Performance-Driven Tissue Engineering Templates, 01-R9551

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

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 broken down into three major sub-projects: (1) design and implementation of template fabrication platform, (2) materials development and modeling, and (3) template design, optimization and evaluation.

Accomplishments - This program is in its second year. During the last year, we made significant progress in all three subprojects. The template fabrication platform is complete and is undergoing shakedown. The platform consists of a high-precision dispensing system for the selective deposition of materials ranging from high-solids pastes to viscous polymer solutions. Positioning is provided by a high-resolution, three-axis system that is mounted on an isolation table to minimize vibrations. The system currently has a positional resolution of 0.1 micrometer and deposition resolution of 25 micrometers. The entire fabrication system is controlled by a custom software interface that provides for graphical rendering of three-dimensional objects, segmentation of solid objects into machine instructions, and control of the hardware for fabrication of objects. Materials development has focused on the synthesis of starting materials and the formulation of fluids for deposition. Of primary interest has been hydroxyapatite-based pastes with specific properties to accommodate the deposition process, such as particle size, viscosity, and elastic modulus. We have demonstrated the deposition of these paste formulations and are working on additional material formulations to address other functional material applications. The materials developed thus far are being characterized for key properties necessary for developing material models to support the optimization of biomechanical performance of fabricated scaffolds. Considerable work has been done on developing in vitro methods to study and identify key parameters affecting the biological performance of tissue engineering scaffolds. Results thus far obtained in this project are being incorporated into abstracts for submission to upcoming conferences, such as Society for Biomaterials. Additionally, two NIH proposal efforts are in development using the results of this program. Several invention disclosures are being finalized.

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