Effect of decellularization on the load-bearing characteristics of articular cartilage matrix

The application of decellularized extracellular matrices to aid tissue regeneration in reconstructive surgery and regenerative medicine has been promising. Several decellularization protocols for removing cellular materials from natural tissues such as heart valves are currently in use. This paper evaluates the feasibility of potential extension of this methodology relative to the desirable properties of load bearing joint tissues such as stiffness, porosity and ability to recover adequately after deformation to facilitate physiological function. Two decellularization protocols, namely: Trypsin and Triton X-100 were evaluated against their effects on bovine articular cartilage, using biomechanical, biochemical and microstructural techniques. These analyses revealed that decellularization with trypsin resulted in severe loss of mechanical stiffness including deleterious collapse of the collagen architecture which in turn significantly compromised the porosity of the construct. In contrast, triton X-100 detergent treatment yielded samples that retain mechanical stiffness relative to that of the normal intact cartilage sample, but the resulting construct contained ruminant cellular constituents. We conclude that both of these common decellularization protocols are inadequate for producing constructs that can serve as effective replacement and scaffolds to regenerate articular joint tissue.

Feasibility of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold for cartilage tissue engineering

Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the current ECM materials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologous ECM scaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell-derived ECM (aBMSC-dECM) membrane was collected and fabricated into a three-dimensional porous scaffold via cross-linking and freeze-drying techniques. Articular chondrocytes were seeded into the aBMSC-dECM scaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that the aBMSC-dECM scaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in the aBMSC-dECM scaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on the aBMSC-dECM scaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that the aBMSC-dECM scaffold could be a successful novel candidate scaffold for cartilage tissue engineering.

Discussion of “Generalized estimating equations: Notes on the choice of the working correlation matrix”

Objective To discuss generalized estimating equations as an extension of generalized linear models by commenting on the paper of Ziegler and Vens "Generalized Estimating Equations. Notes on the Choice of the Working Correlation Matrix". Methods Inviting an international group of experts to comment on this paper. Results Several perspectives have been taken by the discussants. Econometricians have established parallels to the generalized method of moments (GMM). Statisticians discussed model assumptions and the aspect of missing data Applied statisticians; commented on practical aspects in data analysis. Conclusions In general, careful modeling correlation is encouraged when considering estimation efficiency and other implications, and a comparison of choosing instruments in GMM and generalized estimating equations, (GEE) would be worthwhile. Some theoretical drawbacks of GEE need to be further addressed and require careful analysis of data This particularly applies to the situation when data are missing at random.

Uncoupled surface spin induced exchange bias in α-MnO 2 nanowires

We have studied the microstructure, surface states, valence fluctuations, magnetic properties, and exchange bias effect in MnO2 nanowires. High purity α-MnO 2 rectangular nanowires were synthesized by a facile hydrothermal method with microwave-assisted procedures. The microstructure analysis indicates that the nanowires grow in the [0 0 1] direction with the (2 1 0) plane as the surface. Mn3+ and Mn2+ ions are not found in the system by X-ray photoelectron spectroscopy. The effective magnetic moment of the manganese ions fits in with the theoretical and experimental values of Mn4+ very well. The uncoupled spins in 3d3 orbitals of the Mn 4+ ions in MnO 6 octahedra on the rough surface are responsible for the net magnetic moment. Spin glass behavior is observed through magnetic measurements. Furthermore, the exchange bias effect is observed for the first time in pure α-MnO2 phase due to the coupling of the surface spin glass with the antiferromagnetic α-MnO2 matrix. These α-MnO2 nanowires, with a spin-glass-like behavior and with an exchange bias effect excited by the uncoupled surface spins, should therefore inspire further study concerning the origin, theory, and applicability of surface structure induced magnetism in nanostructures.

Edge of Danger: electric light and the negotiation of public and private domestic space in Philip Johnson's Glass and Guest House

In the first half of the twentieth century the dematerializing of boundaries between enclosure and exposure problematized traditional expectations of the domestic environment. At the same time, as a space of escalating technological control, the modern domestic interior also offered new potential to redefine the meaning and means of habitation. The inherent tension between these opposing forces is particularly evident in the introduction of new electric lighting technology and applications into the modern domestic interior in the mid-twentieth century. Addressing this nexus of technology and domestic psychology, this article examines the critical role of electric lighting in regulating and framing both the public and private occupation of Philip Johnson's New Canaan estate. Exploring the dialectically paired transparent Glass House and opaque Guest House, this study illustrates how Johnson employed electric light to negotiate the visual environment of the estate as well as to help sustain a highly aestheticized domestic lifestyle. Contextualized within the existing literature, this analysis provides a more nuanced understanding of the New Canaan estate as an expression of Johnson's interests as a designer as well as a subversion of traditional suburban conventions.

Illuminating the glass box: The lighting designs of Richard Kelly

A promotional brochure celebrating the completion of the Seagram Building in spring 1957 features on its cover intense portraits of seven men bisected by a single line of bold text that asks, “Who are these Men?” The answer appears on the next page: “They Dreamed of a Tower of Light” (Figures 1, 2). Each photograph is reproduced with the respective man’s name and project credit: architects, Mies van der Rohe and Philip Johnson; associate architect, Eli Jacques Kahn; electrical contractor, Harry F. Fischbach; lighting consultant, Richard Kelly; and electrical engineer, Clifton E. Smith. To the right, a rendering of the new Seagram Tower anchors the composition, standing luminous against a star-speckled night sky; its glass walls and bronze mullions are transformed into a gossamer skin that reveals the tower’s structural skeleton. Lightolier, the contract lighting manufacturer, produced the brochure to promote its role in the lighting of the Seagram Building, but Lightolier’s promotional copy was not far from the truth.

The Edge of Danger: artificial lighting and the dialectics of domestic occupation in Philip Johnson's Glass and Guest Houses

In the first half of the twentieth century the dematerializing of boundaries between enclosure and exposure problematized traditional acts of “occupation” and understandings of the domestic environment. As a space of escalating technological control, the modern domestic interior offered new potential to re-define the meaning and means of habitation. This shift is clearly expressed in the transformation of electric lighting technology and applications for the modern interior in the mid-twentieth century. Addressing these issues, this paper examines the critical role of electric lighting in regulating and framing both the public and private occupation of Philip Johnson’s New Canaan estate. Exploring the dialectically paired transparent Glass House and opaque Guest House (both 1949), this study illustrates how Johnson employed artificial light to control the visual environment of the estate as well as to aestheticize the performance of domestic space. Looking closely at the use of artificial light to create emotive effects as well as to intensify the experience of occupation, this revisiting of the iconic Glass House and lesser-known Guest House provides a more complex understanding of Johnson’s work and the means with which he inhabited his own architecture. Calling attention to the importance of Johnson serving as both architect and client, and his particular interest in exploring the new potential of architectural lighting in this period, this paper investigates Johnson’s use of electric light to support architectural narratives, maintain visual order and control, and to suit the nuanced desires of domestic occupation.

3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments

Interactions between tumour cells and extracellular matrix proteins of the tumour microenvironment play crucial roles in cancer progression. So far, however, there are only a few experimental platforms available that allow us to study these interactions systematically in a mechanically defined three-dimensional (3D) context. Here, we have studied the effect of integrin binding motifs found within common extracellular matrix (ECM) proteins on 3D breast (MCF-7) and prostate (PC-3, LNCaP) cancer cell cultures, and co-cultures with endothelial and mesenchymal stromal cells. For this purpose, matrix metalloproteinase-degradable biohybrid poly(ethylene) glycol-heparin hydrogels were decorated with the peptide motifs RGD, GFOGER (collagen I), or IKVAV (laminin-111). Over 14 days, cancer spheroids of 100-200µm formed. While the morphology of poorly invasive MCF-7 and LNCaP cells was not modulated by any of the peptide motifs, the aggressive PC-3 cells exhibited an invasive morphology when cultured in hydrogels comprising IKVAV and GFOGER motifs compared to RGD motifs or nonfunctionalised controls. PC-3 (but not MCF-7 and LNCaP) cell growth and endothelial cell infiltration were also significantly enhanced in IKVAV and GFOGER presenting gels. Taken together, we have established a 3D culture model that allows for dissecting the effect of biochemical cues on processes relevant to early cancer progression. These findings provide a basis for more mechanistic studies that may further advance our understanding of how ECM modulates cancer cell invasion and how to ultimately interfere with this process.