Cytoprotection: Immune and Matrix Modulation of Tissue Repair
Annual rept. 15 Mar 2010-14 Mar 2011
BENAROYA RESEARCH INST SEATTLE WA
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The research program consists of a set of projects addressing two Aims1 to develop and evaluate formulations of natural cytokines, ligands, and extracellular matrix ECM components to promote regulatory T-cell Treg and macrophage persistence and function, further to control inflammation and improve healing, and 2 to incorporate promising strategies from Aim 1 into a therapeutic device the Cytoprotective Implant, or CI and test it in an engineered replacement for skeletal muscle the myobridge, also under development in this program. Toward these objectives, significant progress has been made in the following major areas 1 Novel hyaluronan HA ECM hydrogels have been produced that incorporate a number of molecular species to provide potent signals for induction of Treg persistence and function 2 Small interfering siRNAs introduced into na ve human CD4 T-cells were shown to inhibit expression of target genes predicted to affect the generation or stability of Tregs, or inflammatory Th17 T-cells 3 Beta-2 integrins were implicated as inhibitors of pro-inflammatory responses in a variety of macrophage populations 4 Inflammatory cytokine blockade with an interleukin 1-receptor antagonist was shown to blunt inflammatory responses in humans 5 Supportive ECM scaffolds for the CI were evaluated and a novel approach for local, controlled-release of anti-inflammatory HA was developed and 6 Design and fabrication processes for the myobridge test-bed have been substantially refined.
- Medicine and Medical Research
- Organic Chemistry