A biopsy of fatty tissue was taken from patients. Cellular and a-cellular materials were separated. While the cells were reprogrammed to become pluripotent stem cells, the extracellular matrix were processed into a personalized hydrogel that served as printing “ink.” After being mixed with the hydrogel, the cells were efficiently differentiated to cardiac or endothelial cells to create patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire heart.
Dvir believes that this “3D-printed thick, vascularized and perfusable cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient” reduces the risk of implant rejection.
The team now plans on culturing the printed hearts and “teaching them to behave” like hearts, then transplanting them in animal models.
Current reconstruction methods use a patient’s own bone graft tissues, harvested from the lower leg, hip and shoulder.
According to Mikos: “We chose to use ribs because they’re easily accessed and a rich source of stem cells and vessels, which infiltrate the scaffold and grow into new bone tissue that matches the patient.” New bone can potentially be grown on multiple ribs, simultaneously.
The technology has only been tested on animals, but shows promise, with custom geometry and a reduced risk of rejection.
The technology could improve drug delivery in conditions where drugs must be taken over a long period. It can also sense infections, allergic reactions, or other events, and then release a drug accordingly.
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Stem cells from a healthy donor cornea were mixed with alginate and collagen to create a printable bio-ink. A 3D printer extruded the bio-ink in concentric circles to form the shape of a human cornea in less then 10 minutes. The stem cells then grew.
According to Connon: “Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer. This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”
The team demonstrated that they could build a cornea to match a patient’s unique specifications, but said that it will be several years before this might be used for transplants.
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A laser that scans through a liquid photopolymer and solidifies the material locally and layer by layer built complex 3D objects with submicron resolution. This enabled the researchers to engineer an accurate real-scale model of the BBB made from a photopolymer resin. Mimicking the brain microcapillaries, the model consists of a microfluidic system of 50 parallel cylindrical channels connected by junctions and featuring pores on the cylinder walls. Each of the tubular structures has a diameter of 10 μm and pores of 1 μm diameter uniformly distributed on all cylinders. After the fabrication of the complex scaffold-like polymer structure, endothelial cells were cultivated around the porous microcapillary system. Covering the 3D printed structure, the cells built a biological barrier resulting in a biohybrid system which resembles its natural model. The device is few millimeters big and fluids can pass through it at the same pressure as blood in brain vessels.
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Earlier bioprinting approaches were adapted to form thick tissues. A 3D-printed silicone gasket was used to cast an engineered extracellular matrix as a base layer. “Fugitive ink” was printed in a shape similar to that of renal proximal tubules, and encapsulated with another layer of extracellular matrix.
The in vitro model functions like living kidney tissue, representing a significant advance from traditional 2D cell culture. The result could be an implant or assistive device, and/or more effective clinical trials.
L. Mahadevan and Harvard colleagues have used 3D printing to replicate a folding human brain. The goal is to understand how brain folds are related to disease. While many molecular processes determine cellular events, the study shows that what ultimately causes the brain to fold is a mechanical instability associated with buckling.
A 3D gel model of a smooth fetal brain was created based on MRI images. To mimic cortical expansion, the gel brain was immersed in a solvent that is absorbed by the outer layer, causing it to swell relative to the deeper regions. The resulting compression led to the formation of folds similar in size and shape to real brains.
In humans, folding begins in fetal brains at the 20th week of gestation, and is completed at a year and a half. The number, size, shape and position of neuronal cells during brain growth lead to the expansion of the cortex (gray matter), relative to the underlying white matter. The scientists said that this puts the cortex under compression, leading to a mechanical instability that causes it to crease locally. They believe that if a part of the brain does not grow properly, or if the global geometry is disrupted, the major folds may not be in the right place, which may cause dysfunction.
The replica, built of a polymer that mimics human tissue, allowing the surgeons to plan their approach and practice the operation, was based on CT scans.
In this case. the accurate model enabled surgeons to fine-tune the procedure. “While we were doing that mock procedure, we realized that we had to change some of the tools we wanted to use, given her anatomy,” said Adnan Siddiqui, Jacobs’ Chief Medical Officer.
Feinberg described his progress: “We’ve been able to take MRI images of coronary arteries and 3-D images of embryonic hearts and 3-D bioprint them with unprecedented resolution and quality out of very soft materials like collagens, alginates and fibrins.”
The next step is to incorporate real heart cells into these 3-D printed tissue structures, providing a scaffold to help form contractile muscle.