Tag: 3D printing

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Groundbreaking Spinal Scaffold Allows Nerve Fibres to Regrow

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New research combines 3D printing, stem cell biology, and lab-grown tissues for possible treatments of spinal cord injuries. Photo provided by: McAlpine Research Group, University of Minnesota

For the first time, a research team at the University of Minnesota Twin Cities demonstrated a groundbreaking process that combines 3D printing, stem cell biology, and lab-grown tissues for spinal cord injury recovery. 

The study was recently published in Advanced Healthcare Materials. Currently, there is no way to completely reverse the damage and paralysis from the injury. A major challenge is the death of nerve cells and the inability of nerve fibres to regrow across the injury site. This new research tackles this problem head-on.

The method involves creating a unique 3D-printed framework for lab-grown organs, called an organoid scaffold, with microscopic channels. These channels are then populated with regionally specific spinal neural progenitor cells (sNPCs), which are cells derived from human adult stem cells that have the capacity to divide and differentiate into specific types of mature cells.

“We use the 3D printed channels of the scaffold to direct the growth of the stem cells, which ensures the new nerve fibres grow in the desired way,” said Guebum Han, a former University of Minnesota mechanical engineering postdoctoral researcher and first author on the paper who currently works at Intel Corporation. “This method creates a relay system that when placed in the spinal cord bypasses the damaged area.”

n their study, the researchers transplanted these scaffolds into rats with spinal cords that were completely severed. The cells successfully differentiated into neurons and extended their nerve fibres in both directions – rostral (toward the head) and caudal (toward the tail) – to form new connections with the host’s existing nerve circuits. 

The new nerve cells integrated seamlessly into the host spinal cord tissue over time, leading to significant functional recovery in the rats.

“Regenerative medicine has brought about a new era in spinal cord injury research,” said Ann Parr, professor of neurosurgery at the University of Minnesota. “Our laboratory is excited to explore the future potential of our ‘mini spinal cords’ for clinical translation.”

While the research is in its beginning stages, it offers a new avenue of hope for those with spinal cord injuries. The team hopes to scale up production and continue developing this combination of technologies for future clinical applications.

Source: University of Minnesota

Categories : NeurologyTags :

Researchers 3D-print Functional Human Brain Tissue

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AI-generated image illustrating 3-D tissue printing

A team of scientists has developed the first 3D-printed brain tissue that can grow and function like typical brain tissue. This has important implications for scientists studying the brain and working on treatments for a broad range of neurological and neurodevelopmental disorders, such as Alzheimer’s and Parkinson’s disease.

“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” says Su-Chun Zhang, professor of neuroscience and neurology at UW-Madison’s Waisman Center. “It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders.”

Printing methods have limited the success of previous attempts to print brain tissue, according to Zhang and Yuanwei Yan, a scientist in Zhang’s lab. The group behind the new 3D-printing process described their method today in the journal Cell Stem Cell.

Instead of using the traditional 3D-printing approach, stacking layers vertically, the researchers went horizontally. They situated brain cells, neurons grown from induced pluripotent stem cells, in a softer “bio-ink” gel than previous attempts had employed.

“The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other,” Zhang says.

The cells are laid next to each other like pencils laid next to each other on a tabletop.

“Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media,” Yan says.

The results speak for themselves – which is to say, the cells can speak to each other. The printed cells reach through the medium to form connections inside each printed layer as well as across layers, forming networks comparable to human brains. The neurons communicate, send signals, interact with each other through neurotransmitters, and even form proper networks with support cells that were added to the printed tissue.

“We printed the cerebral cortex and the striatum and what we found was quite striking,” Zhang says. “Even when we printed different cells belonging to different parts of the brain, they were still able to talk to each other in a very special and specific way.”

The printing technique offers precision – control over the types and arrangement of cells – not found in brain organoids, miniature organs used to study brains. The organoids grow with less organisation and control.

“Our lab is very special in that we are able to produce pretty much any type of neurons at any time. Then we can piece them together at almost any time and in whatever way we like,” Zhang says. “Because we can print the tissue by design, we can have a defined system to look at how our human brain network operates. We can look very specifically at how the nerve cells talk to each other under certain conditions because we can print exactly what we want.”

That specificity provides flexibility. The printed brain tissue could be used to study signaling between cells in Down syndrome, interactions between healthy tissue and neighboring tissue affected by Alzheimer’s, testing new drug candidates, or even watching the brain grow.

“In the past, we have often looked at one thing at a time, which means we often miss some critical components. Our brain operates in networks. We want to print brain tissue this way because cells do not operate by themselves. They talk to each other. This is how our brain works and it has to be studied all together like this to truly understand it,” Zhang says. “Our brain tissue could be used to study almost every major aspect of what many people at the Waisman Center are working on. It can be used to look at the molecular mechanisms underlying brain development, human development, developmental disabilities, neurodegenerative disorders, and more.”

The new printing technique should also be accessible to many labs. It does not require special bio-printing equipment or culturing methods to keep the tissue healthy, and can be studied in depth with microscopes, standard imaging techniques and electrodes already common in the field.

The researchers would like to explore the potential of specialization, though, further improving their bio-ink and refining their equipment to allow for specific orientations of cells within their printed tissue..

“Right now, our printer is a benchtop commercialised one,” Yan says. “We can make some specialised improvements to help us print specific types of brain tissue on-demand.”

Source: University of Wisconsin-Madison

Categories : Regenerative MedicineTags :

Using Fat Tissue, Researchers 3D-Print Skin that Contains Hair Precursors

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AI art image created using Gencraft

Fat tissue holds the key to 3D printing layered living skin and potentially hair follicles, according to researchers who recently harnessed fat cells and supporting structures from clinically procured human tissue to precisely correct injuries in rats. The advancement could have implications for reconstructive facial surgery and even hair growth treatments for humans.

The team’s findings published in Bioactive Materials, and the team received a patent in February for the bioprinting technology it developed and used in this study.

“Reconstructive surgery to correct trauma to the face or head from injury or disease is usually imperfect, resulting in scarring or permanent hair loss,” said Ibrahim T. Ozbolat, professor of engineering science and mechanics, of biomedical engineering and of neurosurgery at Penn State, who led the international collaboration that conducted the work. “With this work, we demonstrate bioprinted, full thickness skin with the potential to grow hair in rats. That’s a step closer to being able to achieve more natural-looking and aesthetically pleasing head and face reconstruction in humans.”

While scientists have previously 3D bioprinted thin layers of skin, Ozbolat and his team are the first to intraoperatively print a full, living system of multiple skin layers, including the bottom-most layer or hypodermis. Intraoperatively refers to the ability to print the tissue during surgery, meaning the approach may be used to more immediately and seamlessly repair damaged skin, the researchers said. The top layer — the epidermis that serves as visible skin — forms with support from the middle layer on its own, so it doesn’t require printing. The hypodermis, made of connective tissue and fat, provides structure and support over the skull.

“The hypodermis is directly involved in the process by which stem cells become fat,” Ozbolat said. “This process is critical to several vital processes, including wound-healing. It also has a role in hair follicle cycling, specifically in facilitating hair growth.”

The researchers started with human adipose, or fat, tissue obtained from patients undergoing surgery at Penn State Health Milton S. Hershey Medical Center. Collaborator Dino J. Ravnic, associate professor of surgery in the Division of Plastic Surgery at Penn State College of Medicine, led his lab in obtaining the fat for extraction of the extracellular matrix to make one component of the bioink.

Ravnic’s team also obtained stem cells, which have the potential to mature into several different cell types if provided the correct environment, from the adipose tissue to make another bioink component. Each component was loaded into one of three compartments in the bioprinter. The third compartment was filled with a clotting solution that helps the other components properly bind onto the injured site.

“The three compartments allow us to co-print the matrix-fibrinogen mixture along with the stem cells with precise control,” Ozbolat said. “We printed directly into the injury site with the target of forming the hypodermis, which helps with wound healing, hair follicle generation, temperature regulation and more.”

They achieved both the hypodermis and dermis layers, with the epidermis forming within two weeks by itself.

“We conducted three sets of studies in rats to better understand the role of the adipose matrix, and we found the co-delivery of the matrix and stem cells was crucial to hypodermal formation,” Ozbolat said. “It doesn’t work effectively with just the cells or just the matrix – it has to be at the same time.”

They also found that the hypodermis contained downgrowths, the initial stage of early hair follicle formation. According to the researchers, while fat cells do not directly contribute to the cellular structure of hair follicles, they are involved in their regulation and maintenance.

“In our experiments, the fat cells may have altered the extracellular matrix to be more supportive for downgrowth formation,” Ozbolat said. “We are working to advance this, to mature the hair follicles with controlled density, directionality and growth.”

According to Ozbolat, the ability to precisely grow hair in injured or diseased sites of trauma can limit how natural reconstructive surgery may appear. He said that this work offers a “hopeful path forward,” especially in combination with other projects from his lab involving printing bone and investigating how to match pigmentation across a range of skin tones.

Source: Penn State

Categories : Implants and ProsthesesTags :

‘Cyberpunk’ Inspired Finger Prostheses will be Available to All via 3D Printing

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A groundbreaking, easy-to-use 3D printable finger prosthesis created by a recent University of Houston graduate could offer amputees a low-cost solution to restore finger functionality. David Edquilang first designed Lunet, which doesn’t need metal fasteners, adhesives or special tools to assemble, as an undergraduate student at the Gerald D. Hines College of Architecture and Design. While standard prostheses can cost thousands of dollars, Edquilang aims to make his design open access on the internet, instead of selling it.

Edquilang explains: “Lunet began when I decided to design and 3D print prototype finger mechanisms for a prosthetic hand for fun in my free time. 2 weeks and 18 prototypes later, I created a mechanism and finger structure that closely replicated the range of motion of real fingers.”

Edquilang’s mentor at UH was Associate Professor Jeff Feng, co-director of UH’s Industrial Design program. Through a partnership with Harris Health System, Feng learned of a patient who had her fingers amputated due to frostbite. Inspired by working on an upper limb prosthesis Edquilang previously developed with student Niell Gorman, working closely with Professor Feng, Edquilang created prosthetic fingers that returned mobility to the patient, allowing her to pick up objects again.

Edquilang continues: “My professor and I were then referred to a finger amputee who lost 3 of her fingers. I applied the mechanism I created to design a finger prosthesis for her. Nearly 40 design iterations and multiple rounds of patient testing were performed to ultimately create a functional prosthesis that fit her.

His “breakthrough” came from a literal break in his design.

“After we finished working with this amputee patient, I continued to tinker with my finger designs. I intentionally broke one of my finger prototypes to see where its structural weakpoint is. It broke at the distal knuckle. This led to me having a breakthrough in the design. I added a linkage that replaces the previously rigid distal knuckle, and I stumbled upon inventing a novel finger mechanism that was more flexible and nearly unbreakable. I then set on refining the design to be more functional, easily 3D printable, and more visually appealing. Inspiration from cyberpunk art and fighter jets influenced the design. 28 design iterations and a myriad of prototypes later resulted in Lunet.”

“It feels great knowing you have the capability to positively impact people’s lives and give them help they otherwise wouldn’t be able to get,” said Edquilang.

“Not every good idea needs to be turned into a business. Sometimes, the best ideas just need to be put out there ,” said Edquilang, who graduated with a Bachelor of Science in Industrial Design last year. “Medical insurance will often not cover the cost of a finger prosthesis, since it is not considered vital enough compared to an arm or leg. Making Lunet available online for free will allow it to help the greatest number of people.”

Lunet wins awards

The prosthetic design garnered Edquilang a 2023 Red Dot: Luminary award, the highest level of recognition accorded at the Red Dot Award: Design Concept. He and Feng took home the coveted accolade at Red Dot’s ceremony last month in Singapore.

“Good results come from dedication. Extraordinary results come from experimentation. Incredible results come from a combination of both,” he said upon winning the award. He has also received a number of other accolades, including iFDesign, and national runner up for the James Dyson Award.

“David’s recent success in winning the most prestigious design awards across the world is the best manifestation of the unparalleled education and training students experience in our Industrial Design program,” Feng said. “Built upon a belief that every student is a creative individual, the program pedagogy focuses on methods of cultivating innovative minds, which is enforced with rigorous professional training.”

Lunet’s geometry inspired its name

Lunet is made up of two common types of 3D printed plastics: polylactic acid and thermoplastic polyurethane. Each finger is made up of four parts held together by plastic pins. Edquilang describes arcs and circular orbits as the foundation for the motion of the finger mechanism. The geometric basis of the design evoked the idea that the prosthesis orbits around the user’s joints like a moon, or lunet, hence the name.

Another element of Lunet’s uniqueness is that it is nearly impossible to break; other finger prosthetics can be complicated and require many parts.

“The problem with higher mechanical complexity is that these designs are less durable,” Edquilang said. “The more parts you have, the more points of failure. You need to make prosthetic fingers robust and as strong as possible, so it doesn’t break under normal use, yet you want the design to be simple. This was one of the greatest challenges in making Lunet.”

He encourages other design students not to be afraid to experiment and fail because that is often how one can learn to improve the most.

“Where the world has an abundance of problems, designers have an abundance of talent, and we should not be selfish with it,” Edquilang said.

Source: University of Houston

Categories : Neurology Regenerative MedicineTags :

3D-Printed Structures Hold Promise for Repair of Traumatic Brain Injuries

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Researchers at the University of Oxford have produced an engineered tissue representing a simplified cerebral cortex by 3D printing human stem cells. The results, published in the journal Nature Communications, showed that, when implanted into mouse brain slices, the structures became integrated with the host tissue.

The breakthrough technique could lead to tailored repairs for brain injuries. The researchers demonstrated for the first time that neural cells can be 3D-printed to mimic the architecture of the cerebral cortex.

Brain injuries, including those caused by trauma, stroke and surgery for brain tumours, typically result in significant damage to the cerebral cortex. For example, each year, around 70 million people globally suffer from traumatic brain injury (TBI), with 5 million of these cases being severe or fatal. Currently, there are no effective treatments for severe brain injuries, leading to serious impacts on quality of life.

Tissue regenerative therapies, especially those in which patients are given implants derived from their own stem cells, could be a promising route to treat brain injuries in the future. Up to now, however, there has been no method to ensure that implanted stem cells mimic the architecture of the brain.

In this new study, the University of Oxford researchers fabricated a two-layered brain tissue by 3D printing human neural stem cells. When implanted into mouse brain slices, the cells showed convincing structural and functional integration with the host tissue.

Lead author Dr Yongcheng Jin (Department of Chemistry, University of Oxford) said: ‘This advance marks a significant step towards the fabrication of materials with the full structure and function of natural brain tissues. The work will provide a unique opportunity to explore the workings of the human cortex and, in the long term, it will offer hope to individuals who sustain brain injuries.’

The cortical structure was made from human induced pluripotent stem cells (hiPSCs), which have the potential to produce the cell types found in most human tissues. A key advantage of using hiPSCs for tissue repair is that they can be easily derived from cells harvested from patients themselves, and therefore would not trigger an immune response.

The hiPSCs were differentiated into neural progenitor cells for two different layers of the cerebral cortex, by using specific combinations of growth factors and chemicals. The cells were then suspended in solution to generate two ‘bioinks’, which were then printed to produce a two-layered structure. In culture, the printed tissues maintained their layered cellular architecture for weeks, as indicated by the expression of layer-specific biomarkers.

When the printed tissues were implanted into mouse brain slices, they showed strong integration, as demonstrated by the projection of neural processes and the migration of neurons across the implant-host boundary. The implanted cells also showed signalling activity, which correlated with that of the host cells. This indicates that the human and mouse cells were communicating with each other, demonstrating functional as well as structural integration.

The researchers now intend to further refine the droplet printing technique to create complex multi-layered cerebral cortex tissues that more realistically mimic the human brain’s architecture. Besides their potential for repairing brain injuries, these engineered tissues might be used in drug evaluation, studies of brain development, and to improve our understanding of the basis of cognition.

The new advance builds on the team’s decade-long track record in inventing and patenting 3D printing technologies for synthetic tissues and cultured cells.

Senior author Dr Linna Zhou (Department of Chemistry, University of Oxford) said: “Our droplet printing technique provides a means to engineer living 3D tissues with desired architectures, which brings us closer to the creation of personalised implantation treatments for brain injury.”

Senior author Associate Professor Francis Szele (Department of Physiology, Anatomy and Genetics, University of Oxford) added: “The use of living brain slices creates a powerful platform for interrogating the utility of 3D printing in brain repair. It is a natural bridge between studying 3D printed cortical column development in vitro and their integration into brains in animal models of injury.”

Senior author Professor Zoltán Molnár (Department of Physiology, Anatomy and Genetics, University of Oxford) said: “Human brain development is a delicate and elaborate process with a complex choreography. It would be naïve to think that we can recreate the entire cellular progression in the laboratory. Nonetheless, our 3D printing project demonstrates substantial progress in controlling the fates and arrangements of human iPSCs to form the basic functional units of the cerebral cortex.”

Source: University of Oxford

Categories : Implants and ProsthesesTags :

UK Man to Receive World’s First 3D-printed Eye

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Photo by Victor Freita on Pexels

A Moorfields Eye Hospital patient in the UK will be the first to benefit solely from a fully digital 3D printed prosthetic eye. Steve Verze, an engineer, will go home from the Old Street hospital with only a printed eye fitted that day. He first tried his eye on November 11 alongside a traditional acrylic prosthetic.

This new 3D printing process avoids the invasive process of making a mould of the eye socket: a procedure so difficult that in children it can require putting them under general anaesthetic.

Steve said: “I’ve needed a prosthetic since I was 20, and I’ve always felt self-conscious about it. When I leave my home I often take a second glance in the mirror, and I’ve not liked what I’ve seen. This new eye looks fantastic and, being based on 3D digital printing technology, it’s only going to be better and better.”

Professor Mandeep Sagoo, consultant ophthalmologist at Moorfields and professor of ophthalmology at the NIHR Biomedical Research Centre at Moorfields Eye Hospital UCL and Institute of Ophthalmology, said: “We are excited about the potential for this fully digital prosthetic eye.

“We hope the forthcoming clinical trial will provide us with robust evidence about the value of this new technology, showing what a difference it makes for patients. It clearly has the potential to reduce waiting lists.”

The printed eye is more realistic, with clearer definition and giving real depth to the pupil. The way light travels through the full depth of the printed eye is more natural than current prosthetics, which simply have the iris hand-painted onto a black disc embedded in the eye, with no light passage through the eye.

The current process can take six weeks but 3D printing halves that time, and the scanning ensures a precise fit. 

Source: Islington Gazette

Categories : Implants and ProsthesesTags :

Innovative 3D Printing Makes Stronger and More Flexible Implants

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Photo by Tom Claes on Unsplash

A new 3D printing process developed by University of Nottingham researchers, allows customised production of artificial body parts and other medical devices with built-in functionality offering shape and durability, while also cutting bacterial infection risk.

“Most mass-produced medical devices fail to completely meet the unique and complex needs of their users,” explained lead researcher Dr Yinfeng He, Centre for Additive Manufacturing. “Similarly, single-material 3D printing methods have design limitations that cannot produce a bespoke device with multiple biological or mechanical functions.”

“But for the first time, using a computer-aided, multi-material 3D-print technique, we demonstrate it is possible to combine complex functions within one customised healthcare device to enhance patient wellbeing.”

The team’s hope is that their new design process can be applied to 3D-print any highly customised medical device.

For example, the method could be adapted to create a single-part prosthetic limb or joint with greater comfort and functionality; or printing customised pills containing multiple drugs – known as polypills – optimised to release their contents in a planned sequence.

What it can do

For this study, the researchers applied a computer algorithm to design and manufacture 3D-printed objects made up of two polymer materials with differing stiffness that also prevent bacterial biofilm build-up. Combining these two materials, they produced an implant with the required strength and flexibility.

Artificial finger joint replacements currently use both silicone and metal parts, offering the wearer a standardised level of dexterity but must be rigid enough to implant into bone. The team 3D-printed a finger joint as a demonstration, which offered these dual requirements in one device, while also being able to customise its size and strength to meet individual patient requirements. They can even make use of intrinsically bacteria-resistant and bio-functional multi-materials, combating infection without extra antibiotics.

A new high-resolution characterisation technique (3D orbitSIMS) was used to 3D-map the chemistry of the print structures and to test the bonding between them throughout the part. This showed that the two materials were intermingling at their interfaces; a sign of good bonding and therefore a stronger device.

The study was carried out by the Centre for Additive Manufacturing (CfAM) and funded by the Engineering and Physical Sciences Research Council. The complete findings are published in Advanced Science, in a paper entitled: ‘Exploiting generative design for 3D printing of bacterial biofilm resistant composite devices’.

Prior to making the technique commercialised, the researchers plan to try out more advanced materials with extra functionalities such as controlling immune responses and promoting stem cell attachment.

Source: University of Nottingham

Journal reference: He, Y., et al. (2021) Exploiting Generative Design for 3D Printing of Bacterial Biofilm Resistant Composite Devices. Advanced Science. doi.org/10.1002/advs.202100249.

Categories : Medical Research & TechnologyTags :

A 3D Printed Hydrogel With Self-healing Capacity

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Much research has focused on hydrogels, polymer-based materials containing large amounts of water, but hydrogels with both self-healing and complex construction have proved elusive until now. 

Hydrogels need to fulfil two key criteria if they are to be effective replacements for organic tissue: the ability to form extremely complex shapes, and to self-heal after sustaining damage. Previously, hydrogels created in the laboratory had either the capability of being 3D printed into complex shapes, or had the ability to self-heal. This research realises the first time these two capabilities had been combined into one material.

The development of these materials may now be easier, and cheaper, thanks to the use of 3D printing: the researchers in the MP4MNT (Materials and Processing for Micro and Nanotechnologies) team of the Department of Applied Science and Technology of the Politecnico di Torino, coordinated by Professor Fabrizio Pirri. The researchers detailed their work in the prestigious journal Nature Communications.

In addition, the hydrogel was created using both commercially available materials and printer, thus making the approach proposed extremely flexible and potentially applicable anywhere, throwing open the door for development in the fields of both biomedicine and soft robotics.

The research was carried out in the context of the HYDROPRINT3D doctoral project, funded by the Compagnia di San Paolo, in the frame of “Joint Research Projects with Top Universities” initiative, by the PhD student Matteo Caprioli, under the supervision of the DISAT researcher Ignazio Roppolo, in collaboration with Professor Magdassi’s research group of the Hebrew University of Jerusalem (Israel).
The researchers used the digital pulsed light to create a semi-interpenetrated structure of polymer strands that, when severed, could rejoin in 12 hours at room temperature with no outside intervention. The restored section retains 72% of its initial strength.

“[For] many years, in the MP4MNT group, a research unit coordinated by Dr Annalisa Chiappone and I, specifically devoted to development of new materials that can be processed using 3D printing activated by light,” said Ignazio Roppolo, Researcher, DISAT. “3D printing is able to offer a synergistic effect between the design of the object and the intrinsic properties of materials, making [it] possible to obtain manufactured items with unique features.

“From our perspective, we need to take advantage of this synergy to best develop the capabilities of 3D printing, so that this can truly become an element of our everyday life. And this research falls right in line with this philosophy.”

This research represents a first step towards the development of highly complex devices, which can exploit both the complex geometries and the intrinsic self-healing properties in various application fields. Once biocompatibility studies have been refined, it will be possible to use these structures both for cellular mechanism research and for regenerative medicine applications.

Source: News-Medical.Net

Journal reference: Caprioli, M., et al. (2021) 3D-printed self-healing hydrogels via Digital Light Processing. Nature Communications. doi.org/10.1038/s41467-021-22802-z.