Our Research Programs
Microbiome-mediated immunoengineering
Although bacteria are commonly perceived as infection-causing pathogens, we know that commensal bacteria play an essential role in preserving human health. We are among the first to study how to leverage the local microbiome to promote scarless healing in a child’s airway. We propose the novel concept of engineering the immune response to injury by modulating the airway microbiome.
Through multi-omics of samples from children affected by subglottic stenosis, the disregulated scarring of the trachea, we aim to understand the crosstalk between the microbiome and the immune system, which we then confirm leveraging multiple animal models. To translate this approach to the clinic, we are developing innovative delivery tools for antimicrobial peptides and antibiotics to modulate the local microbiome to control the immune response to injury and ultimately achieve scarless healing.
Overall, we are extremely excited by the opportunity to guide regenerative repair by harnessing the immune system through the new tool of microbiome modulation.
Endotracheal tube coated with a PLGA-Antimicrobial Peptide (AMP) coating for the localized modulation of the airway microbiome. While bacteria (SEM false coloring) grow on regular and PLGA coated endotracheal tubes, when a broad spectrum antimicrobial peptide is incorporated, the bacterial presence is significantly changed.
Stem cells populating a scaffold
Tissue engineering: throat, ear, nose and knees
There is a lot of engineered cartilage developed in labs around the world, but very little finds its way to the patients. We have adopted a fast translation approach to reach the clinic in the next 3 years. Our priority target is engineering cartilage for laryngotracheal reconstruction to enable infants and children with subglottic stenosis to breathe again without a tracheostomy. For rapid translation, we design scaffolds based on FDA approved materials: starting from the simplest building blocks we build the complexity that drives stem cell differentiation. Moreover, the engineered tissues we develop are based on new stem cell sources that can be harvested with minimally invasive outpatient procedures. Once translated to the clinic, our approach will then be applied to repair knees (focal lesions and osteoarthritis), nose (trauma), and ear (microtia).
To learn how to build cartilage, we also study how the embryo does it and how we can mimic it effectively in the lab with synthetic materials. All of our work on tissue engineering is driven by a deeper understanding of the underlying mechanism of developmental and stem cell biology, learning how to maintain cell stemness during expansion and how to rapidly drive chondrogenesis once on a scaffold.
drug delivery for voice restoration
Vocal fold scarring is a significant cause of speech impairment and negatively impacts psychosocial development in children as well as everyday life in adults, particularly for those whose work heavily relies on voice. Vocal fold scarring is the result of fibroblasts differentiating to contractile myofibroblasts which excessively secrete extracellular matrix. Current therapies are limited to local steroid injections, but they have low clinical efficacy, rapid drug clearance, and poor regenerative capacity. Inspired by the matrix remodeling processes occurring during tissue development, we have identified potential targets to regulate human vocal fold myofibroblast differentiation and function. To prevent and most importantly reverse vocal fold scarring, we are deploying an array of drug delivery approaches, including biodegradable microspheres, injectable microgels, and lipid nanoparticles.
Biodegredable microspheres for controlled delivery
Histology of a rat airway showing the cartilage tracheal rings, cricoid, and larynx (dark blue) and the vocal folds (light blue, interior from the larynx)
Organ-on-chip and bioreactors
We are leaders in the development of joint-on-a-chip technologies to model the osteochondral junction and the crosstalk occurring during disease. We have been pushing 3D printing to generate novel bioreactor and scaffolds fit for medium to high throughput screening of candidate disease modifying drugs.
We are now developing new mechanically activated joint bioreactors and in vitro models of the airway.