Performance-Driven Tissue Engineering Templates, 01-9551

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Principal Investigators
Neal K. Vail
Daniel Nicolella
Kwai Chan
Heather Hanson
W. Royall Cox
Richard Suzuki
David Carnes, UTHSC-SA (Consultant)

Inclusive Dates:  07/01/ 05 – Current

Background - Tissue engineering is the science of persuading living systems to regenerate or repair tissues that fail to heal spontaneously. In one approach, a template that supports and guides the generation of new tissue is implanted into a living system to facilitate tissue repair. Tissue engineering templates use a combination of engineering design and material selection to create performance-driven components that guide the generation of new tissue. Implicit in tissue engineering is the need to generate vasculature (angiogenesis) to support the nutritional and waste-removal requirements of regenerating tissue. Angiogenesis and tissue regeneration are intimately linked, and efforts to guide the regeneration of specific tissue must be cognizant of factors that initiate and support a functional microvasculature system during new tissue development.

Approach - Our goal is to combine biological requirements with engineering design and materials to create performance-driven tissue-engineering templates that support the generation of new functional bone tissue. The governing program hypothesis is that tissue-engineering template architectural design dictates both the character and extent of the bone-healing response. Our approach will be to determine macroscale template design parameters that facilitate angiogenesis, as well as the cascade of local events at the wound site that lead to restoration of functional bone tissue. We will establish the influence of specific macroporous geometries on fibrin clot formation, microvascular cell ingrowth, and osseous tissue formation with a combination of in vitro and in vivo studies using specifically engineered templates. These design parameters will then be used in a biomechanical model to predict optimal porous structure architectures to support the mechanical requirements of bone healing. We are developing new materials formulations from which to fabricate our templates. We are developing a multiscale modeling approach to predict material properties, corroborating these results with experiment, and using the results as input to our biomechanical models. The project integrates advanced engineering micromechanical experimental and analytical techniques with cell and molecular biology to achieve a better understanding of bone cell function with the overall goal of producing optimized tissue engineering templates. The project is categorized into three major subprojects, including (1) design and implementation of template fabrication platform, (2) materials development and modeling, and (3) template design, optimization, and evaluation.

Accomplishments - Although the project has only recently been funded, significant progress has been made in all three subprojects. Our initial materials system consists of a nanosized hydroxyapatite formulated into a high-solids ink. We have demonstrated the synthesis of phase pure hydroxyapatite nanoparticles with a particle size of 200 to 300 nanometers and produced inks with a solids loading of 50 wt%. We have also demonstrated the synthesis of other nanosized calcium phosphates, both amorphous and crystalline. We have completed the design and specification of the template fabrication platform and are currently in the process of assembly. We are initiating in vitro/in vivo studies to determine template architecture parameters.

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