Comparison of 2-D Fiber Network Orientation Measurement Methods

Author(s):  
Edward A. Sander ◽  
Victor H. Barocas

The mechanical properties of most soft tissues are dependent on the underlying network of collagen fibers, proteoglycans, and other extracellular matrix components [1]. Similarly, the properties of in vitro tissue analogs, often created from collagen or fibrin gels, are also dependent on the organization of the biopolymers within [2]. In both materials, the overall mechanical response is inherently multi-scale and dynamic. To understand the interplay between scales a satisfactory description of the microstructure must be obtained that is both tractable for modeling purposes and faithful to the essential physics of the tissue.

Author(s):  
Xiaoyue Ma ◽  
J. Edward Green ◽  
Keith J. Gooch ◽  
Rebecca M. Jansen ◽  
Richard T. Hart

Collagen is an important structural protein in the human body, and its molecules form structural aggregates at multiple length scales (i.e., microfibrils, fibrils, fibers, and bundles of different sizes) in biological tissues and organs [1]. The mechanical properties of most tissues are dependent on the underlying network of collagen fibers, proteoglycans, and other extracellular matrix components [2]. Similarly, the properties of in vitro tissue analogs, often created from collagen or fibrin gels, are also dependent on the organization of the biopolymers [3]. The overall mechanical response is intrinsically multi-scale and dynamic in both materials. As a result, a satisfactory description of the microstructure is important for exploring the essential physics of the tissue.


Author(s):  
Lijuan Zhang ◽  
Spencer P. Lake ◽  
Victor K. Lai ◽  
Victor H. Barocas ◽  
Mark S. Shephard

The mechanical properties of soft connective tissues are governed by their collagen fiber network and surrounding non-fibrillar matrix (e.g., proteoglycans, cells, elastin, etc.). In order to understand how healthy tissues function, and how properties change in injury and disease, it is necessary to quantify the mechanical response of both the collagen network and the non-fibrillar matrix (NFM), as well as the nature of the interaction between these tissue constituents. Using collagen-agarose co-gels as a simple experimental tissue analog system, we have demonstrated how NFM contributes to the mechanical and organizational properties of soft tissues in indentation and tension [1–2]. Furthermore, we used a network-based microscale model to examine how specific NFM properties alter the response of fiber-matrix composites under load [3]. This model fit our experimental data well and provided insight into the role of NFM in tensile mechanics. Since it was constructed according to the conventional approach of superposition of the two constituents (collagen network and NFM), however, the model could not specifically examine local interactions between collagen fibers and the surrounding NFM, which could be critical in assessing tissue damage or cell-matrix interactions. Therefore, we developed and evaluated a fiber-matrix modeling scheme to characterize the microstructural interactions between tissue constituents, as well as to quantify the role of individual tissue components in the behavior of soft tissues under tensile load. For validation, the new model (‘coupled’) was compared to our previous model (‘parallel’) and to experimental co-gel data.


Author(s):  
Woojin M. Han ◽  
Nandan L. Nerurkar ◽  
Lachlan J. Smith ◽  
Nathan T. Jacobs ◽  
Robert L. Mauck ◽  
...  

The annulus fibrosus (AF) is a multi-lamellar fibrocartilagenous ring in the intervertebral disc. The variation of biochemical composition from the outer to the inner AF is largely responsible for the heterogeneous mechanical properties. In vitro tissue-level studies require mechanical testing in aqueous buffers to avoid tissue dehydration. The varying glycosaminoglycan (GAG) contents from outer to inner AF suggest that the response to high and low PBS osmolarity may also be different with radial position. Previous studies in tendon and ligament have been conflicting: soaking tendon fascicles in PBS decreased tensile modulus1 and treating ligament in buffer had no effect on modulus.2


Author(s):  
G. Puglisi ◽  
G. Saccomandi

We survey, in a partial way, multi-scale approaches for the modelling of rubber-like and soft tissues and compare them with classical macroscopic phenomenological models. Our aim is to show how it is possible to obtain practical mathematical models for the mechanical behaviour of these materials incorporating mesoscopic (network scale) information. Multi-scale approaches are crucial for the theoretical comprehension and prediction of the complex mechanical response of these materials. Moreover, such models are fundamental in the perspective of the design, through manipulation at the micro- and nano-scales, of new polymeric and bioinspired materials with exceptional macroscopic properties.


Author(s):  
Todd D. Courtney ◽  
Jun Liao ◽  
William R. Wagner ◽  
Michael S. Sacks

For most tissue engineering applications that seek to generate tissue de novo, the scaffold is the first step in a series of important developmental considerations. Whether synthetic or natural, scaffolds developed for immediate in vivo use must have mechanical properties comparable to the native tissue for at least the minimum time necessary for the accompanying seeded cells, and eventual cells that migrate in, to lay down an equivalent supporting matrix. Scaffolds developed for the purpose of growing a tissue in vitro, with eventual in vivo use, need not necessarily meet these mechanical requirements. However, to better develop new tissues in bioreactors or in vivo, it is pertinent to understand how the fiber network changes under some regimen of mechanical load, in essence to understand what the cell witnesses within the scaffold. Extending our previous work, which focused on measuring and modeling the mechanical response of electrospun poly ester urethane urea (es-PEUU) scaffolds [1], we investigated the intricate and detailed es-PEUU fiber networks that are created during scaffold synthesis and how these networks change under various levels of strain. Specifically, we focused on several scaffold responses to strain: 1) Characteristics of fiber tortuosity, which when increased can yield delayed onset of scaffold stiffness as well as other varying mechanical responses. 2) Fiber splay, which determines the orientation of the all fibers within the scaffold. 3) Local vs global strain analysis to determine whether the scaffolds follow affine or non-affine deformations. 4) Fiber strain, to investigate how increasing levels of scaffold strain are transmitted to local fibers. 5) Changes in fiber tortuosity and overall fiber directions under strain.


Author(s):  
Eric M. Christiansen ◽  
Mohammad F. Hadi ◽  
Victor H. Barocas

Soft tissues are comprised of underlying fiber networks of collagen and other fibrous proteins and biopolymers. Thus, the ability to model the deformation of fiber networks is critical to understanding the mechanics of tissues in vivo and in vitro [1]. Complicating the issue, protein fiber networks are comprised of a range of different topologies that behave differently under load. There is a clear need for a method to derive network parameters that characterize the network and allow for the prediction of their behavior. In this study, we characterized several different random fiber network types based on their intrinsic mechanical and topological properties. Such characterization would improve our ability to select microscale network topologies that match the mechanical properties we observe in healthy and diseased native tissues [2]. It would also improve our ability to discern the outcome of microstructural changes in tissues (such as from remodeling or injury) on their overall mechanics.


Author(s):  
Yasushi P. Kato ◽  
Michael G. Dunn ◽  
Frederick H. Silver ◽  
Arthur J. Wasserman

Collagenous biomaterials have been used for growing cells in vitro as well as for augmentation and replacement of hard and soft tissues. The substratum used for culturing cells is implicated in the modulation of phenotypic cellular expression, cellular orientation and adhesion. Collagen may have a strong influence on these cellular parameters when used as a substrate in vitro. Clinically, collagen has many applications to wound healing including, skin and bone substitution, tendon, ligament, and nerve replacement. In this report we demonstrate two uses of collagen. First as a fiber to support fibroblast growth in vitro, and second as a demineralized bone/collagen sponge for radial bone defect repair in vivo.For the in vitro study, collagen fibers were prepared as described previously. Primary rat tendon fibroblasts (1° RTF) were isolated and cultured for 5 days on 1 X 15 mm sterile cover slips. Six to seven collagen fibers, were glued parallel to each other onto a circular cover slip (D=18mm) and the 1 X 15mm cover slip populated with 1° RTF was placed at the center perpendicular to the collagen fibers. Fibroblast migration from the 1 x 15mm cover slip onto and along the collagen fibers was measured daily using a phase contrast microscope (Olympus CK-2) with a calibrated eyepiece. Migratory rates for fibroblasts were determined from 36 fibers over 4 days.


2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.


2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.


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