Promoting Equity, Diversity and Social Justice Through Faculty-Led Transformative Projects.

We present a transformative professional development project with a focus on equity, diversity and social justice (EDSJ) to raise cultural awareness among faculty, increase agency, and promote positive change through transformative projects. Twenty-three faculty members from nine different colleges located at a Research I university were provided with critical cultural awareness workshops and then supported to develop transformative projects related to EDSJ. Based on focus group interviews and pre-post surveys, we identified four themes and five categories: two outcome-related (Building Community and Transformative Actions) and two operational themes (Barriers and Facilitators). We conclude that faculty-centered and transformative professional development projects could significantly benefit all those interested in establishing a culturally inclusive, positive and responsive climate. Our study also contributes to the emerging research on scholar activism and provides a practical model for implementation.

Prediction of equibiaxial loading stress in collagen-based extracellular matrix using a three-dimensional unit cell model.

Mechanical signals are important factors in determining cell fate. Therefore, insights as to how mechanical signals are transferred between the cell and its surrounding three-dimensional collagen fibril network will provide a basis for designing the optimum extracellular matrix (ECM) microenvironment for tissue regeneration. Previously we described a cellular solid model to predict fibril microstructure-mechanical relationships of reconstituted collagen matrices due to unidirectional loads (Acta Biomater 2010;6:1471-86). The model consisted of representative volume elements made up of an interconnected network of flexible struts. The present study extends this work by adapting the model to account for microstructural anisotropy of the collagen fibrils and a biaxial loading environment. The model was calibrated based on uniaxial tensile data and used to predict the equibiaxial tensile stress-stretch relationship. Modifications to the model significantly improved its predictive capacity for equibiaxial loading data. With a comparable fibril length (model 5.9-8µm, measured 7.5µm) and appropriate fibril anisotropy the anisotropic model provides a better representation of the collagen fibril microstructure. Such models are important tools for tissue engineering because they facilitate prediction of microstructure-mechanical relationships for collagen matrices over a wide range of microstructures and provide a framework for predicting cell-ECM interactions.

Development of a three-dimensional unit cell to model the micromechanical response of a collagen-based extracellular matrix.

The three-dimensional microstructure and mechanical properties of the collagen fibrils within the extracellular matrix (ECM) is now being recognized as a primary factor in regulating cell proliferation and differentiation. Therefore, an appreciation of the mechanical aspects by which a cell interacts with its ECM is required for the development of engineered tissues. Ultimately, using these interactions to design tissue equivalents requires mathematical models with three-dimensional architecture. In this study, a three-dimensional model of a collagen fibril matrix undergoing uniaxial tensile stress was developed by making use of cellular solids. A structure consisting of thin struts was chosen to represent the arrangement of collagen fibrils within an engineered ECM. To account for the large deformation of tissues, the collagen fibrils were modeled as hyperelastic neo-Hookean or Mooney-Rivlin materials. The use of cellular solids allowed the fibril properties to be related to the ECM properties in closed form, which, in turn, allowed the estimation of fibril properties using ECM experimental data. A set of previously obtained experimental data consisting of simultaneous measures of the fibril microstructure and mechanical tests was used to evaluate the model's capability to estimate collagen fibril mechanical property when given tissue-scale data and to predict the tissue-scale mechanical properties when given estimated fibril stiffness. The fibril tangent modulus was found to be 1.26 + or - 0.70 and 1.62 + or - 0.88 MPa when the fibril was modeled as neo-Hookean and Mooney-Rivlin material, respectively. There was no statistical significance of the estimated fibril tangent modulus among the different groups. Sensitivity analysis showed that the fibril mechanical properties and volume fraction were the two input parameters which required accurate values. While the volume fraction was easily obtained from the initial image of the gel, the fibril mechanical properties were not readily available. Therefore the fibril mechanical properties were estimated in the leave-one-out cross-validation (LOOCV) analysis. The LOOCV analysis showed that the model was able to predict the ECM stress-stretch curve with an average mean squared error of 9.71 kPa(2). The three-dimensional architecture expands on previous continuum models and two-dimensional representations to provide a useful model for studying the hierarchical effects of ECM microstructure on cell function. This model can be used as a design tool to engineer the optimum microstructure for cells to function.

Fibril microstructure affects strain transmission within collagen extracellular matrices.

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.

A comparison of suture retention strengths for three biomaterials.

BACKGROUND: The suture holding capacity, suture retention strength, and burst strength of three biomaterials (Marlex), SIS, and PeriGuard) were evaluated to compare their performance characteristics in an ex vivo setting representing the immediate postoperative period. MATERIAL/METHODS: A circular defect was created in the fascial tissue of the abdominal aponeurosis collected from normal dogs. Defects were repaired with either Marlex (polypropylene mesh), Periguard (bovine pericardium) or small intestinal submucosa (SIS) using 2-0 prolene and a 1.0-cm suture bite. The force required to induce failure at the repair site was recorded as the suture-holding capacity. Suture retention strength was calculated as the load distribution over the specimen cross-section in contact with the suture at the time of rupture. Burst strength of the raw materials was also measured. RESULTS: The suture-holding capacity was 370.9+/-56.2 N for Marlex; 214.3+/-36.1 N for Periguard, and 287.9+/-34.3 N for SIS. The suture retention strengths were: Marlex, 413.4+/-59.7 N/mm2; Periguard, 97.0+/-20.1 N/mm2; and SIS, 106.9+/-12.7 N/mm2. The burst strength of Marlex, Periguard and SIS were 476.7+/-50.8 N, 432.12+/-82.1 N, and 433.6+/-79.5 N respectively. CONCLUSIONS: All three materials provide adequate strength and suture-holding capacities to be of use in the repair of soft tissue defects.

Local, three-dimensional strain measurements within largely deformed extracellular matrix constructs.

The ability to create extracellular matrix (ECM) constructs that are mechanically and biochemically similar to those found in vivo and to understand how their properties affect cellular responses will drive the next generation of tissue engineering strategies. To date, many mechanisms by which cells biochemically communicate with the ECM are known. However the mechanisms by which mechanical information is transmitted between cells and their ECM remain to be elucidated. "Self-assembled" collagen matrices provide an in vitro-model system to study the mechanical behavior of ECM. To begin to understand how the ECM and the cells interact mechanically, the three-dimensional (3D) mechanical properties of the ECM must be quantified at the micro-(local) level in addition to information measured at the macro-(global) level. Here we describe an incremental digital volume correlation (IDVC) algorithm to quantify large (>0.05) 3D mechanical strains in the microstructure of 3D collagen matrices in response to applied mechanical loads. Strain measurements from the IDVC algorithm rely on 3D confocal images acquired from collagen matrices under applied mechanical loads. The accuracy and the precision of the IDVC algorithm was verified by comparing both image volumes collected in succession when no deformation was applied to the ECM (zero strain) and image volumes to which simulated deformations were applied in both ID and 3D (simulated strains). Results indicate that the IDVC algorithm can accurately and precisely determine the 3D strain state inside largely deformed collagen ECMs. Finally, the usefulness of the algorithm was demonstrated by measuring the microlevel 3D strain response of a collagen ECM loaded in tension.

Morphologic study of small intestinal submucosa as a body wall repair device.

BACKGROUND: The extracellular matrix (ECM) derived from porcine small intestinal submucosa (SIS) has been used as a constructive scaffold for tissue repair in both preclinical animal studies and human clinical trials. Quantitative characterization of the host tissue response to this xenogeneic scaffold material has been lacking. MATERIALS AND METHODS: The morphologic response to a multilaminate form of the SIS-ECM was evaluated in a chronic, 2-year study of body wall repair in two separate species: the dog and the rat. Morphologic response to the SIS-ECM was compared to that for three other commonly used bioscaffold materials including Marlex mesh, Dexon, and Perigard. Quantitative measurements were made of tissue consistency, polymorphonuclear cell response, mononuclear cell response, tissue organization, and vascularity at five time points after surgical implantation: 1 week, 1, 3, and 6 months, and 2 years. RESULTS: All bioscaffold materials functioned well as a repair device for large ventral abdominal wall defects created in these two animal models. The SIS-ECM bioscaffold showed a greater number of polymorphonuclear leukocytes at the 1-week time point and a greater degree of graft site tissue organization after 3 months compared to the other three scaffold materials. There was no evidence for local infection or other detrimental local pathology to any of the graft materials at any time point. CONCLUSIONS: Like Marlex, Dexon, and Perigard, the SIS-ECM is an effective bioscaffold for long-term repair of body wall defects. Unlike the other scaffold materials, the resorbable SIS-ECM scaffold was replaced by well-organized host tissues including differentiated skeletal muscle.

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

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.

Simultaneous mechanical loading and confocal reflection microscopy for three-dimensional microbiomechanical analysis of biomaterials and tissue constructs.

At present, mechanisms by which specific structural and mechanical properties of the three-dimensional extracellular matrix microenvironment influence cell behavior are not known. Lack of such knowledge precludes formulation of engineered scaffolds or tissue constructs that would deliver specific growth-inductive signals required for improved tissue restoration. This article describes a new mechanical loading-imaging technique that allows investigations of structural-mechanical properties of biomaterials as well as the structural-mechanical basis of cell-scaffold interactions at a microscopic level and in three dimensions. The technique is based upon the integration of a modified, miniature mechanical loading instrument with a confocal microscope. Confocal microscopy is conducted in a reflection and/or fluorescence mode for selective visualization of load-induced changes to the scaffold and any resident cells, while maintaining each specimen in a "live," fully hydrated state. This innovative technique offers several advantages over current biomechanics methodologies, including simultaneous visualization of scaffold and/or cell microstructure in three dimensions during mechanical loading; quantification of macroscopic mechanical parameters including true stress and strain; and the ability to perform multiple analyses on the same specimen. This technique was used to determine the structural-mechanical properties of three very different biological materials: a reconstituted collagen matrix, a tissue-derived biomaterial, and a tissue construct representing cells and matrix.