Jan 29, 2016 | By Alec

Biomedical 3D printing solutions, especially 3D bioprinted implantable human tissue, are still very much in the ‘laboratory’ phase, but a team of researchers from the University of Maryland’s Fisher Lab are already looking at how to save lives with it. They have set their sights on congenital heart disease (CHD), the most common type of birth defect in the world that affects nearly one percent of newborns, and are pioneering new custom-made 3D bioprinted grafts to correct these defects.

While perhaps not the most deadly of all birth defects, CHD is a particularly difficult one to combat. Affecting up to 40,000 newborn babies annually in the US alone, there are some procedures that can give these babies longer and healthier lives, but they’re not universally applicable. Especially problematic is the fact that CHD results in very specific defects that differ per person due to anatomical differences. Grafts can be implanted into the heart, but these need to perfectly adapted to suit the patient in question – which isn’t always possible. Current graft implants tend to suffer from progressive obstruction, infection, lack of growth potential, thromboembolitic complications, calcification and other negative long-term effects. In fact, graft failure rates are in the 70 to 100 percent range when looking at patients 10 15 years later.

Fortunately, 3D bioprinting advances offer an alternative through the development of patient-specific vascular grafts that are made from biodegradable materials. And the University of Maryland just happens to have some experts in this area at their department, namely Robert E. Fischell Professor and Chair John Fisher and members of his Tissue Engineering and Biomaterials Laboratory. They have been working on developing a production platform for these biodegradable scaffolds, and have just published a paper on their progress in Advanced Healthcare Materials. Main authors for the paper were PhD student Anthony Melchiorri, student Chelsea Kraynak and undergraduate Lucas Kimerer.

As they explain, 3D printing was immediately recognized for its potential to change approaches to medical challenges, though tissue engineering remains very complex. Though, as we’ve seen already, functional blood vessels can be 3D printed, those types of vessels are only suitable for large organs and other tissues, and not the heart. What’s more, CHD patients are in need of grafts with adequate mechanical strength immediately after fabrication.

They therefore set out to develop functional and fully 3D printed non-cellular vascular grafts that can be demonstrated in vivo. “Such a platform may eventually enable the production of more complex structures customized for experimental studies or clinical applications by incorporating customized macroscale geometry—like vessel bifurcations and curves—with controlled microscale architecture-like porosity and surface roughness,” they say.

In particular, they used a biocompatible material called PPF, which is short for poly propylene fumarate. This is a biodegrdable polyester that contains a carbon-carbon double bond along its backbone, which enables the material to establish links between polymer chains – characteristics that make it ideal for 3D printed and functional tissue scaffolding. To make it 3D printable, it was mixed with DEF (at a weight ratio of 5:4).

To actually 3D print it, the team relied on DLP stereolithography, a resin 3D printing technique that 3D prints in a vertical movement at room temperature. Through SolidWorks CAD designs based on MRI or CT imaging data, they actually managed to 3D print custom vascular grafts with this technique. 3D printing took place with an EnvisionTEC Perfactory P4 with Enhanced Resolution Module, with curing happening at a resolution of individual 50 μm layers of resin at “For mechanical characterization of the printed material, dogbone films were printed with thickness of 0.30 mm, an effective length of 7.0 mm, and a width of 2.0 mm,” they add.

These PPF scaffolds were found to adhere well to cell structures, and the team demonstrated their efficacy in the venous systems in the hearts of mice. This proved that by resorting to 3D printing for developing these vascular grafts, they can significantly reduce the steps necessary for the construction of scaffolding. What’s more, they saw that these PPF grafts exhibited the same mechanical properties of native vessels used in grafting procedures. They therefore believe that both 3D printing and this PPF material can greatly aid the development of customized vascular scaffolding, which can in turn greatly help people suffering from CHD.

 

 

Posted in 3D Printing Application

 

 

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