Explainable deep learning and biomechanical modeling for TMJ disorder morphological risk factors.

Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis, development of targeted prevention, and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analyses of disease data sets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and mechanobiology. Our 3D convolutional neural network recognized TMJ disorder patients through participant-specific morphological features in condylar, ramus, and chin. Driven by deep learning model outputs, biomechanical modeling revealed that small mandibular size and flat condylar shape were associated with increased TMJ disorder risk through increased joint force, decreased tissue nutrient availability and cell ATP production, and increased TMJ disc strain energy density. Combining explainable deep learning and multiscale biomechanical modeling addresses the "mechanism unknown" limitation undermining translational confidence in clinical applications of deep learning and increases methodological accessibility for smaller clinical data sets by providing the crucial biomechanical context.

Viable Vitreous Grafts of Whole Porcine Menisci for Transplant in the Knee and Temporomandibular Joints.

The shortage of suitable donor meniscus grafts from the knee and temporomandibular joint (TMJ) impedes treatments for millions of patients. Vitrification offers a promising solution by transitioning these tissues into a vitreous state at cryogenic temperatures, protecting them from ice crystal damage using high concentrations of cryoprotectant agents (CPAs). However, vitrification's success is hindered for larger tissues (>3 mL) due to challenges in CPA penetration. Dense avascular meniscus tissues require extended CPA exposure for adequate penetration; however, prolonged exposure becomes cytotoxic. Balancing penetration and reducing cell toxicity is required. To overcome this hurdle, a simulation-based optimization approach is developed by combining computational modeling with microcomputed tomography (µCT) imaging to predict 3D CPA distributions within tissues over time accurately. This approach minimizes CPA exposure time, resulting in 85% viability in 4-mL meniscal specimens, 70% in 10-mL whole knee menisci, and 85% in 15-mL whole TMJ menisci (i.e., TMJ disc) post-vitrification, outperforming slow-freezing methods (20%-40%), in a pig model. The extracellular matrix (ECM) structure and biomechanical strength of vitreous tissues remain largely intact. Vitreous meniscus grafts demonstrate clinical-level viability (≥70%), closely resembling the material properties of native tissues, with long-term availability for transplantation. The enhanced vitrification technology opens new possibilities for other avascular grafts.

Nanowarming and ice-free cryopreservation of large sized, intact porcine articular cartilage.

Successful organ or tissue long-term preservation would revolutionize biomedicine. Cartilage cryopreservation enables prolonged shelf life of articular cartilage, posing the prospect to broaden the implementation of promising osteochondral allograft (OCA) transplantation for cartilage repair. However, cryopreserved large sized cartilage cannot be successfully warmed with the conventional convection warming approach due to its limited warming rate, blocking its clinical potential. Here, we develope a nanowarming and ice-free cryopreservation method for large sized, intact articular cartilage preservation. Our method achieves a heating rate of 76.8 °C min-1, over one order of magnitude higher than convection warming (4.8 °C min-1). Using systematic cell and tissue level tests, we demonstrate the superior performance of our method in preserving large cartilage. A depth-dependent preservation manner is also observed and recapitulated through magnetic resonance imaging and computational modeling. Finally, we show that the delivery of nanoparticles to the OCA bone side could be a feasible direction for further optimization of our method. This study pioneers the application of nanowarming and ice-free cryopreservation for large articular cartilage and provides valuable insights for future technique development, paving the way for clinical applications of cryopreserved cartilage.

Predicting post-total ankle arthroplasty walking speed based on preoperative gait mechanics.

Decreased walking speed is associated with impaired physical performance and function in older adults. Following total ankle arthroplasty (TAA), walking speed continues to be slower than age matched controls. The purpose of this study was to determine if patients 1 year post-TAA can achieve walking speed benchmarks and investigate if gait metrics are predictive of achieved benchmarks. 191 TAA patients were recruited and assessed pre-TAA and 1 year post-TAA. Kinetic and kinematic data were collected during seven self-selected speed barefoot walking trials along a 30-m walkway. Receiver operator curves were generated for each variable to determine threshold values needed to achieve walking speeds of 0.8, 0.9, 1.1, and 1.3 m/s. Each variable's predictive ability was classified according to the area under the curve. Ninety one percent of participants achieved a walking speed > 0.8 m/s, 85.3% achieved ≥0.9 m/s, 64.9% walked at ≥1.1 m/s, and 24.1% achieved a walking speed of 1.3 m/s by 1 year post-TAA. Walking speed pre-TAA was the strongest predictor with ankle moment, power and GRF data showing mixed results. Clinical Significance: 75.9% of participants were unable to walk at 1.3 m/s-a speed indicative of safely crossing a street. Variables predictive of postoperative walking speed benchmarks could be useful in developing interventions for the TAA population. The strongest predictor across all walking speed benchmarks was preoperative walking speed. A walking speed > 0.71 m/s was predictive of achieving 0.8 m/s 1 year post-TAA, while >1.09 m/s predicted 1.3 m/s 1 year post-TAA.

Racial differences in running and landing measures associated with injury risk vary by sex.

It is unknown whether running and landing mechanics differ between racial groups despite injury disparities between African Americans (AA) and white Americans (WA). This study aimed to identify potential racial differences in running and landing mechanics and understand whether anthropometric, strength, and health status factors contribute to these differences. Venous blood samples, anthropometry, lower-extremity strength, and health status assessments were collected (n = 84, 18-30y). Three-dimensional motion capture and force plate data were recorded during 7 running and 7 drop vertical jump trials. Racial effects were determined, and regression models evaluated explanatory factors. AA females ran with longer stance times (p = 0.003) than WA females, while AA males ran with smaller loading rates (p = 0.046) and larger peak vertical ground reaction forces (p = 0.036) than WA males. Frontal plane knee range of motion during landing was greater in AA females (p = 0.033) than WA females; larger waist circumference and weaker knee extension strength accounted for this significance. Although outcome measures were associated with physiologic, anthropometric, and activity measures, their explanatory power for race was ambiguous, except for knee range of motion in females. Modifiable factors explaining racial effects during landing in females are potential intervention targets to reduce racial health disparities in running and landing injuries.

Continuous similarity analysis in patient populations.

Decreased movement symmetry is associated with injury risk and accelerated disease progression. Methods to analyze continuous data either cannot be used in pathologic populations with abnormal movement patterns or are not defined in terms easily incorporated into clinical care. The purpose of this study was to develop a method of describing symmetry and movement quality in continuous time-series data that results in scores that can be readily incorporated into clinical care. Two scores were developed: (1) the symmetry score (SS) which evaluates similarities in time-series data between limbs and (2) the closeness-to-healthy score (CTHS) which evaluates the similarity of time-series data to a control population. Kinetic and kinematic data from 56 end-stage unilateral ankle arthritis (A-OA) patients and 56 healthy older adults, along with 16 anterior cruciate ligament reconstruction (ACLR) patients and 16 healthy young adults were used to test the ability for SS and CTHS to differentiate between healthy and patient groups. Unpaired t-tests, Cohen's D effect sizes, and receiver-operating-curve analyses assessed group differences [SPSS, V27, α = 0.05]. Patients had worse SS than controls and A-OA patients had worse CTHS compared to controls. SS had strong predictive capability, while the predictive capability of CTHS varied. Combined with clinically accessible data collection methods, the SS and CTHS could be used to evaluate patients' baseline movement quality, assess changes due to disease progression, and during recovery. Results could be utilized in clinical decision making to assess surgical intervention urgency and efficacy of surgical interventions or rehabilitation protocols to improve side-to-side limb symmetry.

Structure-function relationships of TMJ lateral capsule-ligament complex.

The human temporomandibular joint (TMJ) lateral capsule ligament (LCL) complex is debated as a fibrous capsule with distinct ligaments or ligamentous thickening, necessitating further evaluation of the complex and its role in TMJ anatomy and mechanics. This study explores the ultrastructural arrangement, biomechanical tensile properties, and biochemical composition of the human LCL complex including region-specific differences to explore the presence of a distinct temporomandibular ligament and sex-specific differences to inform evaluations of potential etiological mechanisms. LCL complex ultrastructural arrangement, biomechanical properties, and biochemical composition were determined using cadaveric samples. Statistical modeling assessed sex- and region-specific effects on LCL complex tissue properties. Collagen fiber coherency, collagen fiber bundle size, and elastin fiber count did not differ between sexes, but females trended higher in elastin fiber count. LCL complex water and sGAG content did not differ between sexes or regions, but collagen content was higher in the anterior region (311.0 ± 185.6 µg/mg) compared to the posterior region (221.0 ± 124.9 µg/mg) (p = 0.045) across sexes and in males (339.6 ± 170.6 µg/mg) compared to females (204.5 ± 130.7 µg/mg) (p = 0.006) across regions. Anterior failure stress (1.1 ± 0.7 MPa) was larger than posterior failure stress (0.6 ± 0.4 MPa) (p = 0.024). Regional differences confirm the presence of a mechanically and compositionally distinct temporomandibular ligament. Baseline sex-specific differences are critical for etiological investigations of sex disparities in TMJ disorders. These results have important biomechanical and clinical ramifications, providing critical baseline tissue material properties, informing the development of TMJ musculoskeletal models, and identifying new areas for etiologic investigations for temporomandibular disorders.

Effect of osteopathic manipulation on gait asymmetry.

CONTEXT: Movement and loading asymmetry are associated with an increased risk of musculoskeletal injury, disease progression, and suboptimal recovery. Osteopathic structural screening can be utilized to determine areas of somatic dysfunction that could contribute to movement and loading asymmetry. Osteopathic manipulation treatments (OMTs) targeting identified somatic dysfunctions can correct structural asymmetries and malalignment, restoring the ability for proper compensation of stresses throughout the body. Little is currently known about the ability for OMTs to reduce gait asymmetries, thereby reducing the risk of injury, accelerated disease progression, and suboptimal recovery. OBJECTIVES: To demonstrate whether osteopathic screening and treatment could alter movement and loading asymmetry during treadmill walking. METHODS: Forty-two healthy adults (20 males, 22 females) between the ages of 18 and 35 were recruited for this prospective intervention. Standardized osteopathic screening exams were completed by a single physician for each participant, and osteopathic manipulation was performed targeting somatic dysfunctions identified in the screening exam. Three-dimensional (3-D) biomechanical assessments, including the collection of motion capture and force plate data, were performed prior to and following osteopathic manipulation to quantify gait mechanics. Motion capture and loading data were processed utilizing Qualisys Track Manager and Visual 3D software, respectively. Asymmetry in the following temporal, kinetic, and kinematic measures was quantified utilizing a limb symmetry index (LSI): peak vertical ground reaction force, the impulse of the vertical ground reaction force, peak knee flexion angle, step length, stride length, and stance time. A 2-way repeated-measures analysis of variance model was utilized to evaluate the effects of time (pre/post manipulation) and sex (male/female) on each measure of gait asymmetry. RESULTS: Gait asymmetry in the peak vertical ground reaction force (-0.6%, p=0.025) and the impulse of the vertical ground reaction force (-0.3%, p=0.026) was reduced in males following osteopathic manipulation. There was no difference in gait asymmetry between time points in females. Osteopathic manipulation did not impact asymmetry in peak knee flexion angle, step length, stride length, or stance time. Among the participants, 59.5% (25) followed the common compensatory pattern, whereas 40.5% (17) followed the uncommon compensatory pattern. One third (33.3%, 14) of the participants showed decompensation at the occipitoatlantal (OA) junction, whereas 26.2% (11), one third (33.3%, 14), and 26.2% (11) showed decompensation at the cervicothoracic (CT), thoracolumbar (TL), and lumbosacral (LS) junctions, respectively. Somatic dysfunction at the sacrum, L5, right innominate, and left innominate occurred in 88.1% (37), 69.0% (29), 97.6% (41), and 97.6% (41) of the participants, respectively. CONCLUSIONS: Correcting somatic dysfunction can influence gait asymmetry in males; the sex-specificity of the observed effects of osteopathic manipulation on gait asymmetry is worthy of further investigation. Osteopathic structural examinations and treatment of somatic dysfunctions may improve gait symmetry even in asymptomatic individuals. These findings encourage larger-scale investigations on the use of OMT to optimize gait, prevent injury and the progression of disease, and aid in recovery after surgery.

Sexual dimorphisms in three-dimensional masticatory muscle attachment morphometry regulates temporomandibular joint mechanics.

Temporomandibular joint (TMJ) disorders disproportionally affect females, with female to male prevalence varying from 3:1 to 8:1. Sexual dimorphisms in masticatory muscle attachment morphometry and association with craniofacial size, critical for understanding sex-differences in TMJ function, have not been reported. The objective of this study was to determine sex-specific differences in three-dimensional (3D) TMJ muscle attachment morphometry and craniofacial sizes and their impact on TMJ mechanics. Human cadaveric TMJ muscle attachment morphometry and craniofacial anthropometry (10Males; 11Females) were determined by previously developed 3D digitization and imaging-based methods. Sex-differences in muscle attachment morphometry and craniofacial anthropometry, and their correlation were determined, respectively using multivariate general linear and linear regression statistical models. Subject-specific musculoskeletal models of the mandible were developed to determine effects of sexual dimorphisms in mandibular size and TMJ muscle attachment morphometry on joint loading during static biting. There were significant sex-differences in craniofacial size (p = 0.024) and TMJ muscle attachment morphometry (p < 0.001). TMJ muscle attachment morphometry was significantly correlated with craniofacial size. TMJ contact forces estimated from biomechanical models were significantly, 23% on average (p < 0.001), greater for females compared to those for males when generating the same bite forces. There were significant linear correlations between TMJ contact force and both 3D mandibular length (R2 = 0.48, p < 0.001) and muscle force moment arm ratio (R2 = 0.68, p < 0.001). Sexual dimorphisms in masticatory muscle morphology and craniofacial sizes play critical roles in subject-specific TMJ biomechanics. Sex-specific differences in the TMJ mechanical environment should be further investigated concerning mechanical fatigue of TMJ discs associated with TMJ disorders.

Racial differences in gait mechanics.

The effect of race has rarely been investigated in biomechanics studies despite racial health disparities in the incidence of musculoskeletal injuries and disease, hindering both treatment and assessment of rehabilitation. The purpose of this study was to test the hypothesis that racial differences in gait mechanics exist between African Americans (AA) and white Americans (WA). Ninety-two participants (18-30 years old) were recruited with equal numbers in each racial group and sex. Self-selected walking speed was measured for each participant. 3D motion capture and force plate data were recorded during 7 walking trials at regular and fast set speeds. Step length, step width, peak vertical ground reaction force, peak hip extension, peak knee flexion, and peak ankle plantarflexion were computed for all trials at both set speeds. Multivariate and post-hoc univariate ANOVA models were fit to determine main and interaction effects of sex and race (SPSS V26, α = 0.05). Self-selected walking speed was slower in AA (p = 0.004, ƞp2 = 0.088). No significant interactions between race and sex were identified. Males took longer steps (regular: p < 0.001, ƞp2 = 0.288, fast: p < 0.001, ƞp2 = 0.193) and had larger peak knee flexion (regular: p = 0.007, ƞp2 = 0.081, fast: p < 0.001, ƞp2 = 0.188) and ankle plantarflexion angles (regular: p = 0.050, ƞp2 = 0.044, fast: p = 0.049, ƞp2 = 0.044). Peak ankle plantarflexion angle (regular: p = 0.012, ƞp2 = 0.071, fast: p < 0.001, ƞp2 = 0.137) and peak hip extension angle during fast walking (p = 0.007, ƞp2 = 0.083) were smaller in AA. Equivalency in gait measures between racial groups should not be assumed. Racially diverse study samples should be prioritized in the development of future research and individualized treatment protocols.