Building Entrepreneurial Mindset: Motivating Curiosity, Connections, and Creating Value in an Assistive-Device Design Project.

Developing entrepreneurial mindset (EM) can help students understand the bigger picture, recognize opportunities, and learn from mistakes to create value. The purpose of this work was to promote EM development in a required junior-level mechanical engineering course. A pre-existing assistive device project was adapted to incorporate entrepreneurial-minded learning activities requiring students to demonstrate curiosity, make connections, and create value. The project was completed across the entire semester. Students created photojournals and participated in activities to build empathy for project clients. Value propositions were developed and presented before the course content was applied to design and evaluate assistive devices. At the conclusion of the project, the students reported high self-efficacy with the EM-related project objectives.

Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells.

BACKGROUND: Collagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model. METHODS: Collagen-HA scaffolds and collagen-only scaffolds were fabricated as previously described, and a clinically approved bone void filler was used as a control for the material. Constructs were seeded with hASCs and were pre-treated with either control or osteogenic media. A cell-free group was also included. Scaffolds were implanted subcutaneously in the backs of athymic nude mice for 8 weeks. Mineral deposition was quantified via micro-computed tomography. Histological and immunofluorescence images of the explants were used to analyze their vascular invasion, remodeling and cellularity. RESULTS: Cell-free collagen-HA scaffolds and those that were pre-seeded with osteogenically differentiated hASCs supported mineral deposition and vascular invasion at comparable rates, while cell-seeded constructs treated with the control medium showed lower mineralization after implantation. HA-reinforcement allowed collagen constructs to maintain their shape, provided improved cell-tissue-scaffold integration, and resulted in a more organized tissue when pre-treated in an osteogenic medium. Scaffold type and pre-treatment also determined osteoclast activity and therefore potential remodeling of the constructs. CONCLUSIONS: The results of this study cumulatively indicate that treatment medium and scaffold composition direct mineralization and angiogenic tissue formation in an ectopic model. The data suggest that it may be necessary to match the scaffold with a particular cell type and cell-specific pre-treatment to achieve optimal bone formation.

Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties.

Hydroxyapatite (HA) reinforced collagen scaffolds have shown promise for synthetic bone graft substitutes and tissue engineering scaffolds. Freeze-dried HA-collagen scaffolds are readily fabricated and have exhibited osteogenicity in vivo, but are limited by an inherent scaffold architecture that results in a relatively small pore size and weak mechanical properties. In order to overcome these limitations, HA-collagen scaffolds were prepared by compression molding HA reinforcements and paraffin microspheres within a suspension of concentrated collagen fibrils (∼ 180 mg/mL), cross-linking the collagen matrix, and leaching the paraffin porogen. HA-collagen scaffolds exhibited an architecture with high porosity (85-90%), interconnected pores ∼ 300-400 µm in size, and struts ∼ 3-100 µm in thickness containing 0-80 vol% HA whisker or powder reinforcements. HA reinforcement enabled a compressive modulus of up to ∼ 1 MPa, which was an order of magnitude greater than unreinforced collagen scaffolds. The compressive modulus was also at least one order of magnitude greater than comparable freeze-dried HA-collagen scaffolds and two orders of magnitude greater than absorbable collagen sponges used clinically. Moreover, scaffolds reinforced with up to 60 vol% HA exhibited fully recoverable elastic deformation upon loading to 50% compressive strain for at least 100,000 cycles. Thus, the scaffold mechanical properties were well-suited for surgical handling, fixation, and bearing osteogenic loads during bone regeneration. The scaffold architecture, permeability, and composition were shown to be conducive to the infiltration and differentiation of adipose-derive stromal cells in vitro. Acellular scaffolds were demonstrated to induce angiogenesis and osteogenesis after subcutaneous ectopic implantation by recruiting endogenous cell populations, suggesting that the scaffolds were osteoinductive.

A probabilistic damage model based on direct 3-D correlation of strain to damage formation following fatigue loading of rat femora.

Microdamage accumulates in bone due to repetitive or excessive mechanical loading, and accumulation of damage can lead to an increase in fracture susceptibility. Understanding the stress or strain criterion for damage formation would allow improved predictive modeling to better assess experimental results or evaluate training regimens. Finite element models coupled with three-dimensional measurements of damage were used to directly correlate damage formation to the local strain state in whole rat femora subjected to three-point bending fatigue. Images of accumulated damage from contrast-enhanced micro-CT were overlaid onto the calculated strain result to determine the strain associated with damage. Most microdamage accumulated in areas where the first principal strain exceeded 0.5%, but damage also occurred at lower strains when applied over sufficiently large volumes. As such, a single threshold strain was not a good predictor of damage. In order to capture the apparently stochastic nature of damage formation, a Weibull statistical model was applied. The model provided a good fit to the data, and a fit based on a subset of the data was able to predict the results in the remaining samples with an RMS error of 17%. These results demonstrate that damage formation is dependent on principal strain, but has a random component that is likely due to the presence of pores or flaws smaller than the resolution of the model that act as stress concentrations in bone.

Shear strength and toughness of trabecular bone are more sensitive to density than damage.

Microdamage occurs in trabecular bone under normal loading, which impairs the mechanical properties. Architectural degradation associated with osteoporosis increases damage susceptibility, resulting in a cumulative negative effect on the mechanical properties. Treatments for osteoporosis could be targeted toward increased bone mineral density, improved architecture, or repair and prevention of microdamage. Delineating the relative roles of damage and architectural degradation on trabecular bone strength will provide insight into the most beneficial targets. In this study, damage was induced in bovine trabecular bone samples by axial compression, and the effects on the mechanical properties in shear were assessed. The damaged shear modulus, shear yield stress, ultimate shear stress, and energy to failure all depended on induced damage and decreased as the architecture became more rod-like. The changes in ultimate shear strength and toughness were proportional to the decrease in shear modulus, consistent with an effective decrease in the cross-section of trabeculae based on cellular solid analysis. For typical ranges of bone volume fraction in human bone, the strength and toughness were much more sensitive to decreased volume fraction than to induced mechanical damage. While ultimately repairing or avoiding damage to the bone structure and increasing bone density both improve mechanical properties, increasing bone density is the more important contributor to bone strength.

Detection of fatigue microdamage in whole rat femora using contrast-enhanced micro-computed tomography.

Microdamage in bone tissue is typically studied using destructive, two-dimensional histological techniques. Contrast-enhanced micro-computed tomography (micro-CT) was recently demonstrated to enable non-destructive, three-dimensional (3-D) detection of microdamage in machined cortical and trabecular bone specimens in vitro. However, the accumulation of microdamage in whole bones is influenced by variations in the magnitude and mode of loading due to the complex whole bone morphology. Therefore, the objective of this study was to detect the presence, spatial location, and accumulation of fatigue microdamage in whole rat femora in vitro using micro-CT with a BaSO(4) contrast agent. Microdamage was detected and observed to accumulate at specific spatial locations within the cortex of femora loaded in cyclic three-point bending to a 5% or 10% reduction in secant modulus. The ratio of the segmented BaSO(4) stain volume (SV) to the total volume (TV) of cortical bone was adopted as a measure of damage. The amount of microdamage measured by micro-CT (SV/TV) was significantly greater for both loaded groups compared to the control group (p<0.05), but the difference between loaded groups was not statistically significant. At least one distinct region of microdamage, as indicated by the segmented SV, was observed in 85% of loaded specimens. A specimen-specific finite element model confirmed elevated tensile principal strains localized in regions of tissue corresponding to the accumulated microdamage. These regions were not always located where one might expect a priori based upon Euler-Bernoulli beam theory, demonstrating the utility of contrast-enhanced micro-CT for non-destructive, 3-D detection of fatigue microdamage in whole bones in vitro.