Visiting Scholar Presentation: Advanced in vitro three-dimensional cornea tissue model

The reinvention of structural biopolymers as technical materials has enabled the use of natural polymers in applications that include drug delivery, regenerative medicine, biosensing and optoelectronics. In this context, the advanced nanomanufacturing of structural proteins – such as collagen and silk – in complex three-dimensional architectures organized across several scales ranging from nano to macro has served the purpose of engineering unprecedented materials that can bridge the biotic/abiotic interface. In particular, the fabrication of living materials that combine tissue-like environments with multi cellular populations provides technological tools that can be used for tissue regeneration, drug screening and to study tissue-pathogen interactions. In this context, the in vitro design of tissues that are germane to the eye represents a key step to engineer the biotic/abiotic interface in humans.  The need for human corneal tissue as replacements grafts (keratoplasty) and for research/screening tools, continues to expand, with few new options available to meet these needs. New tissue-engineered human cornea systems are essential for both human ocular disease management as well as expanded screening tools. Our hypothesis is that tissue engineered cornea systems with appropriate mechanics, cultivation conditions and innervation, will provide functional human cornea tissue equivalents to meet such in vitro and in vivo needs. Toward this goal, we have established an in vitro cornea tissue model based on engineered silk film substrates and we have investigated the interplay of human corneal stromal stem cells, human corneal epithelial cells, and innervation. In this in vitro tissue model, we were able to recapitulate the physiological organization and phenotype of the stromal cells, the multi-layer functional features of the epithelial cells, sustained cultivation for chronic studies, and the native density and organization of nerve endings. Furthermore, the current model has been shown to be responsive to several known ocular irritants, as by pain mediators quantification and cellular recovery upon stimulation. This work should propel these new advanced in vitro, human, cornea tissue equivalents to the forefront of in vitro tissue systems to simulate human-related outcomes, including acute and chronic functions in healthy and diseased corneal states.

Chiara E. Ghezzi  - BIO

Chiara

Dr. Ghezzi is assistant professor in the department of Biomedical Engineering at University of Massachusetts Lowell. She received her undergraduate and master’s degrees in biomedical engineering from Politecnico di Milano, in Italy. During her doctoral studies at McGill University in Materials Engineering, she developed several fabrication strategies based on natural polymers, such as collagen and silk, to study cellular functions in soft materials.  Dr. Ghezzi has a strong engineering background, with specific training and expertise in biomedical and material science. Her research interests have been centered in developing biopolymer substrates to mimic physiological native environments towards medical devices and functional tissue models, with particular emphasis on cornea and other soft tissues. Her research focus is on biopolymer engineering to understand structure-function relationships, with emphasis on studies related to biomaterials design, drug delivery, and material host responses. Before joining UML, she was a Research Assistant Professor in the BME Department at Tufts University and the Scientific Coordinator for the NIH P41 Tissue Engineering Resource Center (TERC) between the groups of David Kaplan at Tufts University and Gordana Vunjak-Novakovic at Columbia University.