Growth factors are recognized as a vital component in the biological repair process, and the strategies developed for in situ tissue engineering and regenerative medicine require localized delivery of growth factors to facilitate wound healing. The primary motivation of this work is to develop localizable cell-based growth factor delivery systems for such strategies. Using encapsulated cell technologies and genetic engineering, this thesis focuses on the development of three methods for the delivery of insulin-like growth factor (IGF-I), a potent mitogen and differentiation factor with particular relevance to orthopedic tissue wound healing. The first system utilizes encapsulated genetically modified allogeneic cells to synthesize and delivery bioactive IGF-I in a continuous manner. As demonstrated over the course of 10 days in vitro, release is constitutive, predictable, and exhibits highly repeatable first-order kinetics with no initial burst. The second system consists of an encapsulated genetically engineered xenogeneic cell line that is capable of doxycycline induced IGF-I gene expression, with control of the timing and dosage of IGF-I delivery being demonstrated over the course of 10 days in vitro. To further explore the utility of regulated cell-based delivery for IGF-I in situ, a method for controlling encapsulated cellular response within an implantation site has been developed using a combined cell-based and polymeric-based approach. Doxycycline loaded PLGA microspheres have been combined with encapsulated cells capable of doxycycline-regulated IGF-I synthesis and delivery to demonstrate the utility of the polymer spheres as a method for modulating cell-based delivery in situ.
Patel, Roshni S.,
"Cell-based Growth Factor Delivery For In Situ Tissue Regeneration and Repair"
(2011).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z02F7KPT
