SPECT/CT Assessment of In-Vivo Loading of the Knee Correlates with Polyethylene Deformation in Retrieved Total Knee Arthroplasty

Background: SPECT/CT distribution patterns in patients with total knee replacements have previously been correlated with factors such as time of implantation, implant type and alignment. It is unknown, however, if an increased and more extended bone tracer uptake (BTU) in SPECT/CT, representing loading of the joint, correlates with findings from retrieval studies. The aim of this study was to further understand this subject. Materials and Methods: 62 retrieved TKA were included. SPECT/CT was performed prior to revision. Quantitative and qualitative medio-lateral comparisons of BTU intensity and distribution in the tibia were performed. Retrieval analysis was performed with a micro-CT method to assess the thickness differences between medial and lateral sides of polyethylene inserts with symmetrical designs. Results: In the subgroup of TKA with asymmetrical SPECT/CT distribution, there was a significant correlation between retrieval and medical imaging data (p = 0.0355): patients showing a more extended BTU in the medial compartment also had a significantly thinner insert in the medial compartment, and vice versa in the lateral side. Conclusion: This is the first study comparing BTU distribution patterns and retrieval findings. Our results support the hypothesis that SPECT/CT is able to identify bone activity due to implant position and loading.

Osteocytic Pericellular Matrix (PCM): Accelerated Degradation under In Vivo Loading and Unloading Conditions Using a Novel Imaging Approach

The proteoglycan-containing pericellular matrix (PCM) controls both the biophysical and biochemical microenvironment of osteocytes, which are the most abundant cells embedded and dispersed in bones. As a molecular sieve, osteocytic PCMs not only regulate mass transport to and from osteocytes but also act as sensors of external mechanical environments. The turnover of osteocytic PCM remains largely unknown due to technical challenges. Here, we report a novel imaging technique based on metabolic labeling and “click-chemistry,” which labels de novo PCM as “halos” surrounding osteocytes in vitro and in vivo. We then tested the method and showed different labeling patterns in young vs. old bones. Further “pulse-chase” experiments revealed dramatic difference in the “half-life” of PCM of cultured osteocytes (~70 h) and that of osteocytes in vivo (~75 d). When mice were subjected to either 3-week hindlimb unloading or 7-week tibial loading (5.1 N, 4 Hz, 3 d/week), PCM half-life was shortened (~20 d) and degradation accelerated. Matrix metallopeptidase MMP-14 was elevated in mechanically loaded osteocytes, which may contribute to PCM degradation. This study provides a detailed procedure that enables semi-quantitative study of the osteocytic PCM remodeling in vivo and in vitro.

Tendon mechanobiology in small-animal experiments during post-transection healing

Ruptures to tendons are common and costly, and no clinical consensus exists on the appropriate treatment and rehabilitation regimen to promote their healing as well as full recovery of functionality. Although mechanobiology is known to play an important role in tendon regeneration, the understanding of how mechano-regulated processes affect tendon healing needs further clarification. Many small-animal studies, particularly in rats and mice, have characterized the progression of healing in terms of geometrical, structural, compositional, mechanical, and cellular properties. Some of the properties are also studied under different mechanical loading regimens. The focus of this review is to summarize and generalize the information in the literature regarding spatial and temporal differentiation of tendon properties during rodent tendon healing following full-tendon transection, as well as how this is affected by altered in vivo loading regimens.

Effects of volumetric boundary conditions on the compressive mechanics and modeling of passive skeletal muscle

For over two decades, computational models of human body—such as the Toyota THUMS model— have been used in automobilesafety. These models rely on accurate material properties for eachtissue. However, the compressive behavior of skeletal muscle is notfully understood, particularly regarding the differences in muscleresponse to in vivo loading conditions. It is likely that in vivo muscleexperiences a variation between confined and unconfined volumetricboundary conditions, but nearly all previous studies investigatingpassively compressed tissue have focused on muscle in unconfinedcompression (UC). One study has investigated muscle underanisotropic semi-confined compression, however none have studiedmuscle in fully confined compression (CC). Thus, we have investigatedthe effects of volumetric boundary conditions (UC and CC) on the stressrelaxation of skeletal muscle. Moreover, a finite element modelsimultaneously characterizing muscle behavior in both boundaryconditions is explored.

Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility

Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.

Molecular Basis for Periodontal Ligament Adaptation to In Vivo Loading

A soft food diet leads to changes in the periodontal ligament (PDL). These changes, which have been recognized for more than a century, are ascribed to alterations in mechanical loading. While these adaptive responses have been well characterized, the molecular, cellular, and mechanical mechanisms underlying the changes have not. Here, we implicate Wnt signaling in the pathoetiology of PDL responses to underloading. We show that Wnt-responsive cells and their progeny in the PDL space exhibit a burst in proliferation in response to mastication. If an animal is fed a soft diet from the time of weaning, then this burst in Wnt-responsive cell proliferation is quelled; as a consequence, both the PDL and the surrounding alveolar bone undergo atrophy. Returning these animals to a hard food diet restores the Wnt signaling in PDL. These data provide, for the first time, a molecular mechanism underlying the adaptive response of the PDL to loading.