Browsing by Author "Hartgerink, Jeffrey D"

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    MultiDomain Peptide Hydrogel for Soft Tissue Regeneration
    (2020-04-24) Moringo, Nicole Christine; Hartgerink, Jeffrey D
    MultiDomain Peptides (MDP) have been designed and synthesized to create biomaterials. MDPs are designed to supramolecularly self-assemble into a nanofibrous hydrogel mimicking the native extracellular matrix. The MDP hydrogel supports cell growth and proliferation in vitro. In vivo the MDP hydrogel elicits a mild inflammatory response resulting in cellular infiltration and vascularization. The goals of this work were to 1) create bioactive MDPs capable of driving biological responses and 2) utilize the MDP hydrogel for soft tissue regeneration. Chapter 1 introduces tissue engineering and explains benefits of utilizing hydrogels for regeneration. Chapter 2 aims to design, synthesize, and characterize bioactive MDP hydrogels. Covalent attachment of growth factor mimics displays bioactive signals creating a scaffold that supports cell growth, proliferation, and differentiation in vitro, in contrast to a non- bioactive MDP. In vivo both MDPs are capable of driving tissue regeneration with undiscernible differences. Thus, the non-bioactive MDP was utilized for the remainder of the thesis. Chapter 3 utilizes the MDP hydrogel to drive tissue regeneration. When applied to full-thickness dermal wounds in diabetic mice, the MDP hydrogel resulted in significantly accelerated wound closure, formation of thick granulation tissue including dense vascularization, innervation, and hair follicle regeneration suggesting the MDP hydrogel could be suitable for treatment of wounds in diabetic patients. Chapter 4 examines the antibacterial of the MDP hydrogel. In vitro the MDP hydrogel inhibits the growth of bacteria; however, however, inhibition of bacterial growth did not occur in infected diabetic wounds. Antibiotics were loaded in the MDP hydrogel to create sustained delivery and increase antibacterial activity. In vitro results revealed potent antibacterial activity; however, bacterial growth was not inhibited in vivo. Chapter 5 investigates the response to the MDP following intramuscular injections. Skeletal muscle regeneration is impeded in volumetric muscle loss due to lack of crucial cells, blood vessels, and nerves. Intramuscular injections of MDP hydrogel are rapidly infiltrated by cells, blood vessels, and neural fascicles suggesting utility of the MDP hydrogel for skeletal muscle regeneration. Lastly, Chapter 6 reiterates the major findings of this work and details future directions and potential for MDP hydrogels as biomaterials for tissue engineering.