment of cartilage. L is the distance between the ultrasound transducer and articular cartilage surface and TS is the transient strain of articular cartilage during loading and unloading. Classification Analysis based on Principal Component Analysis was used to investigate the capacity of the new parameters to assess the functionality of the tissue. Multivariate statistics based on Partial Least Squares regression was employed to identify the correlation between the response of the tissue in the indented area and its surrounding cartilage. The results of this study indicate that L during loading (deformation) can differentiate normal and mildly proteoglycan-depleted samples from severely depleted samples and L during unloading (recovery) can distinguish between normal and proteoglycan-depleted tissue. However, TS during deformation and recovery is unable to discriminate normal cartilage samples from proteoglycan-depleted tissue. The results also demonstrate a strong correlation between mechanical properties of the loaded area with the response of its surrounding cartilage during recovery. It is therefore concluded that L in this newly established framework can discriminate between normal and proteoglycan-depleted cartilage samples. However, more samples will be needed to verify the demarcation between samples degraded for varying amount of time.

Background: Histological evaluation of articular cartilage, such as using the Mankin scoring system, is the gold standard for characterization of tissue integrity. This scoring system takes into account several parameters indicative of the tissue's health; however, the collagen integrity, which is a primary indicator of cartilage health is not taken into consideration. Thus, there is need to enhance histological grading of articular cartilage by incorporating explicit scoring of collagen degeneration into the Modified Mankin grading system. This paper explores a new histological grading parameter for collagen network degradation and how this information can be used to augment a widely used grading scheme like the Modified Mankin grading system. Methods: Intact and degenerated human cartilage were examined histologically and then subjected to second harmonic generation imaging, leading to qualitative and quantitative description of collagen disruption emanating from the surface to subsurface layers of the tissue. This data was then incorporated into the Modified Mankin grading system. Findings: Second harmonic generation image analysis reveals a relationship between changes in collagen architecture and histologically observed tissue disruption in degenerated articular cartilage. Interpretation: Histological tissue disruption in degenerated human articular cartilage is directly related to the reorganization of collagen fibrils in the form of intense fibril aggregation, either as a result of degeneration or aging. This method of mapping disrupted tissue regions to quantitative collagen fibril damage can be coded into cartilage grading systems and could inform clinical practice and scientific research.

Collagen meshwork, proteoglycans and fluid are the three main components in articular cartilage type II. They have been commonly simulated indirectly via Young’s modulus in loads of numerical studies recently in which collagen meshwork and proteoglycans are mainly responsible the dynamic compressive, tensile response and the static (equilibrium) compressive stiffness respectively while fluid plays a significant role of the transient viscoelastic creep and stress-relaxation behavior of the matrix. In this paper, a new approach is presented in which the three components create a 3-D arrangement of interwoven osmotic units. Based on the physical model of the cartilage structure (Broom ND, Marra DL (1985) New structure concepts of articular cartilage demonstrated with a physica model. Connect Tissue Res 14:18 [2]), osmotic units are arranged as the 3D-matrix of voxels i.e. cells including histological information. In order to do so, in this paper, the osmotic configuration with the collagen-proteoglycans entrapment architecture can be represented by the system of balloon-string. Each voxel contains the concentrations of collagen, proteoglycans and water obtained from the histological experiments. Thus osmotic pressure and distension at each osmotic unit can be computed based on these concentrations. This simulation allows to setup a new model of articular cartilage in which fluid flow is described and calculated without physical formulas, that is able to probe and study fluid and associated matrix pressures and deliver insight into the advection of pressures, diffusion and exudation of fluid, and solutes within loaded cartilage. Therefore, a new model of articular cartilage is ready to create based on the new approach of the osmotic component.

Single-phase porous materials contain multiple components that intermingle up to the ultramicroscopic level. Although the structures of the porous materials have been simulated with agent-based methods, the results of the available methods continue to provide patterns of distinguishable solid and fluid agents which do not represent materials with indistinguishable phases. This paper introduces a new agent (hybrid agent) and category of rules (intra-agent rule) that can be used to create emergent structures that would more accurately represent single-phase structures and materials. The novel hybrid agent carries the characteristics of system’s elements and it is capable of changing within itself, while also responding to its neighbours as they also change. As an example, the hybrid agent under one-dimensional cellular automata formalism in a two-dimensional domain is used to generate patterns that demonstrate the striking morphological and characteristic similarities with the porous saturated single-phase structures where each agent of the “structure” carries semi-permeability property and consists of both fluid and solid in space and at all times. We conclude that the ability of the hybrid agent to change locally provides an enhanced protocol to simulate complex porous structures such as biological tissues which could facilitate models for agent-based techniques and numerical methods.

Nanotextured surfaces (NTSs) are critical to organisms as self-adaptation and survival tools. These NTSs have been actively mimicked in the process of developing bactericidal surfaces for diverse biomedical and hygiene applications. To design and fabricate bactericidal topographies effectively for various applications, understanding the bactericidal mechanism of NTS in nature is essential. The current mechanistic explanations on natural bactericidal activity of nanopillars have not utilized recent advances in microscopy to study the natural interaction. This research reveals the natural bactericidal interaction between E. coli and a dragonfly wing's (Orthetrum villosovittatum) NTS using advanced microscopy techniques and proposes a model. Contrary to the existing mechanistic models, this experimental approach demonstrated that the NTS of Orthetrum villosovittatum dragonfly wings has two prominent nanopillar populations and the resolved interface shows membrane damage occurred without direct contact of the bacterial cell membrane with the nanopillars. We propose that the bacterial membrane damage is initiated by a combination of strong adhesion between nanopillars and bacterium EPS layer as well as shear force when immobilized bacterium attempts to move on the NTS. These findings could help guide the design of novel biomimetic nanomaterials by maximizing the synergies between biochemical and mechanical bactericidal effects.

The use of porous cellular structures in bone tissue engineering can provide mechanical and biological environments closer to the host bone. However, poor internal architectural designs may lead to catastrophic failure. In this work, 192 open-porous cellular structures were fabricated using 3D printing (3DP) techniques. The mechanical and biological behavior of four 3D internal structures (octahedral, pillar octahedral, cubic and truncated octahedral) was investigated. It was found that the pillar octahedral shape has not only greater stiffness and strength under compression, shear and torsion but increased rate of pre-osteoblastic cell proliferation. We believe bone implants can be fabricated using 3DP techniques and their mechanical and biological performance can be tailored by modifying the internal architectures.

We demonstrate in this study the potential of near infrared (NIR) spectroscopy as a tool for monitoring progression of cartilage degeneration in an animal model. Osteoarthritic degeneration was artificially induced in one joint in laboratory rats, and the animals were sacrificed at four time points: 1, 2, 4, and 6 weeks (3 animals/week). NIR spectra were acquired from both (injured and intact) knees. Subsequently, the joint samples were subjected to histological evaluation and glycosaminoglycan (GAG) content analysis, to assess disease severity based on the Mankin scoring system and to determine proteoglycan loss, respectively. Multivariate spectral techniques were then employed for classification (principal component analysis and support vector machines) and prediction (partial least squares regression) of the samples’ Mankin scores and GAG content from their NIR spectra. Our results demonstrate that NIR spectroscopy is sensitive to degenerative changes in articular cartilage, and is capable of distinguishing between mild (weeks 1&2; Mankin <=2) and advanced (weeks 4&6; Mankin =>3) cartilage degeneration. In addition, the spectral data contains information that enables estimation of the tissue’s Mankin score (error = 12.6%, R2 = 86.2%) and GAG content (error = 7.6%, R2 = 95%). We conclude that NIR spectroscopy is a viable tool for assessing cartilage degeneration post-injury, such as, post-traumatic osteoarthritis.

The incapability of controlling relative micromotions and load transfers to a peri-prosthetic femur shortens implant longevity. This study aims to evaluate the possibility of applying graded porous cobalt chromium (CoCr) to cementless femoral stems. 3D finite element analyses and physical testings of hip implants were conducted with four different grading orientations, along the axial and radial planes of the femoral stem. The results show that the CoCr graded femoral stems with a porosity decreased caudally and inwardly may control the relative micromotions in an acceptable range for bone ingrowth, significantly increase stress transfers on the Gruen zone 1 and 7, and attain the flexural stiffness comparable to human femurs. Therefore, CoCr graded femoral stems demonstrate great potential for applications in implants with reduced stress shielding and improved long-term survival rates.

The use of cobalt chromium (CoCr) in orthopaedic joint replacement shields the peri-implant bone stress, contributing to a premature loosening of the implants. In order to reduce the need for revision surgeries, light weight implants with tailored functionalities need to be developed. In this study, the compressive mechanical properties of laser-melted CoCr cellular structures with a pillar octahedral architecture [0°±45°] were investigated. Four types of graded cellular structures, based on grading orientations along radial and longitudinal planes, were manufactured using selective laser melting techniques. The cellular structures in this study have the mechanical properties (E=2.3–3.1GPa, σ=113–523MPa) compatible with bone structures. Grading a porosity of the CoCr cellular structures provides a greater stress transfer to the proximal peri-implant area. The axially graded cellular structures demonstrated significant reduction of the peri-implant stress shielding. Incorporation of CoCr graded cellular structures into a structure like femoral stems is expected to have the potential to reduce the revision surgeries.

Collecting functional quantitative intra matrix data in experimental samples of articular cartilage is still challenging due to its delicate complex heterogeneous structure in which constituents are intermingled right up to the ultramicroscopic level. Any attempt to insert a transducer inside this material via piercing would damage the structure leading to unrepresentative data. Traditional non-invasive methods are technically difficult for obtaining precise functional data. This paper presents a novel computational approach, using the agentbased concept, to create a ‘virtual microscope’ that can be used to provide functional information throughout a heterogeneous complex medium, such as articular cartilage, in silico. The method involves two-dimensional cellular automata, a hybrid agent, new local agent rule and a traditional neighbourhood rule. The hybrid agent combines constituents of the system (solid and fluid) where the local rule determines intra-agent evolution. The proposed approach was validated by simulating diffusion into a model of cartilage matrix that was characterized with anisotropic permeability. The simulated results were then compared to magnetic resonance imaging (MRI) data. Spatial map of diffusion at different times and depthdependent diffusion profiles were provided in colour-coded pictures. Qualitative and quantitative comparison of results with experimental data shows that this novel approach can accurately and efficiently represent diffusion of fluid into the cartilage matrix. It demonstrates the potential of hybrid agent and local rule to enhance agent-based techniques for porous materials and other areas of research. We conclude that the ability to establish a “virtual microscope” offers a viable opportunity for in-silico experiments that can extend our knowledge beyond the capability of traditional laboratory experiments, while also facilitating information for creating models for numerical methods such as finite element analysis, meshless and smoothed particle hydrodynamics. The combination of the approach presented here with conventional simulation methods can provide a framework for modelling and analysis of complex porous materials. We concluded that the hybrid agent and local rule concept introduced in this paper can also be potentially exploited to enhance many of the existing agent-based techniques.

Interfragmentary movement (IFM) at the fracture site plays an important role in fracture healing, particularly during its early stage, via influencing the mechanical microenvironment of mesenchymal stem cells within the fracture callus. However, the effect of changes in IFM resulting from the changes in the configuration of locking plate fixation on cell differentiation has not yet been fully understood. In this study, mechanical experiments on surrogate tibia specimens, manufactured from specially formulated polyurethane, were conducted to investigate changes in IFM of fractures under various locking plate fixation configurations and loading magnitudes. The effect of the observed IFM on callus cell differentiation was then further studied using computational simulation. We found that during the early stage, cell differentiation in the fracture callus is highly influenced by fracture gap size and IFM, which in turn, is highly sensitive to locking plate fixation configuration. The computational model predicted that a small gap size (e.g. 1 mm) under a relatively flexible configuration of locking plate fixation (larger bone-plate distances and working lengths) could experience excessive strain and fluid flow within the fracture site, resulting in excessive fibrous tissue differentiation and delayed healing. By contrast, a relatively flexible configuration of locking plate fixation was predicted to improve cartilaginous callus formation and bone healing for a relatively larger gap size (e.g. 3 mm). If further confirmed by animal and human studies, the research outcome of this paper may have implications for orthopaedic surgeons in optimising the application of locking plate fixations for fractures in clinical practice.

In this study, the authors examine the influence of joint chemical environment by measuring changes in the tribological properties (friction coefficient and charge density) of contacting surfaces of normal and degenerated cartilage samples in bath solutions of varying pH (2.0–9.0). Bovine articular cartilage samples (n = 54) were subjected to several surface measurements, including interfacial energy, contact angle, and friction coefficient, at varying pH. The samples were delipidized and then subjected to the same measurement protocols. Our results reveal that the interfacial energy and charge density, which have been shown to be related to friction coefficient, decrease with pH in the acidic range and approach constant values at physiological (or synovial fluid) pH of 7.4 and beyond it, i.e., toward basic pH domain. The authors conclude that this rather complex response explains the long-term efficacy with respect to ageing and associated pH changes, of the phospholipid layers that facilitate the almost frictionless, hydration–lubrication involving contact in the mammalian musculoskeletal system.

Objectives: In this study, we examine the capacity of a new parameter, based on the recovery response of articular cartilage, to distinguish between healthy and damaged tissues. We also investigate whether or not this new parameter correlates with the near-infrared (NIR) optical response of articular cartilage. Design: Normal and artificially degenerated (proteoglycan-depleted) bovine cartilage samples were nondestructively probed using NIR spectroscopy. Subsequently they were subjected to a load and unloading protocol, and the recovery response was logged during unloading. The recovery parameter, elastic rebound (ER), is based on the strain energy released as the samples underwent instantaneous elastic recovery. Results: Our results reveal positive relationship between the rebound parameter and cartilage proteoglycan content (normal samples: 2.20 ± 0.10 N mm; proteoglycan-depleted samples: 0.50 ± 0.04 N mm for 1 hour of enzymatic treatment and 0.13 ± 0.02 N mm for 4 hours of enzymatic treatment). In addition, multivariate analysis using partial least squares regression was employed to investigate the relationship between ER and NIR spectral data. The results reveal significantly high correlation (R2cal = 98.35% and R2val = 79.87%; P < 0.0001), with relatively low error (14%), between the recovery and optical response of cartilage in the combined NIR regions 5,450 to 6,100 cm−1 and 7,500 to 12,500 cm−1. Conclusion: We conclude that ER can indicate the mechanical condition and state of health of articular cartilage. The correlation of ER with cartilage optical response in the NIR range could facilitate real-time evaluation of the tissue’s integrity during arthroscopic surgery and could also provide an important tool for cartilage assessment in tissue engineering and regeneration research.

This review describes recent developments and applications of near-infrared (NIR) spectroscopy for characterization of articular cartilage integrity. It summarizes the research findings in this area and presents some spectral ranges and peaks associated with the different properties and components of articular cartilage. We further describe recent adaptations of NIR spectroscopy for clinical evaluation of articular cartilage injury and degeneration. Critical to accurate decision-making during repair surgery is having clear knowledge of lesion severity and spread, and how to grade the quality of surrounding cartilage. Thus, in this review, we detail efforts aimed at quantification and classification of cartilage pathology using NIR spectroscopy. Finally, we present open questions and challenges with a view to guiding future directions in NIR spectroscopy research on articular cartilage.

Standard single-stage tooth-to-pin-contact Cycloidal drives deliver various benefits such as high-ratio speed reduction, highly efficient torque delivery, compact physical structure etc. They lack torsional rigidity on their own because of inherent “lost-motion” and “backlash”, and hence inappropriate for precision-motion mechanical systems. However from dynamics point of view, this is beneficial for non-precision-motion systems, as it reduces the drive-train's shock factor. Currently there are no design standards for Cycloidal drives owing to their complicated component stiffness behaviour, increased tooth-load-sharing at overloads etc., which further obscures the analytical estimation of torsional rigidity of a given configuration. This paper presents a novel method comprising both analytical and numerical techniques for the effective determination of the elastic torsional compliance of single-stage Cycloidal drives based on static experimental results conducted on a commercially available gear-drive. We establish a unique key parameter −ηOP, ‘torque transfer efficiency’, of output-shaft-pins from mechanism-kinematics to be included in the system's dynamic model. Applying the techniques and outcomes presented here in a lumped mass/inertia dynamic model yielded agreeable natural frequency of torsional oscillations in comparison to experimental results obtained under the same loading conditions. This can lead to dynamically optimised designs and hence their standardisation.

It has been demonstrated that most cells of the body respond to osmotic pressure in a systematic manner. The disruption of the collagen network in the early stages of osteoarthritis causes an increase in water content of cartilage which leads to a reduction of pericellular osmolality in chondrocytes distributed within the extracellular environment. It is therefore arguable that an insight into the mechanical properties of chondrocytes under varying osmotic pressure would provide a better understanding of chondrocyte mechanotransduction and potentially contribute to knowledge on cartilage degeneration. In this present study, the chondrocyte cells were exposed to solutions with different osmolality. Changes in their dimensions and mechanical properties were measured over time. Atomic force microscopy (AFM) was used to apply load at various strain-rates and the force–time curves were logged. The thin-layer elastic model was used to extract the elastic stiffness of chondrocytes at different strain-rates and at different solution osmolality. In addition, the porohyperelastic (PHE) model was used to investigate the strain-rate-dependent responses under the loading and osmotic pressure conditions. The results revealed that the hypo-osmotic external environment increased chondrocyte dimensions and reduced Young’s modulus of the cells at all strain-rates tested. In contrast, the hyper-osmotic external environment reduced dimensions and increased Young’s modulus. Moreover, using the PHE model coupled with inverse FEA simulation, we established that the hydraulic permeability of chondrocytes increased with decreasing extracellular osmolality which is consistent with previous work in the literature. This could be due to a higher intracellular fluid volume fraction with lower osmolality.

Besides the elastic stiffness, the relaxation behavior of single living cells is also of interest of various researchers when studying cell mechanics. It is hypothesized that the relaxation response of the cells is governed by both intrinsic viscoelasticity of the solid phase and fluid-solid interactions mechanisms. There are a number of mechanical models have been developed to investigate the relaxation behavior of single cells. However, there is lack of model enable to accurately capture both of the mechanisms. Therefore, in this study, the porohyperelastic (PHE) model, which is an extension of the consolidation theory, combined with inverse Finite Element Analysis (FEA) technique was used at the first time to investigate the relaxation response of living chondrocytes. This model was also utilized to study the dependence of relaxation behavior of the cells on strain-rates. The stress-relaxation experiments under the various strain-rates were conducted with the Atomic Force Microscopy (AFM). The results have demonstrated that the PHE model could effectively capture the stress-relaxation behavior of the living chondrocytes, especially at intermediate to high strain-rates. Although this model gave some errors at lower strain-rates, its performance was acceptable. Therefore, the PHE model is properly a promising model for single cell mechanics studies. Moreover, it has been found that the hydraulic permeability of living chondrocytes reduced with decreasing of strain-rates. It might be due to the intracellular fluid volume fraction and the fluid pore pressure gradients of chondrocytes were higher when higher strain-rates applied.