Synthetic PVA Osteochondral Implants for the Knee Joint: Mechanical Characteristics During Simulated Gait.

BACKGROUND: Although polyvinyl alcohol (PVA) implants have been developed and used for the treatment of femoral osteochondral defects, their effect on joint contact mechanics during gait has not been assessed. PURPOSE/HYPOTHESIS: The purpose was to quantify the contact mechanics during simulated gait of focal osteochondral femoral defects and synthetic PVA implants (10% and 20% by volume of PVA), with and without porous titanium (pTi) bases. It was hypothesized that PVA implants with a higher polymer content (and thus a higher modulus) combined with a pTi base would significantly improve defect-related knee joint contact mechanics. STUDY DESIGN: Controlled laboratory study. METHODS: Four cylindrical implants were manufactured: 10% PVA, 20% PVA, and 10% and 20% PVA disks mounted on a pTi base. Devices were implanted into 8 mm-diameter osteochondral defects created on the medial femoral condyles of 7 human cadaveric knees. Knees underwent simulated gait and contact stresses across the tibial plateau were recorded. Contact area, peak contact stress, the sum of stress in 3 regions of interest across the tibial plateau, and the distribution of stresses, as quantified by tracking the weighted center of contact stress throughout gait, were computed for all conditions. RESULTS: An osteochondral defect caused a redistribution of contact stress across the plateau during simulated gait. Solid PVA implants did not improve contact mechanics, while the addition of a porous metal base led to significantly improved joint contact mechanics. Implants consisting of a 20% PVA disk mounted on a pTi base significantly improved the majority of contact mechanics parameters relative to the empty defect condition. CONCLUSION: The information obtained using our cadaveric test system demonstrated the mechanical consequences of femoral focal osteochondral defects and provides biomechanical support to further pursue the efficacy of high-polymer-content PVA disks attached to a pTi base to improve contact mechanics. CLINICAL RELEVANCE: As a range of solutions are explored for the treatment of osteochondral defects, our preclinical cadaveric testing model provides unique biomechanical evidence for the continued investigation of novel solutions for osteochondral defects.

Lateral Meniscal Graft Transplantation: Effect of Fixation Method on Joint Contact Mechanics During Simulated Gait.

BACKGROUND: Controversy exists regarding the optimal bony fixation technique for lateral meniscal allografts. PURPOSE/HYPOTHESIS: The objective was to quantify knee joint contact mechanics across the lateral plateau for keyhole and bone plug meniscal allograft transplant fixation techniques throughout simulated gait. It was hypothesized that both methods of fixation would improve contact mechanics relative to the meniscectomized condition, while keyhole fixation would restore the distribution of contact stress closer to that of the intact knee. STUDY DESIGN: Controlled laboratory study. METHODS: Six human cadaveric knees were mounted on a multidirectional dynamic simulator and subjected to the following conditions: (1) native intact meniscus, (2) keyhole fixation of the native meniscus, (3) bone plug fixation of the native meniscus, and (4) meniscectomy. Contact area, peak contact stress, and the distribution of stress across the tibial plateau were computed at 14% and 45% of the gait cycle, at which axial forces are at their highest. Translation of the weighted center of contact stress throughout simulated gait was computed. RESULTS: Both bony fixation techniques improved contact mechanics relative to the meniscectomized condition. The keyhole technique was not significantly different from the intact condition for the following metrics: contact area, peak contact stress, distribution of force between the meniscal footprint and cartilage-to-cartilage contact, and the position of the weighted center of contact. In contrast, bone plug fixation resulted in a significant decrease of 21% to 28% in contact area at 14% and 45% of the simulated gait cycle, a significant increase in peak contact stresses of 34% at 45% of the gait cycle, and a shift in the weighted center of contact, which increased forces in the cartilage-to-cartilage contact area at 45% of the gait cycle. CONCLUSION: While both keyhole and bone plug fixation methods improved lateral compartment contact mechanics relative to the meniscectomized knee, keyhole fixation restored contact mechanics closer to that of the intact knee. CLINICAL RELEVANCE: Method of meniscal fixation is under the direct control of the surgeon. From a biomechanics perspective, keyhole fixation is advocated for its ability to mimic intact knee joint contact mechanics.

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. We hypothesized that the magnitude of the mechanical discontinuity at the scaffold-cartilage interface would be related to decreased integration. To test this hypothesis, chondrocyte seeded scaffolds were embedded into cartilage explants, pre-cultured for 14 days, and then mechanically loaded for 28 days at either 1N or 6N of applied load. Constructs were kept either peripherally confined or unconfined throughout the duration of the experiment. Stress, strain, fluid flow, and relative displacements at the cartilage-scaffold interface and within the scaffold were quantified using biphasic, inhomogeneous finite element models (bFEMs). The bFEMs indicated compressive and shear stress discontinuities occurred at the scaffold-cartilage interface for the confined and unconfined groups. The mechanical strength of the scaffold-cartilage interface and scaffold GAG content were higher in the radially confined 1N loaded groups. Multivariate regression analyses identified the strength of the interface prior to the commencement of loading and fluid flow within the scaffold as the main factors associated with scaffold-cartilage integration. Our study suggests a minimum level of scaffold-cartilage integration is needed prior to the commencement of loading, although the exact threshold has yet to be identified. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self-crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5 to 16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press-fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage.

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant.

BACKGROUND: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. METHODS: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 µg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. RESULTS: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged. CONCLUSIONS: iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface. CLINICAL RELEVANCE: Our murine model is an excellent platform on which to study biological enhancement of cancellous osseointegration.

A statistically-augmented computational platform for evaluating meniscal function.

Meniscal implants have been developed in an attempt to provide pain relief and prevent pathological degeneration of articular cartilage. However, as yet there has been no systematic and comprehensive analysis of the effects of the meniscal design variables on meniscal function across a wide patient population, and there are no clear design criteria to ensure the functional performance of candidate meniscal implants. Our aim was to develop a statistically-augmented, experimentally-validated, computational platform to assess the effect of meniscal properties and patient variables on knee joint contact mechanics during the activity of walking. Our analysis used Finite Element Models (FEMs) that represented the geometry, kinematics as based on simulated gait and contact mechanics of three laboratory tested human cadaveric knees. The FEMs were subsequently programmed to represent prescribed meniscal variables (circumferential and radial/axial moduli-Ecm, Erm, stiffness of the meniscal attachments-Slpma, Slamp) and patient variables (varus/valgus alignment-VVA, and articular cartilage modulus-Ec). The contact mechanics data generated from the FEM runs were used as training data to a statistical interpolator which estimated joint contact data for untested configurations of input variables. Our data suggested that while Ecm and Erm of a meniscus are critical in determining knee joint mechanics in early and late stance (peak 1 and peak 3 of the gait cycle), for some knees that have greater laxity in the mid-stance phase of gait, the stiffness of the articular cartilage, Ec, can influence force distribution across the tibial plateau. We found that the medial meniscus plays a dominant load-carrying role in the early stance phase and less so in late stance, while the lateral meniscus distributes load throughout gait. Joint contact mechanics in the medial compartment are more sensitive to Ecm than those in the lateral compartment. Finally, throughout stance, varus-valgus alignment can overwhelm these relationships while the stiffness of meniscal attachments in the range studied have minimal effects on the knee joint mechanics. In summary, our statistically-augmented, computational platform allowed us to study how meniscal implant design variables (which can be controlled at the time of manufacture or implantation) interact with patient variables (which can be set in FEMs but cannot be controlled in patient studies) to affect joint contact mechanics during the activity of simulated walking.