3D printed skin, with blood vessels

Pankaj Karande and Rensselaer Polytechnic Institute colleagues have developed 3D printed living skin, with blood vessels. which could integrate with host cells in grafts.

Until now, a significant barrier to integration has been the absence of a functioning vascular system.

Karande previously made two types of living human cells into “bio-inks,” and print them into a skin-like structure. He now includes human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells — with animal collagen and other structural cells typically found in a skin graft.

The cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks. 

Karande said more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings. But the grafts his team has created bring researchers closer to helping people with more discrete issues, like diabetic or pressure ulcers.

Click to view RPI video

Join ApplySci at the 12th Wearable Tech + Digital Health + Neurotech conference on February 11-12, 2020 at Quadrus Sand Hill Road.  Speakers include:  Zhenan Bao, Stanford – Vinod Khosla, Khosla Ventures – Mark Chevillet, Facebook – Shahin Farshchi, Lux Capital – Carla Pugh, Stanford – Nathan Intrator, Tel Aviv University | Neurosteer – Wei Gao, Caltech – Sergiu Pasca, Stanford – Rudy Tanzi, Harvard – Sheng Xu, UC San Diego – Dror Ben-Zeev, University of Washington – Mikael Eliasson, Roche

3D printed, vascularized heart, using patient’s cell, biological materials

Tel Aviv University professor Tal Dvir has printed a 3D vascularized engineered heart, including cells, blood vessels, ventricles and chambers,  using a patient’s own cell and biological materials.

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.

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3D printed bioreactor-grown bone for craniofacial surgery

Antonios MikosAlexander Tatara, and Rice colleagues are using a 3D printed mold, attached to a rib, to grow live bones to repair craniofacial injuries. Stem cells and blood vessels from the rib infiltrate scaffold material and replace it with natural, custom-fit bone.

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.

3D-printed, bluetooth-controlled ingestible capsule delivers drugs, senses environment

MIT’s Bob Langer and Giovanni Traverso have developed a 3D-printed, wirelessly-controlled, ingestible capsule that can  deliver drugs, sense environmental conditions, or both.  It can reside in the stomach for a month.  Data is sent to a user’s phone, and instructions from the phone are sent to the device.  The sensor could also communicate with other wearable and implantable devices, and send the combined data to a doctor.

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.

Join ApplySci at the 10th Wearable Tech + Digital Health + Neurotech Silicon Valley conference on February 21-22 at Stanford University — Featuring:  Zhenan BaoChristof KochVinod KhoslaWalter Greenleaf – Nathan IntratorJohn MattisonDavid EaglemanUnity Stoakes Shahin Farshchi Emmanuel Mignot Michael Snyder Joe Wang – Josh Duyan – Aviad Hai Anne Andrews Tan Le – Anima Anandkumar – Hugo Mercier

Proof of concept 3D printed cornea

Newcastle University’s Che Connon has developed proof-of-concept research that could lead to a 3D printed cornea.

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.

Click to view Newcastle University video

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3D, real-scale blood brain barrier model used to study new therapeutics

Gianni Ciofani  of ITT Pisa has created a device that reproduces a 1:1 scale model of the blood-brain barrier.  The combination of 3D printed artificial and biological components will allow the study of new therapeutic strategies to overcome the blood-brain barrier and treat brain diseases, including tumors, Alzheimers, and multiple sclerosis.

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.

Join ApplySci at Wearable Tech + Digital Health + Neurotech Silicon Valley on February 26-27, 2018 at Stanford University. Speakers include:  Vinod Khosla – Justin Sanchez – Brian Otis – Bryan Johnson – Zhenan Bao – Nathan Intrator – Carla Pugh – Jamshid Ghajar – Mark Kendall – Robert Greenberg – Darin Okuda – Jason Heikenfeld – Bob Knight – Phillip Alvelda – Paul Nuyujukian –  Peter Fischer – Tony Chahine – Shahin Farshchi – Ambar Bhattacharyya – Adam D’Augelli – Juan-Pablo Mas – Shreyas Shah– Walter Greenleaf – Jacobo Penide – David Sarno – Peter Fischer


3D-bioprinted human skin can replace animal testing, potentially be used in burns

José Luis Jorcano at Universidad Carlos III de Madrid has developed a 3D bioprinter capable of replicating the structure of skin. The human-like  skin that is produced  includes an epidermal layer that protects against the environment, and a collagen-producing dermis that provides elasticity and strength.

The bioink material  contains human plasma, and  primary human fibroblasts and keratinocytes obtained from biopsies.

Currently, 100 cm2 of the printed skin  is able to be produced in 35 minutes.

ApplySci’s 6th  Digital Health + NeuroTech Silicon Valley  –  February 7-8 2017 @ Stanford   |   Featuring:   Vinod Khosla – Tom Insel – Zhenan Bao – Phillip Alvelda – Nathan Intrator – John Rogers – Roozbeh Ghaffari –Tarun Wadhwa – Eythor Bender – Unity Stoakes – Mounir Zok – Sky Christopherson – Marcus Weldon – Krishna Shenoy – Karl Deisseroth – Shahin Farshchi – Casper de Clercq – Mary Lou Jepsen – Vivek Wadhwa – Dirk Schapeler – Miguel Nicolelis

3D printed renal architecture

Harvard’s Jennifer Lewis and Roche’s  Annie Moisan have used 3D printing to fabricate a small but critical subunit of a kidney.  The renal architecture contains living epithelial cells.

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.

Click to view Wyss Institute video.

ApplySci’s 6th   Wearable Tech + Digital Health + NeuroTech Silicon Valley  –  February 7-8 2017 @ Stanford   |   Featuring:   Vinod Khosla – Tom Insel – Zhenan Bao – Phillip Alvelda – Nathan Intrator – John Rogers – Mary Lou Jepsen – Vivek Wadhwa – Miguel Nicolelis – Roozbeh Ghaffari –Tarun Wadhwa – Eythor Bender – Unity Stoakes – Mounir Zok – Krishna Shenoy – Karl Deisseroth

3D printed gel model replicates brain folding mechanism

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.

Wearable Tech + Digital health San Francisco – April 5, 2016 @ the Mission Bay Conference Center

NeuroTech San Francisco – April 6, 2016 @ the Misson Bay Conference Center

Wearable Tech + Digital Health NYC – June 7, 2016 @ the New York Academy of Sciences

NeuroTech San Francisco – June 8, 2016 @ the New York Academy of Sciences

3D printed model for brain aneurysm surgery planning

Stratasys and the Jacobs Institute have used 3D printing for brain surgery planning in an effort to reduce risk. Anatomical models of a patient’s entire brain vessel anatomy were 3D printed before she underwent an aneurysm procedure.

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.