This NIH/NIBIB supported research seeks to develop polymer biomaterials that prevent bacterial colonization and subsequent biofilm formation by using novel small molecules that do not kill bacteria but rather negate biofilm formation. Biomaterials will release a variety of novel "anti-biofilm" therapies rather than employing a toxic compound such as an anti-biotic or disinfectant. Such therapies include: gallium-siderophore complexes that interfere with iron metabolism, DNAse enzymes that disrupt the biofilm exopolymer matrix, specific species adhesion blockers, d-amino acid based small peptides that block bacterial amyloid formation.
Engineering Infection Immunity
This group of NIH funded research projects seeks to generate biomaterials that self-vaccinate the host in order to prevent medical device based infections. Biomaterial scaffolds will be created that can control dendritic cell (DCs) activation and efficiently transfect DCs with either pDNA or mRNA nucleic acid vaccines.
Tissue Regeneration/Replacement by Exosome Engineering
Can certain macrophage phenotypes continue to differentiate in desired tissue cells, exhibiting stem-cell like behavior? If so, can biomaterials be designed to engineer macrophage phenotype and affect such plasticity?
Growing evidence suggests that transcriptional regulators and miRNA molecules encapsulated within membrane vesicles (i.e., exosomes, microvesicles) that are released by the parent cell can modify the phenotype of target cells. Membrane vesicles represent a mechanism of intercellular communication that is conserved evolutionarily and involves the transfer of molecules able to induce epigenetic changes in recipient cells. Extracellular vesicles (EVs) can present on their surfaces host membrane cell markers and EVs can internally carry proteins (e.g., transcription factors), bioactive lipids, and nucleic acids (mRNAs, miRNAs). Somatic cells can be reprogrammed to reach an embryonic stem cell-like state by overexpression of certain factors, such as miRNAs. This particulate communication can also be bidirectional, tissue-injured cells may induce gene expression and differentiation decisions in progenitor cells. Conversely, stem cell-derived vesicles may reprogram somatic cells into progenitor cells subsequently activating regenerative mechanisms.
We are developing biomaterial platform technologies to engineer specific EVs, thus impacting tissue repair, regeneration, and organ transplantation.