https://www.seas.upenn.edu/%7Edischer/pdfs/Cell_on_Gel-CELLpaper.pdf

Matrix elasticity directs stem cell lineage specification.

Gold, enigmatically represented by the target-like design of its ancient alchemical symbol, has been considered a mystical material of great value for centuries. Nanoscale particles of gold now command a great deal of attention for biomedical applications. Depending on their size, shape, degree of aggregation, and local environment, gold nanoparticles can appear red, blue, or other colors. These visible colors reflect the underlying coherent oscillations of conduction-band electrons (“plasmons”) upon irradiation with light of appropriate wavelengths. These plasmons underlie the intense absorption and elastic scattering of light, which in turn forms the basis for many biological sensing and imaging applications of gold nanoparticles. The brilliant elastic light-scattering properties of gold nanoparticles are sufficient to detect individual nanoparticles in a visible light microscope with ∼102 nm spatial resolution. Despite the great excitement about the potential uses of gold nanoparticles for medical diag...

Gold nanoparticles in biology: beyond toxicity to cellular imaging

Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0°, 90°, 43° and −43°, with respect to the axial direction of the artery, and corresponding circular standard deviations of 40°, 47°, 37° and 37°. The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cut-open). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wall.

/pdf/experimental-investigation-of-collagen-waviness-and-35sv8tu15v.pdf

Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy.

Fibroblast biology in three-dimensional collagen matrices.

The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues.

Scaffold Design for Bone Regeneration

The importance and priority of specific micro-structural and mechanical design parameters must be established to effectively engineer scaffolds (biomaterials) that mimic the extracellular matrix (ECM) environment of cells and have clinical applications as tissue substitutes. In this study, three-dimensional (3-D) matrices were prepared from type I collagen, the predominant compositional and structural component of connective tissue ECMs, and structural-mechanical relationships were studied. Polymerization conditions, including collagen concentration (0.3-3 mg/mL) and pH (6-9), were varied to obtain matrices of collagen fibrils with different microstructures. Confocal reflection microscopy was used to assess specific micro-structural features (e.g., diameter and length) and organization of component fibrils in 3-D. Microstructural analyses revealed that changes in collagen concentration affected fibril density while maintaining a relatively constant fibril diameter. On the other hand, both fibril length and diameter were affected by the pH of the polymerization reaction. Mechanically, all matrices exhibited a similar stress-strain curve with identifiable "toe," "linear," and "failure" regions. However the linear modulus and failure stress increased with collagen concentration and were correlated with an increase in fibril density. Additionally, both the linear modulus and failure stress showed an increase with pH, which was related to an increasedfibril length and a decreasedfibril diameter. The tensile mechanical properties of the collagen matrices also showed strain rate dependence. Such fundamental information regarding the 3-D microstructural-mechanical properties of the ECM and its component molecules are important to our overall understanding of cell-ECM interactions (e.g., mechanotransduction) and the development of novel strategies for tissue repair and replacement.

/pdf/tensile-mechanical-properties-of-three-dimensional-type-i-1xfhekm58n.pdf

Tensile mechanical properties of three-dimensional type I collagen extracellular matrices with varied microstructure.

Global experience with an inner branched arch endograft.

Branched versus fenestrated endografts for endovascular repair of aortic arch lesions

The disclosure relates to an intraluminal medical device. The medical device comprises a main graft, a first extension graft, and a second extension graft. The main graft comprises a proximal end, a distal end, and a body extending between the proximal end and distal end. The distal end of the main graft comprises a first branch and a second branch, the branches extending distally from the body. The first and second extension grafts comprise at least one stent and have a body reinforcing portion and a branch reinforcing portion. The body reinforcing portions have a larger expanded dimension than the expanded dimension of the respective branch reinforcing portion. The body reinforcing portions, together, have an expanded dimension that is generally equal to the expanded dimension of the outer graft body.

Low profile medical device

The next generation of medical devices and engineered tissues will require development of scaffolds that mimic the structural and functional properties of the extracellular matrix (ECM) component of tissues. Unfortunately, little is known regarding how ECM microstructure participates in the transmission of mechanical load information from a global (tissue or construct) level to a level local to the resident cells ultimately initiating relevant mechanotransduction pathways. In this study, the transmission of mechanical strains at various functional levels was determined for three-dimensional (3D) collagen ECMs that differed in fibril microstructure. Microstructural properties of collagen ECMs (e.g., fibril density, fibril length, and fibril diameter) were systematically varied by altering in vitro polymerization conditions. Multiscale images of the 3D ECM macro- and microstructure were acquired during uniaxial tensile loading. These images provided the basis for quantification and correlation of strains at global and local levels. Results showed that collagen fibril microstructure was a critical determinant of the 3D global and local strain behaviors. Specifically, an increase in collagen fibril density reduced transverse strains in both width and thickness directions at both global and local levels. Similarly, collagen ECMs characterized by increased fibril length and decreased fibril diameter exhibited increased strain in width and thickness directions in response to loading. While extensional strains measured globally were equivalent to applied strains, extensional strains measured locally consistently underpredicted applied strain levels. These studies demonstrate that regulation of collagen fibril microstructure provides a means to control the 3D strain response and strain transfer properties of collagen-based ECMs.

Blayne A. Roeder

Papers

Tensile mechanical properties of three-dimensional type I collagen extracellular matrices with varied microstructure.

Global experience with an inner branched arch endograft.

Branched versus fenestrated endografts for endovascular repair of aortic arch lesions

Low profile medical device

Fibril Microstructure Affects Strain Transmission Within Collagen Extracellular Matrices