ACL transection results in a posterior shift and increased velocity of contact on the medial tibial plateau.

Our objective was to quantify the effect of ACL transection on dynamic knee joint contact force distributions during simulated gait. Given the prevalence of medial compartment osteoarthritis in un-reconstructed ACL ruptured knees, we hypothesized that changes in contact mechanics after ACL transection would be most prevalent in the medial compartment. Twelve human cadaveric knees were tested using a dynamic knee gait simulator which was programmed to mimic a clinical Lachman exam and gait.

Effect of Articular Surface Compression on Cartilage Extracellular Matrix Deformation.

Early stage osteoarthritis is characterized by disruption of the superficial zone (SZ) of articular cartilage, including collagen damage and proteoglycan loss, resulting in "mechanical softening" of the extracellular matrix (ECM). The role of the SZ in controlling fluid exudation and imbibition during loading and unloading, respectively, was studied using confined creep compression tests. Bovine osteochondral (OC) plugs were subjected to either a static (88 kPa) or cyclic (0-125 kPa at 1 Hz) compressive stress for five minutes, and the cartilage deformation and recovery were measured during tissue loading and unloading, respectively.

Squeeze-film properties of synovial fluid and hyaluronate-based viscosupplements.

The rheological properties of synovial fluid and hyaluronate (HA) solutions have been studied using a variety of viscometers and rheometers. These devices measure the viscosity of the fluid's resistance to shearing forces, which is useful when studying the lubrication and frictional properties of movable joints. Less commonly used is a squeeze-film fluid test, mechanistically similar to when two joint surfaces squeeze interposed fluid.

Collagen peptide simulated bending after applied axial deformation.

Structural proteins in the extracellular matrix are subjected to a range of mechanical loading conditions, including varied directions of force application. Molecular modeling suggests that these mechanical forces directly affect collagen's conformation and the subsequent mechanical response at the molecular level is complex. For example, tensile forces in the axial direction result in collagen triple helix elongation and unwinding, while perpendicular forces can cause local triple helix disruption.

Ultraviolet light (365 nm) transmission properties of articular cartilage as a function of depth, extracellular matrix, and swelling.

Current tissue engineering approaches for treatment of injured or diseased articular cartilage use ultraviolet light (UV) for in situ photopolymerization of biomaterials to fill chondral and osteochondral defects as well as resurfacing, stiffening and bonding the extracellular matrix and tissue interfaces. The most commonly used UV light wavelength is UVA 365 nm, the least cytotoxic and deepest penetrating. However, little information is available on the transmission of UVA 365 nm light through the cartilage matrix.

Effect of interface mechanical discontinuities on scaffold-cartilage integration.

A consistent lack of lateral integration between scaffolds and adjacent articular cartilage has been exhibited in vitro and in vivo. Given the mismatch in mechanical properties between scaffolds and articular cartilage, the mechanical discontinuity that occurs at the interface has been implicated as a key factor, but remains inadequately studied. Our objective was to investigate how the mechanical environment within a mechanically loaded scaffold-cartilage construct might affect integration.

Articular cartilage response to a sliding load using two different-sized spherical indenters1.

Background: Cartilage surface contact geometry influences the deformational behavior and stress distribution throughout the extracellular matrix (ECM) under load.

Objective: To test the correlation between the mechanical and cellular response of articular cartilage when loaded with two different-sized spherical indenters under dynamic reciprocating sliding motion.

Methods: Articular cartilage explants were subjected to a reciprocating sliding load using a 17.

Influence of the pericellular and extracellular matrix structural properties on chondrocyte mechanics.

Understanding the mechanical factors that drive the biological responses of chondrocytes is central to our interpretation of the cascade of events that lead to osteoarthritic changes in articular cartilage. Chondrocyte mechanics is complicated by changes in tissue properties that can occur as osteoarthritis (OA) progresses and by the interaction between macro-scale, tissue level, properties, and micro-scale pericellular matrix (PCM) and local extracellular matrix (ECM) properties, both of which cannot be easily studied using in vitro systems. Our objective was to study the influence of macro- and micro-scale OA-associated structural changes on chondrocyte strains.

Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

Objective: Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers.

Photocrosslinked tyramine-substituted hyaluronate hydrogels with tunable mechanical properties improve immediate tissue-hydrogel interfacial strength in articular cartilage.

Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage.

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads.

In physiological conditions, joint function involves continuously moving contact areas over the tissue surface. Such moving contacts play an important role for the durability of the tissue. It is known that in pathological joints these motion paths and contact mechanics change.

Use of novel chitosan hydrogels for chemical tissue bonding of autologous chondral transplants.

The objective of this study was to evaluate the effect of chemical tissue bonding (CTB) on adhesion strength, fluid permeability, and cell viability across a cartilaginous graft-host interface in an in vitro autologous chondral transplant (ACT) model. Chitosan-based cross-linkers; Chitosan-Rose Bengal [Chi-RB (Ch-ABC)], Chitosan-Genipin [Chi-GP (Ch-ABC)], and Chitosan-Rose Bengal-Genipin [Chi-RB-GP (Ch-ABC)] were applied to bovine immature cartilage explants after pre-treatment with surface degrading enzyme, Chondroitinase-ABC (Ch-ABC). Adhesion strength, fluid permeability and cell viability were assessed via mechanical push-out shear testing, fluid transport and live/dead cell staining, respectively.

Shape of chondrocytes within articular cartilage affects the solid but not the fluid microenvironment under unconfined compression.

Unlabelled: Metabolic activity of the chondrocytes in articular cartilage is strongly related to their zone-specific shape and the composition and mechanical properties of their surrounding extracellular matrix (ECM). However the mechanisms by which cell shape influences the response of the ECM microenvironment to mechanical loading is yet to be elucidated. This relationship was studied using a biphasic multiscale finite element model of different shaped chondrocytes in the superficial and deep zones of the ECM during unconfined stress relaxation.

Mechanical Loading of Cartilage Explants with Compression and Sliding Motion Modulates Gene Expression of Lubricin and Catabolic Enzymes.

Objective: Translation of the contact zone in articulating joints is an important component of joint kinematics, yet rarely investigated in a biological context. This study was designed to investigate how sliding contact areas affect cartilage mechanobiology. We hypothesized that higher sliding speeds would lead to increased extracellular matrix mechanical stress and the expression of catabolic genes.

Resurfacing damaged articular cartilage to restore compressive properties.

Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation.

A biphasic finite element study on the role of the articular cartilage superficial zone in confined compression.

The aim of this study was to investigate the role of the superficial zone on the mechanical behavior of articular cartilage. Confined compression of articular cartilage was modeled using a biphasic finite element analysis to calculate the one-dimensional deformation of the extracellular matrix (ECM) and movement of the interstitial fluid through the ECM and articular surface. The articular cartilage was modeled as an inhomogeneous, nonlinear hyperelastic biphasic material with depth and strain-dependent material properties.

A biphasic multiscale study of the mechanical microenvironment of chondrocytes within articular cartilage under unconfined compression.

Computational analyses have been used to study the biomechanical microenvironment of the chondrocyte that cannot be assessed by in vitro experimental studies; yet all computational studies thus far have focused on the effect of zonal location (superficial, middle, and deep) on the mechanical microenvironment of chondrocytes. The aim of this paper was to study the effect of both zonal and radial locations on the biomechanical microenvironment of chondrocytes in inhomogeneous cartilage under unconfined stress relaxation. A biphasic multiscale approach was employed and nine chondrocytes in different locations were studied.

An in vitro model for the pathological degradation of articular cartilage in osteoarthritis.

The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests.

Glycation cross-linking induced mechanical-enzymatic cleavage of microscale tendon fibers.

Recent molecular modeling data using collagen peptides predicted that mechanical force transmitted through intermolecular cross-links resulted in collagen triple helix unwinding. These simulations further predicted that this unwinding, referred to as triple helical microunfolding, occurred at forces well below canonical collagen damage mechanisms. Based in large part on these data, we hypothesized that mechanical loading of glycation cross-linked tendon microfibers would result in accelerated collagenolytic enzyme damage.

Role of coracoacromial ligament and related structures in glenohumeral stability: a cadaveric study.

This study sought to determine the role of the coracoacromial ligament and related arch structures in glenohumeral joint stabilization. Eight fresh-frozen cadaver specimens were tested at multiple angles of glenohumeral abduction and rotation for translations (in the direction of and perpendicular to a 50-N force) in intact, vented shoulders and after three interventions: coracoacromial veil release, coracoacromial ligament release, and anterior acromioplasty. After releasing the veil, an inferior force significantly increased inferior translation at lower angles of abduction with no additional increase after coracoacromial ligament section or acromioplasty.

A Comparative Study of Fibronectin Cleavage by MMP-1, -3, -13, and -14.

Fibronectin fragments are important for synovial inflammation and the progression of arthritis, and thus, identifying potential enzymatic pathways that generate these fragments is of vital importance. The objective of this study was to determine the cleavage efficiency of fibronectin by matrix metalloproteinases (MMP-1, MMP-3, MMP-13, and MMP-14). Intact human plasma fibronectin was co-incubated with activated MMPs in neutral or acidic pH for up to 24 hours at 37 °C.

A novel device to apply controlled flexion and extension to the rat knee following anterior cruciate ligament reconstruction.

We designed and validated a novel device for applying flexion-extension cycles to a rat knee in an in vivo model of anterior cruciate ligament reconstruction (ACL-R). Our device is intended to simulate rehabilitation motion and exercise post ACL-R to optimize physical rehabilitation treatments for the improved healing of tendon graft ligament reconstructions. The device was validated for repeatability of the knee kinematic motion by measuring the force versus angular rotation response from repeated trials using cadaver rats.

A new paradigm for mechanobiological mechanisms in tumor metastasis.

Tumor metastases and epithelial to mesenchymal transition (EMT) involve tumor cell invasion and migration through the dense collagen-rich extracellular matrix surrounding the tumor. Little is neither known about the mechanobiological mechanisms involved in this process, nor the role of the mechanical forces generated by the cells in their effort to invade and migrate through the stroma. In this paper we propose a new fundamental mechanobiological mechanism involved in cancer growth and metastasis, which can be both protective or destructive depending on the magnitude of the forces generated by the cells.

Characterization of a macroporous polyvinyl alcohol scaffold for the repair of focal articular cartilage defects.

Focal cartilage defects reduce the ability of articular cartilage to resist mechanical loading and provide lubrication during joint motion. The limitations in current surgical treatments have motivated the use of biocompatible scaffolds as a future treatment option. Here we describe a second generation macroporous, polyvinyl alcohol (PVA) scaffold with independently tunable morphological and mechanical properties.

A novel macroporous polyvinyl alcohol scaffold promotes chondrocyte migration and interface formation in an in vitro cartilage defect model.

Scaffold-cartilage integration is critical for the clinical success of a scaffold used for the repair of a focal cartilage defect. In this study, a macroporous polyvinyl alcohol (PVA) scaffold was found to facilitate chondrocyte infiltration and interfacial matrix formation in a juvenile bovine in vitro cartilage defect model. These results were found to depend on the press-fit between the scaffold and the cartilage, pretreatment of the cartilage with collagenase prior to scaffold insertion, and chondrocyte preseeding of the scaffold.