Abstract
One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.
Highlights
Significant progress has been made in the development of engineered tissues for clinical applications including wound and burn repair
Transfer molds were used to cast silk fibroin trenched layers, which were bonded to flat silk films to form closed microchannel networks
Beyond the inherent properties and benefits of silk as a scaffolding material, this work has demonstrated that microfluidics-based construction of microvascular networks from lithographically fabricated master molds will enable the formation of an integrated microvasculature for tissue engineering applications
Summary
Significant progress has been made in the development of engineered tissues for clinical applications including wound and burn repair. Progress towards engineering complex tissues and organs has been limited by challenges in forming an integrated and functional vasculature. Insufficient vascularization can lead to improper cell integration or cell death in engineered tissue constructs. While endogenous blood vessels can invade the implanted tissue enabling spontaneous blood vessel formation, the rate of neovascularization for millimeter-sized implants typically takes several weeks, such that clinically useful implants would not re-vascularize in a clinically-relevant timeframe [2]. Achieving a replacement tissue with a patent and sustainable microvasculature represents a key, rate limiting step in the formation of most replacement tissues or organ systems
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