Platelets are megakaryocyte-derived enucleated blood cells that are primarily responsible for hemostasis (staunching bleeding) in the body. Platelets render hemostasis by marginating across bulk blood flow towards the vascular injury site, adhering to the site via molecular interactions with specific proteins (e.g. vWF and collagen), undergoing activation as an effect of adhesion-induced signaling, secreting platelet agonists (e.g. ADP and thrombin) to further locally activate other platelets and promoting aggregation of these activated platelets via inter-platelet bridging mediated by ligand interactions with platelet surface integrins and selectins.
Dysregulated hemostatic mechanisms often lead to hyperaggregation of activated platelets and overaction of coagulation events, ultimately leading to occlusive clot formation. Such occlusive clotting is a primary characteristic in many vascular disease conditions, leading to ischemia, unstable angina, myocardial infarction, stroke etc. Such conditions lead to significant tissue morbidity and mortality, and hence dissolving or removing the clot rapidly to re-establish blood flow to critical tissues and organs remains a clinical mainstay in treating these conditions. The mechanical strategies for clot removal include thrombectomy or angioplasty (with or without stenting) which are invasive and can cause secondary injuries and thrombotic events, leading to re-occlusion.
Disseminated metastatic cells that intravasate into circulation (called circulating tumor cells or CTCs) are expected to have poor survival rates due to lack of matrix adhesion, increased fluid mechanical stresses of blood circulation and action of immune cells. Yet, some of these cells are found to effectively avoid anoikis, undergo epithelial-to-mesenchymal transformation en route to intravasation, avoid immune surveillance in circulation and undergo arrest or adhesion at distal site vasculature to form metastatic colonies.
Interaction of biomedical devices and implants with the living tissue is largely mediated by surface chemistry and surface morphology. For example, for blood-contacting devices (vascular grafts, wound healing systems, dialysis membranes etc.), protein adhesion, denaturation and retention on the device surface dictates the long term favorable or unfavorable cellular interactions with the device. For bio-inspired devices or tissue engineered constructs, often specific cell-material interactions are required for intended property and functions. To this end, our laboratory develops and studies variety of physical and chemical surface modification technologies for preventing or promoting specific protein-material and cell-material interactions.
Photodynamic Therapy (PDT) is a promising cancer treatment strategy that can potentially reduce the risks of systemic toxicity, collateral healthy tissue damage and surgical trauma and tissue debilitation, especially when repeated treatment becomes necessary because of the aggressive nature of the cancer. PDT involves three components: a photosensitizer (PS) drug, a specific wavelength of drug-activating light and oxygen. Light activation of a photosensitizer results in energy transfer cascades that ultimately yield cytotoxic reactive oxygen species, which can then render apoptotic and necrotic cell death.