Suzanne A. Maher

Dynamic Contact Mechanics of the Medial Meniscus as a Function of Radial Tear, Repair, and Partial Meniscectomy

BACKGROUND The menisci are integral to normal knee function. The purpose of this study was to measure the contact pressures transmitted to the medial tibial plateau under physiological loads as a function of the percentage of the meniscus involved by the radial tear or repair. Our hypotheses were that (1) there is a threshold size of radial tears above which contact mechanics are adversely affected, and (2) partial meniscectomy results in increased contact pressure compared with that found after meniscal repair. METHODS A knee simulator was used to apply physiological multidirectional dynamic gait loads across human cadaver knees. A sensor inserted below the medial meniscus recorded contact pressures in association with (1) an intact meniscus, (2) a radial tear involving 30% of the meniscal rim width, (3) a radial tear involving 60% of the width, (4) a radial tear involving 90% of the width, (5) an inside-out repair with horizontal mattress sutures, and (6) a partial meniscectomy. The effects of these different types of meniscal manipulation on the magnitude and location of the peak contact pressure were assessed at 14% and 45% of the gait cycle. RESULTS The peak tibial contact pressure in the intact knees was 6 +/- 0.5 MPa and 7.4 +/- 0.6 MPa at 14% and 45% of the gait cycle, respectively. The magnitude and location of the peak contact pressure were not affected by radial tears involving up to 60% of the meniscal rim width. Radial tears involving 90% resulted in a posterocentral shift in peak-pressure location manifested by an increase in pressure in that quadrant of 1.3 +/- 0.5 MPa at 14% of the gait cycle relative to the intact condition. Inside-out mattress suture repair of a 90% tear did not restore the location of the pressure peak to that of the intact knee. Partial meniscectomy led to a further increase in contact pressure in the posterocentral quadrant of 1.4 +/- 0.7 MPa at 14% of the gait cycle. CONCLUSIONS Large radial tears of the medial meniscus are not functionally equivalent to meniscectomies; the residual meniscus continues to provide some load transmission and distribution functions across the joint.

Image-Guided Tissue Engineering of Anatomically Shaped Implants via MRI and Micro-CT Using Injection Molding

This study demonstrates for the first time the development of engineered tissues based on anatomic geometries derived from widely used medical imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Computer-aided design and tissue injection molding techniques have demonstrated the ability to generate living implants of complex geometry. Due to its complex geometry, the meniscus of the knee was used as an example of this techniques capabilities. MRI and microcomputed tomography (microCT) were used to design custom-printed molds that enabled the generation of anatomically shaped constructs that retained shape throughout 8 weeks of culture. Engineered constructs showed progressive tissue formation indicated by increases in extracellular matrix content and mechanical properties. The paradigm of interfacing tissue injection molding technology can be applied to other medical imaging techniques that render 3D models of anatomy, demonstrating the potential to apply the current technique to engineering of many tissues and organs.

A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: Controlled release for cartilage tissue engineering

Because of similar mechanical properties to native cartilage, synthetic hydrogels based on poly(vinyl alcohol) (PVA) have been proposed for replacement of damaged articular cartilage, but they suffer from a complete lack of integration with surrounding tissue. In this study, insulin-like growth factor-1 (IGF-1), an important growth factor in cartilage regeneration, was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles embedded in the PVA hydrogels in a single step based on a double emulsion. The release of IGF-1 from these hydrogels was sustained over 6 weeks in vitro. Poly(glycolic acid) (PGA) fiber scaffolds were wrapped around the hydrogels, seeded with chondrocytes, and implanted subcutaneously in athymic mice. The release of IGF-1 enhanced cartilage formation in the layers surrounding the hydrogels, in terms of the content of extracellular matrix components and mechanical properties, and increased integration between the cartilage layers and the hydrogels, according to gross observation of the cross-sections and histology. The compressive modulus of the cartilage-hydrogel constructs without IGF-1 was 0.07±0.02MPa, compared to 0.17-0.2MPa for hydrogels that contained IGF-1. The biochemical and mechanical markers of cartilage formation were not different between the low and high concentrations of IGF-1, despite an order of magnitude difference in concentration. This study shows that the sustained release of IGF-1 can enhance tissue formation and points to a possible strategy for effecting integration with surrounding tissue.

Evaluation of a Porous Polyurethane Scaffold in a Partial Meniscal Defect Ovine Model

PURPOSE The objective of this study was to assess the performance of a degradable porous polyurethane scaffold in a partial meniscectomy ovine model. METHODS We subjected 42 skeletally mature ewes to unilateral partial excision of the lateral meniscus. In 19 animals the defect was left unfilled; in 23 animals a scaffold was inserted. Knees were examined by magnetic resonance imaging, gross inspection, and histologic inspection of the cartilage of the tibial plateau. RESULTS In contrast to what has been previously reported in a complete meniscal replacement model, cartilage damage did not occur under the site of scaffold implantation; this was likely influenced by the rapid infiltration of cells and the dense tissue that formed within the scaffold. Cartilage damage in both groups was located close to the midline of the joint. No significant difference in the condition of the articular cartilage of the tibial plateau was seen between groups up to 12 months postoperatively. This result was influenced by the fact that the partly meniscectomized knees also showed unexpected tissue regeneration within the defect site, which raises concern about the suitability of using a partial meniscectomy as a control in the ovine model. CONCLUSIONS Our study has shown that implantation of a polyurethane scaffold in a partial meniscectomy ovine model promotes tissue ingrowth without damaging the cartilage with which it articulates. CLINICAL RELEVANCE Meniscal deficiency is a common occurrence, the effective clinical management of which is limited by the absence of an off-the-shelf implantable construct.

Dynamic Contact Mechanics of Radial Tears of the Lateral Meniscus: Implications for Treatment

PURPOSE To characterize the effect of radial tears (RTs) of the lateral meniscus and their subsequent treatment (inside-out repair, partial meniscectomy) on joint contact mechanics during simulated gait. METHODS Six human cadaveric knees were mounted on a simulator programmed to mimic human gait. A sensor was inserted below the lateral meniscus to measure peak joint contact pressure location, magnitude, and contact area. The following conditions were compared: intact meniscus, 30% RT (at the popliteal hiatus), 60% RT, 90% RT, repair, and partial meniscectomy. Data were analyzed in the midstance phase of gait (14% and 45%) when axial force was at its highest (2,100 N). RESULTS Intact knees had peak contact pressures of 5.9 ± 0.9 MPa and 6.4 ± 1.1 MPa at 14% and 45% of gait, respectively. RTs of up to and including 60% had no effect on pressure magnitude or location. RTs of 90% resulted in significantly increased peak pressure (8.4 ± 1.1 MPa) in the postero-peripheral aspect of the tibial plateau and reduced contact area versus the intact knee, at 45% of gait. Repair resulted in a significant decrease in peak pressure (7.7 ± 1.0 MPa) relative to 90% RT but had no effect on contact area. Partial lateral meniscectomy resulted in areas and pressures that were not significantly different from 90% tears (8.7 ± 1.5 MPa). CONCLUSIONS Simulated large RTs of the lateral meniscus in the region of the popliteal hiatus show unfavorable dynamic contact mechanics that are not significantly different from those resulting from a partial lateral meniscectomy. Pressure was significantly reduced with inside-out repair but was not affected by partial meniscectomy; contact area was not restored to that of the intact condition for either procedure. CLINICAL RELEVANCE Large RTs in the region of the popliteal hiatus show unfavorable dynamic contact mechanics.

A new technique to measure the dynamic contact pressures on the Tibial Plateau

Studies of the load transfer role of the meniscus have been limited to static experimental and analytical approaches. The objective of this study was to develop an experimental technique to allow the contact pressures on the tibial plateau of cadaveric knees to be measured under dynamic physiological loads. Accordingly, we adapted a load-controlled knee joint simulator to accept a cadaveric sheep knee, programmed the simulator with sheep gait kinematics data, and utilized a pressure sensor array to measure the contact pressure distribution on the lateral tibial plateau during gait. The technique was applied to six sheep knees that were tested intact and after meniscectomy. Meniscectomy resulted in a 267% increase in average contact pressure, a 117% increase in peak contact pressure, and an 80% decrease in contact area, all measured at the point of maximum peak contact stress in the gait cycle. It is envisaged that the experimental model herein developed will allow for the screening of candidate materials prior to more expensive and time-consuming animal models.

A nanofibrous cell‐seeded hydrogel promotes integration in a cartilage gap model

The presence of a defect in mature articular cartilage can lead to degenerative changes of the joint. This is in part caused by the inability of cartilage to regenerate tissue that is capable of spanning a fissure or crack. In this study, we hypothesized that introduction of a biodegradable cell‐seeded nanofibrous hydrogel, Puramatrix™, into a cartilage gap would facilitate the generation of a mechanically stable interface. The effects of chondrocyte incorporation within the hydrogel and supplementation with transforming growth factor‐β3 (TGFβ3), a known regulator of cell growth and differentiation, on cartilage integration were examined mechanically and histologically as a function of cell density and incubation time. When supplemented with TGFβ3, the cell‐seeded hydrogel exhibited abundant matrix generation within the hydrogel and a corresponding increase in maximum push‐out stress as compared to all other groups. Furthermore, initial cell seeding density affected interfacial strength in a time‐dependent manner. This study suggests that a cell‐seeded TGFβ3‐supplemented hydrogel can encourage integration between two opposing pieces of articular cartilage. Copyright

Implantation of a synthetic meniscal scaffold improves joint contact mechanics in a partial meniscectomy cadaver model

Meniscal substitutes should ideally distribute loads across adjacent articular cartilage much in the way of the native tissue, thereby protecting the cartilage from degeneration. The objective of this study was to quantify the loads transferred to the tibial plateau after implantation of a porous polyurethane scaffold. Our hypothesis was that scaffold implantation would improve the contact mechanics of a partial meniscectomy knee. Six sheep cadaver knees were mounted in a load-controlled knee-joint simulator. A pressure-sensor sheet, secured to the tibial plateau, dynamically recorded pressure data over 10 gait cycles for the following conditions: (i) intact, (ii) partial meniscectomy, (iii) implanted scaffold, and (iv) total meniscectomy. Implantation of the scaffold increased the contact area and decreased the contact pressures compared to the meniscal defect knee. No significant difference was found between the average and peak contact pressures of the intact knees and scaffold-implanted knees; however, contact area was significantly lower for the scaffold-implanted knees compared to intact knees. Our hypothesis was accepted; replacement with a polyurethane scaffold improved knee-contact mechanics relative to a partially meniscectomized knee. On the basis of these findings, the scaffold will be evaluated for its chondroprotective capacity in an in vivo ovine model.

Dynamic contact stress patterns on the tibial plateaus during simulated gait: A novel application of normalized cross correlation

The spatial distribution and pattern of local contact stresses within the knee joint during activities of daily living have not been fully investigated. The objective of this study was to determine if common contact stress patterns exist on the tibial plateaus of human knees during simulated gait. To test this hypothesis, we developed a novel normalized cross-correlation (NCC) algorithm and applied it to the contact stresses on the tibial plateaus of 12 human cadaveric knees subjected to multi-directional loads mimicking gait. The contact stress profiles at different locations on the tibial plateaus were compared, where regions with similar contact stress patterns were identified across specimens. Three consistent regional patterns were found, among them two most prominent contact stress patterns were shared by 9-12 of all the knees and the third pattern was shared by 6-8 knees. The first pattern was located at the posterior aspect of the medial tibial plateau and had a single peak stress that occurred during the early stance phase. The second pattern was located at the central-posterior aspects of the lateral plateau and consisted of two peak stresses coincident with the timing of peak axial force at early and late stance. The third pattern was found on the anterior aspect of cartilage-to-cartilage contact region on the medial plateau consisted of double peak stresses. The differences in the location and profile of the contact stress patterns suggest that the medial and lateral menisci function to carry load at different points in the gait cycle: with the posterior aspect of the medial meniscus consistently distributing load only during the early phase of stance, and the posterior aspect of the lateral meniscus consistently distributing load during both the early and late phases of stance. This novel approach can help identify abnormalities in knee contact mechanics and provide a better understanding of the mechanical pathways leading to post-traumatic osteoarthritis.

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. The compressive moduli of the PVA scaffold increased with increasing polymer concentration and applied compressive strain, with values in the range for human articular cartilage (HA > 1000 kPa, EY > 500 kPa). Scaffolds also possessed strain‐dependent permeability and Poissons ratio. The interconnected macroporous network was found to facilitate chondrocyte seeding and proliferation through the scaffold over one week in culture. Overall, these promising characteristics demonstrate the potential of this macroporous scaffold for future studies in focal cartilage defect repair. Copyright