New 3D printing tech empowers surgeons at a nano scale

A 3D printer that can produce detailed models narrower than a human hair is helping experts in medical robotics at Imperial's Hamlyn Centre.

The technology, utilising the Photonic Professional GT machine by Nanoscribe and funded by EPSRC, is allowing researchers at the Hamlyn Centre to develop previously impossible medical therapies, devices and procedures. 

These include swimming microrobots for targeted drug delivery as well as ultra-small instruments for microsurgery. Thanks to the work of Hamlyn researchers and their collaborators around the world, these techniques could allow oncologists to deliver cancer drugs that operate like targeted missiles rather than affecting a wider part of the body. Eye surgeons could also benefit through the use of new nano tools for delicate operations to the back of the eye, minimising the risk of damage.

The Hamlyn Centre’s Director Professor Guang-Zhong Yangshowcased the work to President Xi Jinping and other senior Chinese and British officials during their visit to the College on 21 October.

The Imperial researchers use a cutting-edge technique known as Two Photon Polymerisation, where a controlled point of pulsed laser is used to polymerise – in other words, joining together molecules – or solidify a liquid photoresist (a light-sensitive material). By moving a laser with great precision, a structure can be built layer-by-layer in the same manner as standard 3D printers, but at a nano scale. 

Great Wall gift

 

The group can build 3D models and structures with advanced features as small as 150 nanometres – about the same size as the almost-invisible pits imprinted on CDs. This could help surgeons develop three-dimensional tools with force-sensing capabilities, giving tactile feedback, for use at a microscopic scale in surgery. When President Xi visited the Hamlyn Centre in October, he and the Duke of York were presented with gifts demonstrating this pioneering technique. 

Maura Power, a PhD student supervised by Professor Yang at the Hamlyn Centre, explains, “A section of the Great Wall of China was printed on to a square of silicon at one millionth of its true scale. The section of wall is just over 100 micrometres long, which is the same as the width of a typical human hair. An image of the printed wall was acquired using a Scanning Electron Microscope.

The length of the letters in this image are approximately the same diameter as that of human red blood cells. This microscope picture was mounted next to the silicon wafer in a frame which was wrapped in red ribbon and presented to President Xi by Professor Guang-Zhong Yang. 

“For Prince Andrew, a panda leaping over a bamboo was printed to the tip of a needle and also presented in a small frame. The height of the panda is approximately 50 micrometres, or half the width of a human hair.”

Imperial College London

An Essential Step toward Printing Living Tissues

A new 3D printing method developed by Wyss Core Faculty member
Jennifer Lewis and her team uses multiple print heads and customized
"inks" to create complex living tissue constructs, complete with tiny
blood vessels.

A new bioprinting method developed at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard School of Engineering and Applied Sciences (SEAS) creates intricately patterned 3D tissue constructs with multiple types of cells and tiny blood vessels. 

The work represents a major step toward a longstanding goal of tissue engineers: creating human tissue constructs realistic enough to test drug safety and effectiveness.

The method also represents an early but important step toward building fully functional replacements for injured or diseased tissue that can be designed from CAT scan data using computer-aided design (CAD), printed in 3D at the push of a button, and used by surgeons to repair or replace damaged tissue.

"This is the foundational step toward creating 3D living tissue," said Jennifer Lewis, Ph.D., senior author of the study, who is a Core Faculty Member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, and the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard SEAS. Along with lead author David Kolesky, a graduate student in SEAS and the Wyss Institute, her team reported the results February 18 in the journal Advanced Materials.

Tissue engineers have tried for years to produce lab-grown vascularized human tissues robust enough to serve as replacements for damaged human tissue. Others have printed human tissue before, but they have been limited to thin slices of tissue about a third as thick as a dime. When scientists try to print thicker layers of tissue, cells on the interior starve for oxygen and nutrients, and have no good way of removing carbon dioxide and other waste. So they suffocate and die.

Nature gets around this problem by permeating tissue with a network of tiny, thin-walled blood vessels that nourish the tissue and remove waste, so Kolesky and Lewis set out to mimic this key function.

3D printing excels at creating intricately detailed 3D structures, typically from inert materials like plastic or metal. In the past, Lewis and her team have pioneered a broad range of novel inks that solidify into materials with useful electrical and mechanical properties. These inks enable 3D printing to go beyond form to embed functionality.

To print 3D tissue constructs with a predefined pattern, the researchers needed functional inks with useful biological properties, so they developed several "bio-inks" — tissue-friendly inks containing key ingredients of living tissues. One ink contained extracellular matrix, the biological material that knits cells into tissues. A second ink contained both extracellular matrix and living cells.

To create blood vessels, they developed a third ink with an unusual property: it melts as it is cools, rather than as it warms. This allowed the scientists to first print an interconnected network of filaments, then melt them by chilling the material and suction the liquid out to create a network of hollow tubes, or vessels.

The Harvard team then road-tested the method to assess its power and versatility. They printed 3D tissue constructs with a variety of architectures, culminating in an intricately patterned construct containing blood vessels and three different types of cells — a structure approaching the complexity of solid tissues.

Moreover, when they injected human endothelial cells into the vascular network, those cells regrew the blood-vessel lining. Keeping cells alive and growing in the tissue construct represents an important step toward printing human tissues. "Ideally, we want biology to do as much of the job of as possible," Lewis said.

Lewis and her team are now focused on creating functional 3D tissues that are realistic enough to screen drugs for safety and effectiveness. "That's where the immediate potential for impact is," Lewis said.

Scientists could also use the printed tissue constructs to shed light on activities of living tissue that require complex architecture, such as wound healing, blood vessel growth, or tumor development.

"Tissue engineers have been waiting for a method like this," said Don Ingber, M.D., Ph.D., Wyss Institute Founding Director. "The ability to form functional vascular networks in 3D tissues before they are implanted not only enables thicker tissues to be formed, it also raises the possibility of surgically connecting these networks to the natural vasculature to promote immediate perfusion of the implanted tissue, which should greatly increase their engraftment and survival".

In addition to Lewis and Kolesky, the Wyss Institute research team also included Ryan L. Truby, A. Sydney Gladman, Travis A. Busbee, SEAS graduate students, and Kimberly A. Homan, Ph.D., a postdoctoral fellow at SEAS. The work was funded by the Wyss Institute for Biologically Inspired Engineering and the Harvard Materials Research Science and Engineering Center.

Source: http://wyss.harvard.edu/viewpressrelease/141/

Cells from the eye are inkjet printed for the first time

Close-up of retinal cells in a jet
IOP Publising, Biofabrication

A group of researchers from the UK have used inkjet printing technology to successfully print cells taken from the eye for the very first time.

The breakthrough, which has been detailed in a paper published today, 18 December, in IOP Publishing’s journal Biofabrication, could lead to the production of artificial tissue grafts made from the variety of cells found in the human retina and may aid in the search to cure blindness.

At the moment the results are preliminary and provide proof-of-principle that an inkjet printer can be used to print two types of cells from the retina of adult rats―ganglion cells and glial cells. This is the first time the technology has been used successfully to print mature central nervous system cells and the results showed that printed cells remained healthy and retained their ability to survive and grow in culture.

Co-authors of the study Professor Keith Martin and Dr Barbara Lorber, from the John van Geest Centre for Brain Repair, University of Cambridge, said: “The loss of nerve cells in the retina is a feature of many blinding eye diseases. The retina is an exquisitely organised structure where the precise arrangement of cells in relation to one another is critical for effective visual function”.

“Our study has shown, for the first time, that cells derived from the mature central nervous system, the eye, can be printed using a piezoelectric inkjet printer. Although our results are preliminary and much more work is still required, the aim is to develop this technology for use in retinal repair in the future.”

Printed glia cells
IOP Publising,Biofabrication

The ability to arrange cells into highly defined patterns and structures has recently elevated the use of 3D printing in the biomedical sciences to create cell-based structures for use in regenerative medicine.

In their study, the researchers used a piezoelectric inkjet printer device that ejected the cells through a sub-millimetre diameter nozzle when a specific electrical pulse was applied. They also used high speed video technology to record the printing process with high resolution and optimised their procedures accordingly.

“In order for a fluid to print well from an inkjet print head, its properties, such as viscosity and surface tension, need to conform to a fairly narrow range of values. Adding cells to the fluid complicates its properties significantly,” commented Dr Wen-Kai Hsiao, another member of the team based at the Inkjet Research Centre in Cambridge.

Once printed, a number of tests were performed on each type of cell to see how many of the cells survived the process and how it affected their ability to survive and grow.

The cells derived from the retina of the rats were retinal ganglion cells, which transmit information from the eye to certain parts of the brain, and glial cells, which provide support and protection for neurons.

“We plan to extend this study to print other cells of the retina and to investigate if light-sensitive photoreceptors can be successfully printed using inkjet technology. In addition, we would like to further develop our printing process to be suitable for commercial, multi-nozzle print heads,” Professor Martin concluded.

The research was undertaken by Dr. Barbara Lorber, also at the John van Geest Centre for Brain Repair, in collaboration with Dr. Wen-Kai Hsiao and Prof. Ian Hutchings from the Inkjet Research Centre, University of Cambridge. The work was funded by Fight for Sight, the van Geest Foundation and the EPSRC.

From Wednesday 18 December, the paper can be downloaded fromhttp://iopscience.iop.org/1758-5090/6/1/015001/article

Source: http://www.iop.org/news/13/dec/page_62164.html