Nanofibrous materials have become an important component in the field of regenerative medicine. Due to their resemblance with extracellular matrix proteins, nanofibrous materials are capable of eliciting natural cell behaviors. One class of self-assembling molecules that forms nanofibers is peptide amphiphiles (PAs). The modularity of self-assembly affords the ability to tailor PA assemblies for specific applications through molecular design and mixing of different components. Illustrated here is an extended-micelle-forming PA synthesized in a branched architecture composed of histidine and serine amino acids conjugated to a palmitoyl tail. Using histidine residues as molecular switches, PA solutions are capable of transitioning from viscoelastic liquids in mildly acidic conditions to selfsupporting hydrogels above pH 6.5. By modulating the concentration of the PAs, biocompatible hydrogels of 0.2-10 kPa were achieved. This PA hydrogel system is a potential candidate as an injectable three-dimensional tissue scaffold.
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.
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