In this study, we propose a method for quantitative prediction of changes in concentrations of a number of key signaling, structural and effector molecules within the extracellular matrix of tendon. To achieve this, we introduce the notion of elementary cell responses (ECRs). An ECR defines a normal reference secretion profile of a molecule by a tenocyte in response to the tenocyte's local strain. ECRs are then coupled with a model for mechanical damage of tendon collagen fibers at different straining conditions of tendon and then scaled up to the tendon tissue level for comparison with experimental observations. Specifically, our model predicts relative changes in ECM concentrations of transforming growth factor beta, interleukin 1 beta, collagen type I, glycosaminoglycan, matrix metalloproteinase 1 and a disintegrin and metalloproteinase with thrombospondin motifs 5, with respect to tendon straining conditions that are consistent with the observations in the literature. In good agreement with a number of in vivo and in vitro observations, the model provides a logical and parsimonious explanation for how excessive mechanical loading of tendon can lead to under-stimulation of tenocytes and a degenerative tissue profile, which may well have bearing on a better understanding of tendon homeostasis and the origin of some tendinopathies.
While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model. Using a stochastic model of fiber repair, it is assumed that mechanically damaged fibers are repaired longer, whereas proteolytically damaged fibers are repaired shorter, relative to their pre-damage length. To study adaptation of tendon properties to applied load, our model musculotendon unit is a simplified three-component Hill-type model of the human Achilles-soleus unit. Our model results demonstrate that the geometric equilibrium state of the Achilles tendon can coincide with minimization of the total metabolic cost of muscle activation. The proposed tendon model independently predicts rates of collagen fiber turnover that are in general agreement with in vivo experimental measurements. While the computational model here only represents a first step in a new approach to understanding the complex process of tendon remodeling in vivo, given these findings, it appears likely that the proposed framework may itself provide a useful theoretical foundation for developing valuable qualitative and quantitative insights into tendon physiology and pathology.
Stents are artificial implants that provide scaffolding to a cavity inside the body. This paper presents a new luminal device for reducing the mechanical failure of stents due to recoil, which is one of the most important issues in stenting. This device, which we call a recoil-resilient ring (RRR), is utilized standalone or potentially integrated with existing stents to address the problem of recoil. The proposed structure aims to minimize the need for high-pressure overexpansion that can induce intra-luminal trauma and excess growth of vascular tissue causing later restenosis. The RRR is an overlapped open ring with asymmetrical sawtooth structures that are intermeshed. These teeth can slide on top of each other, while the ring is radially expanded, but interlock step-by-step so as to keep the final expanded state against compressional forces that normally cause recoil. The RRRs thus deliver balloon expandability and, when integrated with a stent, bring both radial rigidity and longitudinal flexibility to the stent. The design of the RRR is investigated through finite element analysis (FEA), and then the devices are fabricated using micro-electro-discharge machining of 200-μm-thick Nitinol sheet. The standalone RRR is balloon expandable in vitro by 5-7 Atm in pressure, which is well within the recommended in vivo pressure ranges for stenting procedures. FEA compression tests indicate 13 × less reduction of the cross-sectional area of the RRR compared with a typical stainless steel stent. These results also show perfect elastic recovery of the RRR after removal of the pressure compared to the remaining plastic deformations of the stainless steel stent. On the other hand, experimental loading tests show that the fabricated RRRs have 2.8 × radial stiffness compared to a two-column section of a commercial stent while exhibiting comparable elastic recovery. Furthermore, testing of in vitro expansion in a mock artery tube shows around 2.9% recoil, approximately 5-11 × smaller than the recoil reported for commercial stents. These experimental results demonstrate the effectiveness of the device design for the targeted luminal support and stenting applications.
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