The evaluation of a multiphasic 3D-bioplotted scaffold seeded with adipose derived stem cells to repair osteochondral defects in a porcine model.

There is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D-bioplotted osteochondral scaffold design that can drive site-specific tissue formation when seeded with adipose-derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and compared to both open lesions and autologous explants. ICRS II evaluation indicated that defects with ASC-seeded scaffolds had healing that most closely resembled the aulogous explant. Scaffold-facilitated subchondral bone repair mimicked the structure of native bone tissue, but cartilage matrix staining was not apparent within the scaffold. The open lesions had the highest volumetric infill detected using CT analysis (p < 0.05), but the repair tissue was largely disorganized. The acellular scaffold without a tidemark had significantly more volumetric filling than either the acellular or ASC seeded groups containing a tidemark (p < 0.05), suggesting that the tidemark limited cell infiltration into the cartilage portion of the scaffold. Overall, scaffold groups repaired the defect more successfully than an open lesion but achieved limited repair in the cartilage region. With further optimization, this approach holds potential to treat focal cartilage lesions in a highly personalized manner using a human patient's own ASC cells.

Using TENS to Enhance Therapeutic Exercise in Individuals with Knee Osteoarthritis.

Transcutaneous electrical nerve stimulation (TENS) facilitates quadriceps voluntary activation in experimental settings. Augmenting therapeutic exercise (TE) with TENS may enhance the benefits of TE in individuals with knee osteoarthritis (KOA) and quadriceps voluntary activation failure (QVAF). PURPOSE: This study aimed to determine the effect of TENS + TE on patient-reported function, quadriceps strength, and voluntary activation, as well as physical performance compared with sham TENS + TE (Sham) and TE alone in individuals with symptomatic KOA and QVAF. METHODS: Ninety individuals participated in a double-blinded randomized controlled trial. Everyone received 10 standardized TE sessions of physical therapy. TENS + TE and Sham groups applied the respective devices during all TE sessions and throughout activities of daily living over 4 wk. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC), quadriceps strength, and voluntary activation, as well as a 20-m walk test, chair-stand test, and stair-climb test were performed at baseline, after the 4-wk intervention (post 1) and at 8 wk after the start of the intervention (post 2). Mixed-effects models were used to determine between-group differences between baseline and post 1, as well as baseline and post 2. RESULTS: Improvements in WOMAC subscales, quadriceps strength, and voluntary activation, 20-m walk times, chair-stand repetitions, and stair-climb time were found at post 1 and post 2 compared with baseline for all groups (P < 0.05). WOMAC Pain and Stiffness improved in the TENS + TE group compared with TE alone at post 1 (P < 0.05); yet, no other between-group differences were found. CONCLUSIONS: TE effectively improved patient-reported function, quadriceps strength, and voluntary activation, as well as physical performance in individuals with symptomatic KOA and QVAF, but augmenting TE with TENS did not improve the benefits of TE.

Medial Unloader Braces and Lateral Heel Wedges Do not Alter Gait Biomechanics in Healthy Young Adults.

Context: Orthotic devices such as medial unloader knee braces and lateral heel wedges may limit cartilage loading following trauma or surgical repair. However, little is known regarding their effects on gait biomechanics in young, healthy individuals who are at risk of cartilage injury during physical activity due to greater athletic exposure compared with older adults. Objective: Determine the effect of medial unloader braces and lateral heel wedges on lower-extremity kinematics and kinetics in healthy, young adults. Design: Cross-sectional crossover design. Setting: Laboratory setting. Patients: Healthy, young adults who were recreationally active (30 min/d for 3 d/wk) between 18 and 35 years of age, who were free from orthopedic injury for at least 6 months, and with no history of lower-extremity orthopedic surgery. Interventions: All subjects completed normal over ground walking with a medial unloader brace at 2 different tension settings and a lateral heel wedge for a total of 4 separate walking conditions. Main Outcome Measures: Frontal plane knee angle at heel strike, peak varus angle, peak internal knee valgus moment, and frontal plane angular impulse were compared across conditions. Results: The medial unloader brace at 50% (-2.04° [3.53°]) and 100% (-1.80° [3.63°]) maximum load placed the knee in a significantly more valgus orientation at heel strike compared with the lateral heel wedge condition (-0.05° [2.85°]). However, this difference has minimal clinical relevance. Neither of the orthotic devices altered knee kinematics or kinetics relative to the control condition. Conclusions: Although effective in older adults and individuals with varus knee alignment, medial unloader braces and lateral heel wedges do not influence gait biomechanics in young, healthy individuals.

Walking Ground Reaction Force Post-ACL Reconstruction: Analysis of Time and Symptoms.

PURPOSE: The association between lower-extremity loading and clinically relevant knee symptoms at different time points after anterior cruciate ligament reconstruction (ACLR) is unclear. Vertical ground reaction force (vGRF) from walking was compared between individuals with and without clinically relevant knee symptoms in three cohorts: <12 months post-ACLR, 12-24 months post-ACLR, and >24 months post-ACLR. METHODS: One hundred twenty-eight individuals with unilateral ACLR were classified as symptomatic or asymptomatic, based on previously defined cutoff values for the Knee Osteoarthritis and Injury Outcome Score (<12 months post-ACLR [symptomatic n = 28, asymptomatic n = 24]; 12-24 months post-ACLR [symptomatic n = 15, asymptomatic n = 15], and >24 months post-ACLR [symptomatic, n = 13; asymptomatic, n = 33]). Vertical ground reaction force exerted on the ACLR limb was collected during walking gait, and functional analyses of variance were used to evaluate the effects of symptoms and time post-ACLR on vGRF throughout stance phase (α = 0.05). RESULTS: Symptomatic individuals, <12 months post-ACLR, demonstrated less vGRF during both vGRF peaks (i.e., weight acceptance and propulsion) and greater vGRF during midstance, compared to asymptomatic individuals. Vertical ground reaction force characteristics were not different between symptomatic and asymptomatic individuals for most of stance in individuals between 12 and 24 months post-ACLR. Symptomatic individuals who were >24 months post-ACLR, exhibited greater vGRF during both peaks, but lesser vGRF during midstance, compared to asymptomatic individuals. CONCLUSION: Relative to asymptomatic individuals, symptomatic individuals are more likely to underload the ACLR limb early after ACLR (i.e., <12 months) during both vGRF peaks, but overload the ACLR limb, during both vGRF peaks, at later time points (i.e., >24 months). We propose these differences in lower-extremity loading during walking might have implications for long-term knee health, and should be considered when designing therapeutic interventions for individuals with an ACLR.

Gait biomechanics in individuals with patellar tendon and hamstring tendon anterior cruciate ligament reconstruction grafts.

Anterior cruciate ligament reconstruction (ACLR) restores joint stability following ACL injury but does not attenuate the heightened risk of developing knee osteoarthritis. Additionally, patellar tendon (PT) grafts incur a greater risk of osteoarthritis compared to hamstring grafts (HT). Aberrant gait biomechanics, including greater loading rates (i.e. impulsive loading), are linked to the development of knee osteoarthritis. However, the role of graft selection on walking gait biomechanics linked to osteoarthritis is poorly understood, thus the purpose of this study was to compare walking gait biomechanics between individuals with HT and PT grafts. Ninety-eight (74 PT; 24 HT) subjects with a history of ACLR performed walking gait at a self-selected speed from which the peak vertical ground reaction force (vGRF) during the first 50% of the stance phase and its instantaneous loading rate, peak internal knee extension and valgus moments, and peak knee flexion and varus angles were obtained. When controlling for time since ACLR and quadriceps strength, there were no differences in any kinetic or kinematic variables between graft types. While not significant, 44% of the PT cohort were identified as impulsive loaders (displaying a heelstrike transient in the majority of walking trials) compared to only 25% of the HT cohort (odds ratio = 2.3). This more frequent observation of impulsive loading may contribute to the greater risk of osteoarthritis with PT grafts. Future research is necessary to determine if impulsive loading and small magnitude differences between graft types contribute to osteoarthritis risk when extrapolated over thousands of steps per day.

Walking gait asymmetries 6 months following anterior cruciate ligament reconstruction predict 12-month patient-reported outcomes.

The study sought to determine the association between gait biomechanics (vertical ground reaction force [vGRF], vGRF loading rate [vGRF-LR]) collected 6 months following anterior cruciate ligament reconstruction (ACLR) with patient-reported outcomes at 12 months following ACLR. Walking gait biomechanics and all subsections of the Knee Injury and Osteoarthritis Outcomes Score (KOOS) were collected at 6 and 12 months following ACLR, respectively, in 25 individuals with a unilateral ACLR. Peak vGRF and peak instantaneous vGRF-LR were extracted from the first 50% of the stance phase. Limb symmetry indices (LSI) were used to normalize outcomes in the ACLR limb to that of the uninjured limb (ACLR/uninjured). Linear regression analyses were used to determine associations between biomechanical outcomes and KOOS while accounting for walking speed. Receiver operator characteristic curves were used to determine the accuracy of 6-month biomechanical outcomes for identifying individuals with acceptable patient-reported outcomes, using previously defined KOOS cut-off scores, 12 months post-ACLR. Individuals with lower peak vGRF LSI 6 months post-ACLR demonstrated worse patient-reported outcomes (KOOS Pain, Activities of Daily life, Sport and Recreation, Quality of Life) at the 12-month exam. A peak vGRF LSI ≥0.99 6 months following ACLR associated with 13.33× higher odds of reporting acceptable patient-reported outcomes 12 months post-ACLR. Lesser peak vGRF LSI during walking at 6-months post-ACLR may be a critical indicator of worse future patient-reported outcomes. Clinical significance achieving early symmetrical lower extremity loading and minimizing under-loading of the ACLR limb during walking may be a potential therapeutic target for improving patient-reported outcomes post-ACLR. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2932-2940, 2018.

Quadriceps Rate of Torque Development and Disability in Persons With Tibiofemoral Osteoarthritis.

Background Declines in the ability to rapidly generate quadriceps muscle torque may underlie disability in individuals with tibiofemoral osteoarthritis. Objective To determine whether quadriceps rate of torque development (RTD) predicts self-reported disability and physical performance outcomes in individuals with tibiofemoral osteoarthritis. Methods This controlled laboratory, cross-sectional study assessed quadriceps strength and RTD in 76 individuals (55% female; mean ± SD age, 61.83 ± 7.11 years) with symptomatic and radiographic tibiofemoral osteoarthritis. Early (0-50 milliseconds), late (100-200 milliseconds), and overall peak RTDs were quantified in the symptomatic (involved) and contralateral limbs and used to calculate bilateral average values. Disability was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale and 3 physical performance tests, including the (1) 20-m fast-paced walk, (2) 30-second chair stand, and (3) timed stair climb. Separate univariate regression models were used to determine the unique associations among measures of quadriceps RTD, WOMAC function score, and physical performance outcomes after accounting for quadriceps strength (change in R2). Results Greater involved-side late RTD and greater bilateral average early RTD were associated with faster walking (change in R2 = 0.05, P = .013 and change in R2 = 0.05, P = .043, respectively). Greater bilateral average late RTD was associated with faster walking (change in R2 = 0.20, P<.001) and faster stair climb (change in R2 = 0.11, P = .001). No quadriceps RTD variable was significantly associated with WOMAC function score (change in R2 range, <0.01-0.017). Conclusion Involved-limb quadriceps RTD was weakly associated with physical performance outcomes, but not self-reported disability, in individuals with tibiofemoral osteoarthritis. Bilateral average quadriceps RTD was moderately associated with walking speed. Level of Evidence Prognosis, level 2b. J Orthop Sports Phys Ther 2018;48(9):694-703. Epub 22 May 2018. doi:10.2519/jospt.2018.7898.

Time between anterior cruciate ligament injury and reconstruction and cartilage metabolism six-months following reconstruction.

BACKGROUND: To determine the association between time from injury to ACL reconstruction (TimeInjury-ACLR) and biochemical markers of cartilage metabolism and inflammation six months following ACL reconstruction (ACLR). METHODS: Individuals with a unilateral ACL injury were enrolled at initial presentation in the orthopedic clinic; blood was collected six months following ACLR. Enzyme-linked immunosorbent assays were used to analyze the ratio of serum concentrations of type-II collagen breakdown (C2C) to synthesis (CPII), plasma matrix metalloproteinase-3 (MMP-3), interleukin-6 (IL-6), and serum aggrecan neoepitope (ARGS). We used separate linear regressions to assess associations between biochemical markers and TimeInjury-ACLR. RESULTS: Twenty-two participants (50% females, mean [SD], age 21.9 [4.5] years old; BMI 23.8 [2.6] kg/m2) completed the study. TimeInjury-ACLR ranged from nine to 67days (31.0 [14.4days]). Greater TimeInjury-ACLR predicted greater serum C2C:CPII ratios six months following ACLR (C2C:CPII=0.15 [0.02], R2=0.213, P=0.030). Males (R2=0.733, P=0.001) but not females (R2=0.030, P=0.609) demonstrated a significant association between greater C2C:CPII and TimeInjury-ACLR at the six-month follow-up exam. TimeInjury-ACLR did not associate with IL-6, MMP-3, or ARGS at six months. CONCLUSIONS: Greater time between injury and ACL reconstruction was associated with greater serum C2C:CPII six months following ACLR in males but not females, and IL-6, MMP-3, and ARGS levels were not associated with TimeInjury-ACLR in males or females. The time between ACL injury and ACLR may affect collagen metabolism in males and should be further investigated in a larger study along with other patient-relevant outcomes.

Biochemical markers of cartilage metabolism are associated with walking biomechanics 6-months following anterior cruciate ligament reconstruction.

The purpose of our study was to determine the association between biomechanical outcomes of walking gait (peak vertical ground reaction force [vGRF], vGRF loading rate [vGRF-LR], and knee adduction moment [KAM]) 6 months following anterior cruciate ligament reconstruction (ACLR) and biochemical markers of serum type-II collagen turnover (collagen type-II cleavage product to collagen type-II C-propeptide [C2C:CPII]), plasma degenerative enzymes (matrix metalloproteinase-3 [MMP-3]), and a pro-inflammatory cytokine (interleukin-6 [IL-6]). Biochemical markers were evaluated within the first 2 weeks (6.5 ± 3.8 days) following ACL injury and again 6 months following ACLR in eighteen participants. All peak biomechanical outcomes were extracted from the first 50% of the stance phase of walking gait during a 6-month follow-up exam. Limb symmetry indices (LSI) were used to normalize the biomechanical outcomes in the ACLR limb to that of the contralateral limb (ACLR/contralateral). Bivariate correlations were used to assess associations between biomechanical and biochemical outcomes. Greater plasma MMP-3 concentrations after ACL injury and at the 6-month follow-up exam were associated with lesser KAM LSI. Lesser KAM was associated with greater plasma IL-6 at the 6-month follow-up exam. Similarly, lesser vGRF-LR LSI was associated with greater plasma MMP-3 concentrations at the 6-month follow-up exam. Lesser peak vGRF LSI was associated with higher C2C:CPII after ACL injury, yet this association was not significant after accounting for walking speed. Therefore, lesser biomechanical loading in the ACLR limb, compared to the contralateral limb, 6 months following ACLR may be related to deleterious joint tissue metabolism that could influence future cartilage breakdown. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2288-2297, 2017.

Greater intracortical inhibition associates with lower quadriceps voluntary activation in individuals with ACL reconstruction.

Decreased voluntary activation contributes to quadriceps weakness following anterior cruciate ligament reconstruction (ACLR). Alterations in neural excitability are likely responsible for reductions in quadriceps voluntary activation, and may be due to specific alterations in intracortical inhibition and facilitation. Therefore, we sought to determine if intracortical inhibition (SICI) and intracortical facilitation (ICF) associate with quadriceps voluntary activation in individuals with ACLR. Twenty-seven participants with a primary, unilateral ACLR were enrolled in this study. Bilateral central activation ratio (CAR) and paired-pulse transcranial magnetic stimulation were used to assess quadriceps voluntary activation, as well as SICI and ICF in the vastus medalis, respectively. Pearson Product Moment correlations were used to determine the association between CAR and (1) SICI, and (2) ICF in each limb. Lesser CAR associated with lesser SICI amplitude (r = 0.502, P = 0.008) in the ACLR limb. No associations in the contralateral limb were significant. Our results suggest greater intracortical inhibition associates with lesser voluntary activation in individuals with ACL. Implementing interventions that target intracortical inhibition may aid in restoring quadriceps voluntary activation following ACLR.