Keith D. Button

Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee

The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post-impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p<0.0001) compared to controls. Chronic meniscal damage was most prevalent in the medial central and medial posterior regions. Mechanical tests revealed an overall 19.4% increase in tibial plateau cartilage thickness (p=0.026), 34.8% increase in tibial plateau permeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p=0.036). In both meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post-injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee.

An optimized transversely isotropic, hyper-poro-viscoelastic finite element model of the meniscus to evaluate mechanical degradation following traumatic loading

Inverse finite element (FE) analysis is an effective method to predict material behavior, evaluate mechanical properties, and study differences in biological tissue function. The meniscus plays a key role in load distribution within the knee joint and meniscal degradation is commonly associated with the onset of osteoarthritis. In the current study, a novel transversely isotropic hyper-poro-viscoelastic constitutive formulation was incorporated in a FE model to evaluate changes in meniscal material properties following tibiofemoral joint impact. A non-linear optimization scheme was used to fit the model output to indentation relaxation experimental data. This study is the first to investigate rate of relaxation in healthy versus impacted menisci. Stiffness was found to be decreased (p=0.003), while the rate of tissue relaxation increased (p=0.010) at twelve weeks post impact. Total amount of relaxation, however, did not change in the impacted tissue (p=0.513).

Evaluation of Meniscal Mechanics and Proteoglycan Content in a Modified Anterior Cruciate Ligament Transection Model

Post-traumatic osteoarthritis (PTOA) develops as a result of traumatic loading that causes tears of the soft tissues in the knee. A modified transection model, where the anterior cruciate ligament (ACL) and both menisci were transected, was used on skeletally mature Flemish Giant rabbits. Gross morphological assessments, elastic moduli, and glycosaminoglycan (GAG) coverage of the menisci were determined to quantify the amount of tissue damage 12 weeks post injury. This study is one of the first to monitor meniscal changes after inducing combined meniscal and ACL transections. A decrease in elastic moduli as well as a decrease in GAG coverage was seen.

Assessment of cortical and trabecular bone changes in two models of post‐traumatic osteoarthritis

Subchondral bone is thought to play a significant role in the initiation and progression of the post‐traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed‐joint traumatic compressive impact model. Twelve weeks post‐injury bones were scanned via micro‐computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint‐wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans.

Specimen-Specific Computational Models of Ankle Sprains Produced in a Laboratory Setting

The use of computational modeling to predict injury mechanisms and severity has recently been investigated, but few models report failure level ligament strains. The hypothesis of the study was that models built off neutral ankle experimental studies would generate the highest ligament strain at failure in the anterior deltoid ligament, comprised of the anterior tibiotalar ligament (ATiTL) and tibionavicular ligament (TiNL). For models built off everted ankle experimental studies the highest strain at failure would be developed in the anterior tibiofibular ligament (ATiFL). An additional objective of the study was to show that in these computational models ligament strain would be lower when modeling a partial versus complete ligament rupture experiment. To simulate a prior cadaver study in which six pairs of cadaver ankles underwent external rotation until gross failure, six specimen-specific models were built based on computed tomography (CT) scans from each specimen. The models were initially positioned with 20 deg dorsiflexion and either everted 20 deg or maintained at neutral to simulate the cadaver experiments. Then each model underwent dynamic external rotation up to the maximum angle at failure in the experiments, at which point the peak strains in the ligaments were calculated. Neutral ankle models predicted the average of highest strain in the ATiTL (29.1 ± 5.3%), correlating with the medial ankle sprains in the neutral cadaver experiments. Everted ankle models predicted the average of highest strain in the ATiFL (31.2 ± 4.3%) correlating with the high ankle sprains documented in everted experiments. Strains predicted for ligaments that suffered gross injuries were significantly higher than the strains in ligaments suffering only a partial tear. The correlation between strain and ligament damage demonstrates the potential for modeling to provide important information for the study of injury mechanisms and for aiding in treatment procedure.

Rotational Stiffness of American Football Shoes Affects Ankle Biomechanics and Injury Severity

While previous studies have investigated the effect of shoe-surface interaction on injury risk, few studies have examined the effect of rotational stiffness of the shoe. The hypothesis of the current study was that ankles externally rotated to failure in shoes with low rotational stiffness would allow more talus eversion than those in shoes with a higher rotational stiffness, resulting in less severe injury. Twelve (six pairs) cadaver lower extremities were externally rotated to gross failure while positioned in 20 deg of pre-eversion and 20 deg of predorsiflexion by fixing the distal end of the foot, axially loading the proximal tibia, and internally rotating the tibia. One ankle in each pair was constrained by an American football shoe with a stiff upper, while the other was constrained by an American football shoe with a flexible upper. Experimental bone motions were input into specimen-specific computational models to examine levels of ligament elongation to help understand mechanisms of ankle joint failure. Ankles in flexible shoes allowed 6.7±2.4 deg of talus eversion during rotation, significantly greater than the 1.7±1.0 deg for ankles in stiff shoes (p = 0.01). The significantly greater eversion in flexible shoes was potentially due to a more natural response of the ankle during rotation, possibly affecting the injuries that were produced. All ankles failed by either medial ankle injury or syndesmotic injury, or a combination of both. Complex (more than one ligament or bone) injuries were noted in 4 of 6 ankles in stiff shoes and 1 of 6 ankles in flexible shoes. Ligament elongations from the computational model validated the experimental injury data. The current study suggested flexibility (or rotational stiffness) of the shoe may play an important role in both the severity of ankle injuries for athletes.

Efficacy of P188 on lapine meniscus preservation following blunt trauma

Traumatic injury to the knee leads to the development of post-traumatic osteoarthritis. The objective of this study was to characterize the effects of a single intra-articular injection of a non-ionic surfactant, Poloxamer 188 (P188), in preservation of meniscal tissue following trauma through maintenance of meniscal glycosaminoglycan (GAG) content and mechanical properties. Flemish Giant rabbits were subjected to a closed knee joint, traumatic compressive impact with the joint constrained to prevent anterior tibial translation. The contralateral limb served as an un-impacted control. Six animals (treated) received an injection of P188 in phosphate buffered saline (PBS) post trauma, and another six animals (sham) received a single injection of PBS to the impacted limb. Histological analyses for GAG was determined 6 weeks post trauma, and functional outcomes were assessed using stress relaxation micro-indentation. The impacted limbs of the sham group demonstrated a significant decrease in meniscal GAG coverage compared to non-impacted limbs (p<0.05). GAG coverage of the impacted P188 treated limbs was not significantly different than contralateral non-impacted limbs in all regions except the medial anterior (p<0.05). No significant changes were documented in mechanics for either the sham or treated groups compared to their respective control limbs. This suggests that a single intra-articular injection of P188 shows promise in prevention of trauma induced GAG loss.

The Acute Effect of Bipolar Radiofrequency Energy Thermal Chondroplasty on Intrinsic Biomechanical Properties and Thickness of Chondromalacic Human Articular Cartilage

Radio frequency energy (RFE) thermal chondroplasty has been a widely-utilized method of cartilage debridement in the past. Little is known regarding its effect on tissue mechanics. This study investigated the acute biomechanical effects of bipolar RFE treatment on human chondromalacic cartilage. Articular cartilage specimens were extracted (n = 50) from femoral condyle samples of patients undergoing total knee arthroplasty. Chondromalacia was graded with the Outerbridge classification system. Tissue thicknesses were measured using a needle punch test. Specimens underwent pretreatment load-relaxation testing using a spherical indenter. Bipolar RFE treatment was applied for 45 s and the indentation protocol was repeated. Structural properties were derived from the force-time data. Mechanical properties were derived using a fibril-reinforced biphasic cartilage model. Statistics were performed using repeated measures ANOVA. Cartilage thickness decreased after RFE treatment from a mean of 2.61 mm to 2.20 mm in Grade II, II-III, and III specimens (P < 0.001 each). Peak force increased after RFE treatment from a mean of 3.91 N to 4.91 N in Grade II and III specimens (P = 0.002 and P = 0.003, respectively). Equilibrium force increased after RFE treatment from a mean of 0.236 N to 0.457 N (P < 0.001 each grade). Time constant decreased after RFE treatment from a mean of 0.392 to 0.234 (P < 0.001 for each grade). Matrix modulus increased in all specimens following RFE treatment from a mean 259.12 kPa to 523.36 kPa (P < 0.001 each grade). Collagen fibril modulus decreased in Grade II and II-III specimens from 60.50 MPa to 42.04 MPa (P < 0.001 and P = 0.005, respectively). Tissue permeability decreased in Grade II and III specimens from 2.04 ∗10(-15) m(4)/Ns to 0.91 ∗10(-15) m(4)/Ns (P < 0.001 and P = 0.009, respectively). RFE treatment decreased thickness, time constant, fibril modulus, permeability, but increased peak force, equilibrium force, and matrix modulus. While resistance to shear and tension could be compromised due to removal of the superficial layer and decreased fibril modulus, RFE treatment increases matrix modulus and decreases tissue permeability which may restore the load- bearing capacity of the cartilage.

Comparison of two models of post‐traumatic osteoarthritis; Temporal degradation of articular cartilage and menisci

The objective of this study was to compare longitudinal results from two models of combined anterior cruciate ligament (ACL) and meniscal injury. A modified ACL transection (mACLT) model and a traumatic impact (ACLF) model were used to create an ACL rupture and acute meniscal damage in a Flemish Giant animal model. The animals were euthanized at time points of 4, 8, or 12 weeks. The menisci were assessed for equilibrium and instantaneous compressive modulus, as well as glycosaminoglycan (GAG) coverage. The articular cartilage was mechanically assessed for thickness, matrix modulus, fiber modulus, and permeability. Articular cartilage GAG coverage, fissuring, tidemark integrity, and subchondral bone thickness were measured. Both models resulted in damage indicative of osteoarthritis, including decreased meniscal mechanics and GAG coverage, increased permeability and fissuring of articular cartilage, and decreased GAG coverage. The mACLT model had an early and lasting effect on the menisci mechanics and GAG coverage, while cartilage damage was not significantly affected until 12 weeks. The ACLF model resulted in an earlier change of articular cartilage GAG coverage and fissuring in both the 8 and 12 week groups. The menisci were only significantly affected at the 12 week time point in the ACLF model. We concluded the progression of post traumatic osteoarthritis was dependent on injury modality: a point to be considered in future investigations.

A study of acute and chronic tissue changes in surgical and traumatically-induced experimental models of knee joint injury using magnetic resonance imaging and micro-computed tomography

OBJECTIVE The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. METHODS A 3-T clinical magnet and micro-computed tomography (μCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). RESULTS All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. CONCLUSIONS The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time.