Developing Multi-biofunctional Polymeric Materials
The BMDiLab aims to develop biointeractive multi-functional biomaterials using conjugation, polymer surface and bulk modification, biologically active hydrogel development, and controlled release for discovery in biological systems and for the development of novel approaches to mediate processes at the cellular and sub-cellular levels.
Liposomes are highly effective at entrapping, protecting, delivering, and enhancing the pharmacokinetic properties of a wide variety of drug cargo including those with limited therapeutic windows. Moreover, the encapsulation of therapeutics in liposomes can address their utility challenges including high reactivity and limited control of delivery to enhance clinical translation. Overall, we aim to develop liposomal constructs undergirded with high cell specificity and triggered cargo release to dramatically improve aspects of targeted drug delivery including protection from off-target reactivity and precision delivery for translation into clinical practice.
Keywords: Nanoparticles, lipid-based constructs, targeted drug delivery, therapeutics
1. Surface Modification of Artificial Lung Circuit Materials
While artificial lungs are capable of removing carbon dioxide from blood and oxygenating tissue in lung disease patients, the interaction of their circuit materials and flowing blood is complex. The total surface area of a circuit is large, and their gas exchange membranes make up the majority. They get fouled with blood clotting proteins which leads to clots growing on circuit materials, diminishing gas exchange efficiency, and occluding blood vessels to limit tissue perfusion. When systemic-acting anticoagulants are administered, clotting is reduced in these devices but however expose patients to risks of bleeding complications. In this project, the BMDilab and its collaborators are investigating surface modification approaches for artificial lung circuits to eliminate their fouling by surface grafting of polymers including zwitterionic materials.
Keywords: Respiratory support, artificial lungs, surface modification, anti-fouling surfaces, and zwitterionic grafting.
2. Device-Related Infections
Replacing a weight-bearing joint is accompanied by long procedures, longer recovery times with intensive monitoring, and prolonged recovery times if the surgical site becomes infected. Without prophylactic antibacterial properties incorporated into knee replacements, revision surgery is usually the only corrective option after infection. The objective of this research is to develop antibacterial prophylactic inserts as integrating or adjunctive ad-on to knee replacement prosthesis. Here, we are using 3D printing for prototyping, custom petri dishes for evaluating adhesion and LIVE/DEAD staining assays to study the killing biofilm-protected bacteria as a function of nitric oxide release.
Keywords: implant-device related infections, total knee replacement prosthesis, self-sterilizing prophylactic inserts, and minimizing revision surgeries.
3. Bacterial Adhesion and Biofilm
The need for implantable devices for the treatment and support of patients is ever increasing, yet their interactions with the host often lead to complications that increase morbidity and in some cases mortality. In their interaction with the host, they can activate the blood into clots and result in embolic complications in the brain, lungs, heart, and peripheries. We see these manifest as stroke, heart attack, deep vein thrombosis, etc. Furthermore because we don’t live in a sterile world, these devices get contaminated during implantation even against best sterile protocols in the operating room and expose the patient to the risk of infections. The objective of this research is to attain self-sterilizing biomaterial surfaces by controlling bacteria adhesion and biofilm formation with surface release of therapeutic (bactericidal and cyto-compatible) levels of anti-bacterial agents including nitric oxide.
Keywords: anti-adhesion, biofilm dispersal, methicillin resistant staphylococcus aureus (MRSA), methicillin resistant staphylococcus epidermidis (MRSE), bactericidal surface activity, nitric oxide, controlled release.
Keywords: shingles, nociception, pain relief, biomaterial scaffolding, bioactive matrices, cell-to-cell release tunability.
4. Multi-biofunctional Polymer Platforms
Herpes Zoster (Shingles) disease is a painful rash caused by the varicella zoster virus. The virus typically infects children, teen, and young adults; and manifests as chickenpox. After treatment the virus is not eradicated but remains dormant until it is reactivated in adults due compromised immune system, age, stress, and effects of immunosuppressive drugs or a combination of these conditions. The result is an acute and chronic bodily burning sensation described by some patients as a feeling of lava poured onto the skin. Other effects include decreased general and mental health and high toll on emotional, social, and physical health. The objective of this research is to develop a drug-releasing BioPatch to modulate pain perception, aid wound healing, and potentially anti-viral effects. We are using custom biomaterial scaffolding for tunable matrix organization of bioactive cells. The ability to easily remodel the scaffolding biomaterial allows for a highly controlled drug release profiles.
5. Tools for Biointerfaces Research
The effect of surface coatings on the performance of anti-fouling activity under flow can be influenced by the flow/coating interactions. For long-term anti-biofouling applications involving complex media flow, the blood-contacting surface not only have to inhibit fouling from whole blood, a challenging task, but also do so while under hemodynamic stress perturbations for the entire desired duration of the application. Therefore these coatings must present effective steric repulsion of nonspecific protein adsorption or have an appropriate surface packing density to form a hydration film barrier between the substrate and complex media. An equally important factor is that the coating must remain immobilized to the surface and not erode or leach due to detachment of linkers or anchoring mechanism that keep the coating tethered to the substrate. The objective of this research is to study the antifouling activity surfaces as a function coating and coating properties.
Keywords: biofouling, anti-fouling coatings, stability of coating during flow, thrombosis/blood coagulation. .