Three-dimensional (3D) Alzheimer’s disease (AD) model
Alzheimer’s disease is a very common neurodegenerative disease with very few therapy options. This is partially because the mechanism of Alzheimer’s disease is poorly understood. We aim to create a new system to model Alzheimer’s disease by studying how mechanical stiffness of the extracellular matrix is related to the known biochemical cues related to this disease.
Thus, we utilize cerebral organoids (COs) formed from human induced pluripotent stem cells (hiPSC) lines derived from AD and healthy control (HC) donors. We culture the COs within a hybrid synthetic polymer/natural tissue-based three-dimensional (3D) model with tunable mechanical stiffness. This new system enable us to systematically evaluate the contribution of ECM biomechanical properties to the development of AD neuropathology.
Biomimetic multi-factor delivery system
The repair phases of human diseases consist of closely interconnected events. We are developing new treatment methodologies, which consider these interrelated phases and support these processes in their endogenously-occurring order, which is an unmet clinical need
Retinal ganglion cell axon regeneration
Traumatic optic neuropathy is the sudden death of retinal ganglion cells (RGC) that leads to vision loss. This optic neuropathy causes the obstruction of axonal transport of neurotrophic factors (NTFs), due to which many treatment methodologies focus on NTFs delivery into the vitreous humor. However, optic neuropathies also cause neurodegeneration by the accompanying neurotoxicity.
In this contect, we are developing a new system that can effectively address neurotoxicity while continuously supporting NTFs to increase RGC survival and axon regeneration after the traumatic optic neuropathy. To achieve this, we utilize a nanoparticles (NPs) system, co-delivering NTFs and an anti-neurotoxic agent. We fabricate NPs using a sulfonated random copolymer (S-PSHU): sulfonated poly(serinol hexamethylene urea). The negatively charged sulfonate group mimics the biofunction of natural heparin, interacting with NTFs. Thus, this system is designed to 1) deliver both NTFs and an anti-neurotoxic agent, 2) diminish neurotoxicity in an early stage of disease by faster release of anti-neurotoxic agent than NTFs, 3) sustain NTFs delivery by the interactions between sulfonate groups and NTFs while preserving their bioactivity, ensuring prolonged survival of RGC and promoting axon regeneration.
Cardiac protection from myocardial infarction
Acute myocardial infarction (MI), a dramatically increased ischemic cardiac disease in recent years, is regional damage (or death) of heart muscle tissues due to oxygen shortages and cardiac cell apoptosis. MI is a multifactorial event comprising different repair phases such as the inflammatory phase, the proliferative phase and the maturation phase. During the inflammatory phase, pro-inflammatory cytokines are overexpressed and significant number of cardiomyocytes (CMs) die. Subsequently, neovessels are formed during the proliferative phase and further matured during the maturation phase. Although the post-MI cardiac repair has been competitively studied, very few (or none) strategies have been developed that simultaneously target the healing processes during three post-MI repair phases: anti-inflammation, CM proliferation, angiogenesis and vascular maturation.
To address it, we develop an injectable one-pot system that co-delivers four therapeutic agents: 1) anti-inflammatory agent, 2) CM proliferative agent, 3) angiogenic agent and 4) vascular maturation agent. We deliver four agents using SRTG, a custom-designed poly(N-isopropylacrylamide) (PNIPAAm)-co-sulfonated poly(serinol hexamethylene urea) (PSHU), and a sulfonated PSHU NPs. The system is designed to achieve three groups of phased release properties thatcorrespond to three post-MI cardiac repair phases. Thus, it delivers each agent for desired periods that correspond to endogenously-occurring post-MI repair phase, which would be clinically more relevant than a system delivering multiple therapeutic agents in a non-phased and uncontrolled manner.
Antimicrobial surgical drape
A surgical site infection (SSI) is defined as an infection that is developed during a surgical procedure or up to 30 days after. In the US, 2-5% of patients undergoing surgery suffer from SSIs. These patients have 2-11 times higher risk of death. During the surgery, one of the main sources for pathogens is often thought to be the skin surface. Skin antiseptic preparations along with antiseptic-impregnated surgical incision drapes (SIDs) are used as a barrier to prevent re-colonization and immobilize the organisms that might have survived the treatment. However, these drapes present numerous pitfalls. Amongst the most severe are that the placement process of the drapes is time consuming, they often do not remain well-attached and they only provide temporary protection. Similarly, there are risks associated with epidermal cell layer detachment during removal, exposing bacteria found beneath the skin, thereby increasing risk of secondary bacterial infection.
In order to overcome the limitations associated with SIDs, we develop a quaternized polymer-based sprayable antimicrobial surgical coating that can act as a SID. This polymer is specifically designed to be sprayed onto the skin, turns into a thin coating, and can be removed by alcohol (e.g., isoproopanol) washing.