Senior Staff Writer

Short of having psychic abilities or a time machine, nobody knows for sure just how big the 3-D printing market will become or the full extent to which this incredible technology will change the world. But most people agree that the ability to instantly produce solid objects from a digital file will have a mind-blowing impact on nearly every aspect of our lives. Most would also agree that the healthcare industry will be among the most transformed by 3-D printing.

"I know it's going to revolutionize manufacturing, it's already beginning to, and the medical industry is going to be the first industry to benefit from it," Dorothy Baunach, CEO of OsteoSymbionics (Cleveland), a company that makes patient-specific craniofacial implants, told MDD.

Baunach said her company doesn't use 3-D printing in its production process yet but has started to experiment with the technology.

Within med-tech, there are a few sectors that stand out as being most likely beneficiaries of the 3-D printing era. Orthopedics is the most obvious but there are also a lot of opportunities for the technology in cardiovascular, diagnostics, and, ultimately, organ transplants.

"We're not alone in thinking [3-D printing] is going to play a tremendous role in the medical space," Robert Urban, head of Johnson & Johnson Boston Innovation Center, told MDD.

DePuy Synthes Products (Warsaw, Indiana) and J&J Innovation recently formed a strategic collaboration with Tissue Regeneration Systems (Ann Arbor, Michigan) to develop patient-specific, resorbable implants for large bone segmental defect treatment in trauma and orthopedic oncology. "We can't promise on timelines at this point, but they should be tested quickly."

Printing human tissue

At Harvard University (Cambridge, Massachusetts), Jennifer Lewis and her team are working with 3-D printing of soft functional materials for use in a variety of applications, including microvascular architectures for cell culture and tissue engineering.

Using a custom-built four-headed 3-D printer and a special type of ink, the Lewis Lab has created tissue interlaced with blood vessels, which could be a major breakthrough for creating artificial organs. The researchers reported their progress earlier this year in Advanced Materials. The tissue is the first made through 3-D printing to include potentially functional blood vessels embedded among multiple, patterned cell types, the team noted.

Lewis' group created hollow, tube-like structures within a mesh of printed cells using an ink that liquefies as it cools. The tissue is built by the 3-D printer in layers. A gelatin-based ink acts as extracellular matrix and two other inks contained the gelatin material and either mouse or human skin cells. All the inks used are viscous enough to maintain their structure after being laid down by the printer, the scientists said.

The team printed tracks of this ink amongst the others. After chilling the patch of printed tissue, the researchers applied a light vacuum to remove the special ink, leaving behind empty channels within the structure. Then, cells that normally line blood vessels in the body can be infused into the channels. Lewis said this is a foundational step toward organ printing or regeneration.

The smallest channels printed were about 75 micrometers in diameter, which is much larger than the tiny capillaries that exchange nutrients and waste throughout the body. The idea is that the 3-D printing method will set the overall architecture of blood vessels within artificial tissue and then smaller blood vessels will develop along with the rest of the tissue.

As 3-D printing evolves, the technology could easily touch every corner of the med-tech industry to some extent, including the way drugs and devices are developed and tested. Organovo (San Diego), a company that designs and creates functional human tissues using 3-D bioprinting, is working with the National Eye Institute (NEI) and the National Center for Advancing Translational Sciences (NCATS) (both Bethesda, Maryland) to develop better and more clinically predictive tissue models using Organovo's NovoGen MMX Bioprinter.

The company announced the partnership in January, noting that it would help scientists develop more reliable tools for bringing safer, more effective treatments to patients on a faster timeline. Organovo said it would collaborate with NCATS and NEI in using the NovoGen Bioprinting platform to create three-dimensional, architecturally correct, functional living tissues.

"Researchers who develop new therapies for patients are too often hampered by animal models and traditional cell culture models that are poor predictors of drug efficacy and toxicity in human beings," said Keith Murphy, Organovo's CEO. "Our 3-D printer creates living human tissues that more closely reproduce in vivo human tissues. In collaboration with NIH, which has worked to highlight and address the critical need for better models that can lead to better drugs, we hope to create tissue models that give researchers a much more accurate view of how drugs will behave in human beings before those drugs ever enter clinical trials."

Paul Sieving, director of NEI, said the technology could provide the organization with a renewable and easy-to-manipulate source of functional eye tissue. "Printable eye tissue could be used to identify disease pathways and to screen for and discover new therapeutic drugs."

Organovo is making similar strides with its 3D Liver tissue, which it is offering to clients for the purposes of toxicity testing. The company has begun signing research service contracts and is in discussions with additional customers for near-term needs, in a limited initial release of this service. All testing will be performed at Organovo's facility by the company's laboratory services tissue experts. Organovo said the long lasting viability and function of the tissue allows for extended study durations in vitro, enabling the assessment of the effects of low dose or repeated dosing regimens across a spectrum of biochemical, molecular, and histologic end points.

Organovo's bioprinting process centers around the identification of key architectural and compositional elements of a target tissue, and the creation of a design that can be used by a bioprinter to generate that tissue in the laboratory environment. Once a tissue design is established, the first step is to develop the bioprocess protocols required to generate the multi-cellular building blocks – also called bio-ink – from the cells that will be used to build the target tissue, the company said.

The bio-ink building blocks are then dispensed from a bioprinter, using a layer-by-layer approach that is scaled for the target output. Bio-inert hydrogel components may be used as supports, as tissues are built up vertically to achieve three-dimensionality, or as fillers to create channels or void spaces within tissues to mimic features of native tissue, the company explained. Organovo said the bioprinting process can be tailored to produce tissues in a variety of formats, from micro-scale tissues contained in standard multi-well tissue culture plates, to larger structures suitable for placement onto bioreactors for biomechanical conditioning prior to use.

Printing spines and hips

Last month Medicrea (New York), a company that specializes in the development of surgical technologies for treating complex spinal pathologies, reported that a surgeon in France performed spinal fusion surgery using customized spine cages created by Medicrea with a 3-D printer.

The company said it developed the UNiD service to bring customization to spinal fusion surgery, which is performed to correct severe spinal deformities. With the support of specific softwares and advanced imaging, the UNiD ALIF customized cages made of Poly Ether Ketone Ketone (PEKK) exactly reproduce the anatomic details of a patient's vertebral plates, according to Medicrea.

Vincent Fiere performed the first operation using the UniD ALIF device on May 28 at the Hospital Jean Mermoz (Lyon, France). "The intersomatic cage, specifically printed by Medicrea for my patient, positioned itself automatically in the natural space between the vertebrae and molded ideally with the spine by joining intimately with the end plates, despite their relative asymmetry and irregularity," Fiere said. "I could also very precisely perform the restoration of the disc height and simultaneously correct the degree of lumbar lordosis using plans I had made several days before the operation with the help of Medicrea's Surgimap software tool."

The UNiD ALIF intersomatic anatomical inter-body device was developed from a 3-D digital file created from the extraction and treatment of pre-operatory scanner images of the patient, the company noted.

Researchers in the UK have also made recent progress using 3-D printing for orthopedic procedures. Doctors at the University of Southampton performed hip surgery with a 3-D printed implant and bone stem cell graft. The hip, made from titanium, was designed using the patient's CT scan and computer-aided design and computer-aided manufacturing technology.

The implant will provide a new socket for the ball of the femur bone to enter, the researchers said. Behind the implant and between the pelvis, doctors have inserted a graft containing bone stem cells. The graft acts as a filler for the loss of bone. The patient's own bone marrow cells have been added to the graft to provide a source of bone stem cells to encourage bone regeneration behind and around the implant.

Douglas Dunlop, a consultant orthopedic surgeon, conducted the operation at Southampton General Hospital. "The benefits to the patient through this pioneering procedure are numerous. The titanium used to make the hip is more durable and has been printed to match the patient's exact measurements, this should improve fit and could reduce the risk of having to have another surgery," Dunlop said. "The bone graft material that has been used has excellent biocompatibility and strength and will fill the defect behind the bone well, fusing it all together."

For the patient, Meryl Richards, from Hampshire, the procedure means an end to her hip troubles, which began In 1977 after a traffic accident. Since the accident, Richards has had six operations to mend her hip.

"The way medicine has evolved is fantastic. I hope that this will be the last time that I have to have a hip operation," Richards said. "I feel excited to have this pioneering surgery and I can see what a benefit it will have to me."

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