Research led by Florida A&M University Pharmaceutics Professor Mandip Sachdeva has resulted in the creation of the first high throughput printing of human cells in a 3D print of the cornea in the U.S.
Florida A&M University Professor of Pharmacy Mandip Sachdeva, center, has worked with his students Paul Dinh, left, an undergraduate studying biology and Shallu Kutlehria, a PhD student studying pharmaceutics, to create the first 3D printed human cornea in the United States. The cornea is made using the Cellink Bio X bio printing machine. (Photo courtesy Tori Schneider/Tallahassee Democrat)
The scientific breakthrough — created in two research laboratories in the Dyson Pharmacy Building on campus — could lead to far-reaching advancements in the medical field, from transplants to testing of new cornea-relief products to cornea wound treatment.
Sachdeva, along with Shallu Kutlehria, a graduate assistant in the College of Pharmacy and Pharmaceutical Sciences, and research assistant Paul Dinh, are completing a white paper to be submitted later this month for journal publication.
The cornea advancement is an outgrowth of research Sachdeva has been engaged in with the help of a grant in 2017 from the National Science Foundation to Florida A&M and the FAMU-FSU College of Engineering.
The grant was awarded to Sachdeva and two FAMU-FSU College of Engineering professors to assist in advanced research in applications for bio printing, aerospace materials and energy.
The Centers of Research Excellence in Science and Technology grant is distributed over five years.
The focus for Sachdeva — who has taught at FAMU for 26 years and been awarded $25 million in research funding over the years — was in developing materials/devices for biological applications, such as a 3D-printed tumor bio system on a chip.
“I was also doing ocular research,” Sachdeva said from his Dyson office. He was aware that scientists at Newcastle University in the U.K. were the first last year with a paper printed in journals on their 3D print of human corneas.
“Essentially, the idea was, ‘Can we do something better than this? Can we simulate the human eye, and put a cornea with cells in it? ‘"
The effort started about a year and a half ago.
In the area of cornea research, his team is printing a cornea which contains the stromal keratocytes in a collagen matrix, which is the case in real cornea.
Though one application could be cornea transplant, other applications include developing an in-vitro diffusion model to ascertain the permeation of drugs and formulations for screening in research.
The team also is developing a blinking eye model, which will be a further improvement in the in vitro model. A prototype has been created.
Sachdeva led a visitor to a basement lab where a replica of a human eye is displayed.
Paul Dinh, a Florida A&M University biology major, sets up the Cellink Bio X bio printer in preparation for creating a 3D printed human cornea in the Dyson Pharmacy building on FAMU's campus Tuesday, June 4, 2019. (Photo courtesy Tori Schneider/Tallahassee Democrat)
“This eye can move up and down like a human eye does,” he said, showing where the cornea, about the size of a contact lens, will be placed on the outer circle.
“We have simulated the human eye,” he said.
The model using the 3D cornea print could lead to reducing the dependency on animal testing for products of the cornea, such as drops, gels and ointments emerging for market.
“There is no good system to screen them,” he said of emerging products. “We simulate the human system. The cornea will have several of the cells lined up and you can study how much drug is going through and what’s happening in a much more efficient manner and minimize animal testing.”
A long-term goal is to use the 3D printing for corneal transplants, he said.
“But that will take long-term studies,” he said. “We could make a cornea to order. That’s the benefit of the 3D model. The whole crux of 3D printing, you can make it a personalized approach to medicine.”
Path to innovation
The first challenge was envisioning how to come up with the cornea.
“The starting point was, we have to have print the cornea,” Sachdeva said. “A lot of things went into it. When you print the cornea, the bio-ink is very important. You have to formulate a bio-ink to use for the cornea that simulates the human characteristics.
“We had to use human cornea stromal cells.”
Sachdeva said the work done at FAMU differs from the U.K. study.
“They printed one cornea. One of my team members (Dinh) said it takes so much time, if you want to print six corneas, or 12 corneas, how do we do that? My team developed a high throughput printing system where in about 10 minutes, you can print about six corneas.”
Technically speaking, the FAMU team has accomplished the first high throughput cornea printing breakthrough in the U.S., Sachdeva said.
“High throughput cornea printing means that we can print multiple corneas in a matter of minutes using a specially designed scaffold by our laboratory,” he said. “This will save time, and hence, will increase efficiency."
He compared it to other automation process in other industries like punching multiple tablets in pharmaceutical manufacturing repeatedly of the same formulation.
The bio-ink which the team made “simulates the human eye more accurately for the collagen concentration than the U.K. model.
“We are also better characterizing our bio-ink for its flow properties so as to help future scientists when they want to print their corneas.”
Brainpower and a vision
Sachdeva is quick to credit to his team of Kutlehria, who works with optimization, characterization of bio ink along with evaluating cell growth, behavior and interactions within the printed structures, and Dinh, who focuses on the technology involved in advancing the print process.
Both say their goal is being part of a science breakthrough that will directly benefit the public.
“Knowledge of drugs, their actions and discoveries in the medical world always intrigued me since childhood,” said Kutlehria, a doctoral candidate in the College of Pharmacy and Pharmaceutical Sciences. “This impetus fueled me to pursue a career in pharmaceutical research. My objective is to better understand the diseases and bring changes that can transform patient’s life and they can see this world differently.”
FAMU research assistant Dinh said: “The ultimate goal of my research is to alleviate human suffering and I hope that my contributions in developing a 3D bio printed human cornea would help in the ongoing pursuit in curing blindness and eliminating waiting lists for organ donations."
The ongoing work has involved lot of weekends and late nights consuming scientific literature and holding long discussions.
“We have a good printer, but more than that is the innovation part,” Sachdeva said. “If you have the right team put together who can solve scientific problems, anything can be achievable in the world.
"It is the human brain that is the driver here,” he said. “We can do what Harvard and MIT can do.”