Juan C. Villa-Camacho

Biomechanics and Mechanobiology of Trabecular Bone: A Review

Trabecular bone is a highly porous, heterogeneous, and anisotropic material which can be found at the epiphyses of long bones and in the vertebral bodies. Studying the mechanical properties of trabecular bone is important, since trabecular bone is the main load bearing bone in vertebral bodies and also transfers the load from joints to the compact bone of the cortex of long bones. This review article highlights the high dependency of the mechanical properties of trabecular bone on species, age, anatomic site, loading direction, and size of the sample under consideration. In recent years, high resolution micro finite element methods have been extensively used to specifically address the mechanical properties of the trabecular bone and provide unique tools to interpret and model the mechanical testing experiments. The aims of the current work are to first review the mechanobiology of trabecular bone and then present classical and new approaches for modeling and analyzing the trabecular bone microstructure and macrostructure and corresponding mechanical properties such as elastic properties and strength.

On-Demand Dissolution of a Dendritic Hydrogel-based Dressing for Second-Degree Burn Wounds through Thiol-Thioester Exchange Reaction.

An adhesive yet easily removable burn wound dressing represents a breakthrough in second-degree burn wound care. Current second-degree burn wound dressings absorb wound exudate, reduce bacterial infections, and maintain a moist environment for healing, but are surgically or mechanically debrided from the wound, causing additional trauma to the newly formed tissues. We have developed an on-demand dissolvable dendritic thioester hydrogel burn dressing for second-degree burn care. The hydrogel is composed of a lysine-based dendron and a PEG-based crosslinker, which are synthesized in high yields. The hydrogel burn dressing covers the wound and acts as a barrier to bacterial infection in an in vivo second-degree burn wound model. A unique feature of the hydrogel is its capability to be dissolved on-demand, via a thiol-thioester exchange reaction, allowing for a facile burn dressing removal.

Does CT-based Rigidity Analysis Influence Clinical Decision-making in Simulations of Metastatic Bone Disease?

BackgroundThere is a need to improve the prediction of fracture risk for patients with metastatic bone disease. CT-based rigidity analysis (CTRA) is a sensitive and specific method, yet its influence on clinical decision-making has never been quantified.Questions/purposesWhat is the influence of CTRA on providers’ perceived risk of fracture? (2) What is the influence of CTRA on providers’ treatment recommendations in simulated clinical scenarios of metastatic bone disease of the femur? (3) Does CTRA improve interobserver agreement regarding treatment recommendations?MethodsWe conducted a survey among 80 academic physicians (orthopaedic oncologists, musculoskeletal radiologists, and radiation oncologists) using simulated vignettes of femoral lesions presented as three separate scenarios: (1) no CTRA input (baseline); (2) CTRA input suggesting increased risk of fracture (CTRA+); and (3) CTRA input suggesting decreased risk of fracture (CTRA−). Participants were asked to rate the patient’s risk of fracture on a scale of 0% to 100% and to provide a treatment recommendation. Overall response rate was 62.5% (50 of 80).ResultsWhen CTRA suggested an increased risk of fracture, physicians perceived the fracture risk to be slightly greater (37% ± 3% versus 42% ± 3%, p < 0.001; mean difference [95% confidence interval {CI}] = 5% [4.7%–5.2%]) and were more prone to recommend surgical stabilization (46% ± 9% versus 54% ± 9%, p < 0.001; mean difference [95% CI] = 9% [7.9–10.1]). When CTRA suggested a decreased risk of fracture, physicians perceived the risk to be slightly decreased (37% ± 25% versus 35% ± 25%, p = 0.04; mean difference [95% CI] = 2% [2.74%–2.26%]) and were less prone to recommend surgical stabilization (46% ± 9% versus 42% ± 9%, p < 0.03; mean difference [95% CI] = 4% [3.9–5.1]). The effect size of the influence of CTRA on physicians’ perception of fracture risk and treatment planning varied with lesion severity and specialty of the responders. CTRA did not increase interobserver agreement regarding treatment recommendations when compared with the baseline scenario (κ = 0.41 versus κ = 0.43, respectively).ConclusionsBased on this survey study, CTRA had a small influence on perceived fracture risk and treatment recommendations and did not increase interobserver agreement. Further work is required to properly introduce this technique to physicians involved in the care of patients with metastatic lesions. Given the number of preclinical and clinical studies outlining the efficacy of this technique, better education through presentations at seminars/webinars and symposia will be the first step. This should be followed by clinical trials to establish CTRA-based clinical guidelines based on evidence-based medicine. Increased exposure of clinicians to CTRA, including its underlying methodology to study bone structural characteristics, may establish CTRA as a uniform guideline to assess fracture risk.Level of EvidenceLevel III, economic and decision analyses.

A hydrogel sealant for the treatment of severe hepatic and aortic trauma with a dissolution feature for post-emergent care

Non-compressible hemorrhage is an important cause of pre-hospital death following trauma, and immediate control of blood loss is critical. An ideal material for hemorrhage management does not require manual pressure to control bleeding, does not rely on the natural clotting cascade, is suitable for intracavitary hemorrhage, and is removed without debridement. A dissolvable dendritic thioester hydrogel sealant is described for intracavitary wounds. The hydrogel is composed of a lysine-based dendron and a PEG-based crosslinker, which are synthesized in high yields and subsequently characterized by 1H, 13C NMR spectroscopy, and MALDI. The hydrogel dissolution relies on a thiol–thioester exchange mechanism. When compared to untreated controls, the application of the hydrogel sealant reduces blood loss by 33% in a rat model of severe hepatic hemorrhage (23.57 ± 8.27 mL kg−1vs. 35.21 ± 7.47 mL kg−1; p = 0.02) and by 22% in a rat model of aortic injury (17.95 ± 3.84 mL kg−1vs. 23.09 ± 3.80 mL kg−1; p = 0.03). A unique feature of the hydrogel is its dissolution with a biocompatible solution following initial application – thus the treated wound area can be re-exposed for definitive surgical care in an operative setting.

Computed tomography-based rigidity analysis: a review of the approach in preclinical and clinical studies

The assessment of fracture risk in patients afflicted with osseous neoplasms has long presented a problem for orthopedic oncologists. These patients are at risk for developing pathologic fractures through lytic defects in the appendicular and axial skeleton with devastating consequences on their quality of life. Lesions with a high risk of fracture may require prophylactic surgical stabilization, whereas low-risk lesions can be treated conservatively. Therefore, effective prevention of pathologic fractures depends on accurate assessment of fracture risk and is a critical step to avoid debilitating complications. Given the complex nature of osseous neoplasms, treatment requires a multidisciplinary approach; yet, little consensus regarding fracture risk assessment exists among physicians involved in the care of these patients. In order to improve the overall standard of care, specific criteria must be adopted to formulate consistent and accurate fracture risk predictions. However, clinicians make subjective assessments about fracture risk on plain radiographs using guidelines now recognized to be inaccurate. Osseous neoplasms alter both the material and geometric properties of bone; failure to account for changes in both of these parameters limits the accuracy of current fracture risk assessments. Rigidity, the capacity to resist deformation upon loading, is a structural property that integrates both the material and geometric properties of bone. Therefore, rigidity can be used as a mechanical assay of the changes induced by lytic lesions to the structural competency of bone. Using this principle, computed tomography (CT)-based structural rigidity analysis (CTRA) was developed and validated in a series of preclinical and clinical studies.

Curved Beam Computed Tomography based Structural Rigidity Analysis of Bones with Simulated Lytic Defect: A Comparative Study with Finite Element Analysis

In this paper, a CT based structural rigidity analysis (CTRA) method that incorporates bone intrinsic local curvature is introduced to assess the compressive failure load of human femur with simulated lytic defects. The proposed CTRA is based on a three dimensional curved beam theory to obtain critical stresses within the human femur model. To test the proposed method, ten human cadaveric femurs with and without simulated defects were mechanically tested under axial compression to failure. Quantitative computed tomography images were acquired from the samples, and CTRA and finite element analysis were performed to obtain the failure load as well as rigidities in both straight and curved cross sections. Experimental results were compared to the results obtained from FEA and CTRA. The failure loads predicated by curved beam CTRA and FEA are in agreement with experimental results. The results also show that the proposed method is an efficient and reliable method to find both the location and magnitude of failure load. Moreover, the results show that the proposed curved CTRA outperforms the regular straight beam CTRA, which ignores the bone intrinsic curvature and can be used as a useful tool in clinical practices.

Hierarchical analysis and multi-scale modelling of rat cortical and trabecular bone.

The aim of this study was to explore the hierarchical arrangement of structural properties in cortical and trabecular bone and to determine a mathematical model that accurately predicts the tissues mechanical properties as a function of these indices. By using a variety of analytical techniques, we were able to characterize the structural and compositional properties of cortical and trabecular bones, as well as to determine the suitable mathematical model to predict the tissues mechanical properties using a continuum micromechanics approach. Our hierarchical analysis demonstrated that the differences between cortical and trabecular bone reside mainly at the micro- and ultrastructural levels. By gaining a better appreciation of the similarities and differences between the two bone types, we would be able to provide a better assessment and understanding of their individual roles, as well as their contribution to bone health overall.

In vivo kinetic evaluation of an adhesive capsulitis model in rats.

BACKGROUND AND HYPOTHESIS We hypothesized that extra-articular, internal fixation of the shoulder in rats would result in a subsequent decrease in rotational range of motion (ROM) and an increase in joint stiffness. We further hypothesized that residual kinematic changes would still be present at 8 weeks after immobilization. Extra-articular, internal fixation of the shoulder has been used to induce adhesive capsulitis in rats; however, the effects on in vivo kinematics have not been assessed. METHODS Baseline measurements of rotational torque and ROM were acquired (n = 10 rats), and the left forelimb of each animal was immobilized with sutures passed between the scapula and the humeral shaft. After 8 weeks, the sutures were removed, and changes in kinematics and kinetics were longitudinally quantified in the follow-up period. Changes in stiffness, defined as the area under the angle-torque curve, were also quantified. RESULTS Immediately after suture removal, there was a 63% decrease in total ROM compared with baseline (51° ± 10° vs. 136° ± 0°; P < .001). Similarly, total torque was found to increase 13.4 N.mm compared with baseline (22.6 ± 5.9 N.mm vs. 9.2 ± 2.6 N.mm; P = .002). Residual total ROM restrictions and an increased torque in internal rotation were still evident at 8 weeks of follow-up (113° ± 8° vs. 137° ± 0°, P < .001 and 3.5 ± 0.4 N.mm vs. 2.7 ± 0.7 N.mm, P = .036). Stiffness also increased after suture removal and at 8 weeks of follow-up compared with baseline. CONCLUSION This animal model of adhesive capsulitis rendered lasting effects on in vivo kinematics of the shoulder.

Rat Model of Adhesive Capsulitis of the Shoulder

This proposal aims to create an in vivo rat model of adhesive capsulitis for researching potential treatment options for this condition and other etiologies of comparable arthrofibrosis. The model includes extra-articular fixation of the shoulder in rats via scapular to humeral suturing, resulting in a secondary contracture without invading the intra-articular space and resulting in decreased rotational ROM and increased joint stiffness. We used 10 Sprague-Dawley rats for the purpose of this study. Baseline ROM measurements were taken before glenohumeral immobilization. The rats were subjected to 8 weeks of immobilization before the fixation sutures were removed and changes in ROM and joint stiffness were evaluated. To evaluate whether immobilization resulted in a significant reduction in ROM, changes in kinematics were calculated. ROM was measured at each time point in the follow-up period and was compared to the baseline internal and external ROM measurements. In order to evaluate the stiffness, joint kinetics were calculated by determining the differences in torque (text and tint ) needed to reach the initial external rotation of 60° and initial internal rotation of 80°. After the removal of the extra-articular suture fixation on follow-up day 0, we found a 63% decrease in total ROM compared to baseline. We observed continuous improvement until week 5 of follow-up, with the progress slowing down around a 19% restriction. On week 8 of follow-up, there was still an 18% restriction of ROM. Additionally, on follow-up day 0, we found the torque increased by 13.3 Nmm when compared to baseline. On week 8, the total torque was measured to be 1.4 ± 0.2 Nmm higher than initial measurements. This work introduces a rat model of shoulder adhesive capsulitis with lasting reduced ROM and increased stiffness.