Cross-linked hydrogels for the delivery of growth factors in tissue engineering

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Cross-linked hydrogels for the delivery of growth factors in tissue engineering

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Title: Cross-linked hydrogels for the delivery of growth factors in tissue engineering
Author: Brown, Chad David
Abstract: The goal of tissue engineering is the regeneration or replacement of failed or damaged tissues with viable and functional tissues that integrate with the host system. However, this vision has not yet been fully realized. One difficulty in producing large tissue substitutes is maintaining the viability of cells on or within polymer scaffolds. Many factors, several associated with undesirable wound healing, may lead to the demise of cells contained within a tissue-engineering scaffold. These factors include difficulty in the delivery of nutrients or removal of waste products, attack of implanted cells by the host immune system, or a lack of proper cell proliferation and differentiation. The recent increase in the number of available recombinant proteins, including growth factors has allowed for the manipulation of cell function and differentiation. However, the success of these important biomolecules is dependent on the amount delivered to the cell and the timing of their delivery. Important processes such as inflammation, wound healing and associated angiogenesis, immune regulation, and cellular differentiation and proliferation may be mediated when these factors are delivered in an appropriate manner. Many traditional tissue-engineering scaffolds, such as poly(lactide-co-glycolide), are relatively hydrophobic in nature and require processing conditions that can denature proteins. Further, protein delivery systems fabricated from these polymers result in non-uniform protein distribution and lead to non-ideal release characteristics. Hydrogels provide a more stable environment for proteins; however, they swell rapidly and release entrapped biomolecules quickly. It is hypothesized that proteins can be delivered in a controlled and stable manner by combining appropriate ratios of hydrophobic and hydrophilic polymers in cross-linked networks, thus promoting beneficial biological functions. In this work, synthetic and natural polymers were utilized to develop physically or chemically cross-linked protein delivery systems capable of stable and controlled delivery of growth factors with appropriate individual release kinetics in an effort to promote proper wound healing events such as angiogenesis.
Description: Thesis (Ph. D.)--University of Washington, 2003
URI: http://hdl.handle.net/1773/8102

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