Epithelial Tissue Engineering & Drug Delivery
Improving Drug Transport Through Tight Junctions
(A) SEM of nanostructured patterns at varying diameters and pitch distances. (B) Through TIRF imaging of the basolateral side, nanostructured films are shown to increase the transport of FITC-IgG in nanostructured films in comparison to flat films. (C) Live imaging of tight junctions shows the zigzag and aggregate morphology of tight junction protein ZO-1 in comparison to flat films and non-treated films.
Recent Publications: Huang X, et al. (2019) BioRxiv doi: 10.1101/858118
Point(s) of Contact: Dr. Xiao Huang, Eva Hansen
Microstructure and nanostructure-mediated transport of biologics across epithelial tissue
Corneal blindness affects more than 10 million people worldwide, with corneal transplants being the only currently available treatment. Issues such as donor shortages and immune rejections have motivated attempts to develop tissue-engineered corneal replacements. However, a clinically viable cornea has still not been produced, largely due to the difficulty in recreating the nanostructure of the cornea. The presence of quiescent cells, called keratocytes, that exist within aligned 30 nm collagen fibrils in the corneal matrix, has been considered crucial to mechanical strength and transparency—the two main functions of the cornea. Here, we are focusing on how environmental cues such as matrix stiffness and topography regulate corneal cell phenotype and matrix synthesis, thereby influencing corneal wound healing responses and the successful design of a tissue engineered cornea.
Microneedle patches covered with nanotopography enhance epithelial permeability.
Planar microdevices deliver drug to ocular epithelium and increase paracellular transport by disrupting the connections between epithelial cells.
In collaboration with Kimberly Clark.
Matrix nanotopography and keloid proliferation: implications for dermal scar healing
Keloids are benign dermal tumors characterized by excessive deposition of extracellular matrix. The lesions cause pain, disfigurement, and impaired mobility. Although treatment strategies include surgical excision and intralesional corticosteroid injections, an effective regimen is yet to be established due to high rates of recurrence.
In our lab, we have shown that topographical cues in the matrix reduce scar formation and fibrosis in different types of tissue such as cardiac and corneal tissue. We are investigating if these studies translate to keloid scar healing as well. Our results will have significant implications for the development of biocompatible dermal patches with defined collagen nanotopography to inhibit keloid growth and aid in the design of an effective therapy for keloid management.
Collagen fibrils are aligned on surfaces influencing the behavior of cell growth on those surfaces.
In collaboration with Fibralign.
Artificial scaffolds for directing 3D self-assembly of epithelial tissues
Reconstructing organs in vitro requires understanding how cells self-organize in the context of other cells and their supporting 3D scaffold. We tune the physicochemical properties of different biomimetic materials in order to control the position and polarity of epithelial cells. Our goal is to study human biology in 3D by reassembling functional epithelial glands in vitro.
Changing the scaffold material surrounding two different cell types can alter the organization of the cells so that either of the two cell types may surround the other.
Cells self-assemble around a PEG micro-rod scaffold.
In collaboration with the Gartner Lab.