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Scientists invent ultra-thin, minimally-invasive pacemaker controlled by light

Ultralight membrane can regulate heartbeats with the aid of an optic fiber

Sometimes our bodies need a boost. Millions of Americans rely on pacemakers—small devices that regulate the electrical impulses of the heart in order to keep it beating smoothly. But to reduce complications, researchers would like to make these devices even smaller and less intrusive.

A team of researchers with the University of Chicago has developed a wireless device, powered by light, that can be implanted to regulate cardiovascular or neural activity in the body. The featherlight membranes, thinner than a human hair, can be inserted with minimally invasive surgery and contain no moving parts.

Published Feb. 21 in Nature, the results could help reduce complications in heart surgery and offer new horizons for future devices.

“The early experiments have been very successful, and we’re really hopeful about the future for this translational technology,” said Pengju Li, a graduate student at the University of Chicago Pritzker School of Molecular Engineering and first author on the paper.

‘A new frontier’

The laboratory of Prof. Bozhi Tian has been developing devices for years that can use technology similar to solar cells to stimulate the body. Photovoltaics are attractive for this purpose because they do not have moving parts or wires that can break down or become intrusive—especially useful in delicate tissues like the heart. And instead of a battery, researchers simply implant a tiny optic fiber alongside to provide power.

But for the best results, the scientists had to tweak the system to work for biological purposes, rather than how solar cells are usually designed.

“In a solar cell, you want to collect as much sunlight as possible and move that energy along the cell no matter what part of the panel is struck,” explained Li. “But for this application, you want to be able to shine a light at a very localized area and activate only that one area.”

For example, a common heart therapy is known as cardiac resynchronization therapy, where different parts of the heart are brought back into sync with precisely timed charges. In current therapies, that’s achieved with wires, which can have their own complications.

Li and the team set out to create a photovoltaic material that would only activate exactly where the light struck.

The eventual design they settled on has two layers of a silicon material known as P-type, which respond to light by creating electrical charge. The top layer has many tiny holes—a condition known as nanoporosity—which boost the electrical performance and concentrate electricity without allowing it to spread.

The result is a miniscule, flexible membrane, which can be inserted into the body via a tiny tube along with an optic fiber—a minimally invasive surgery. The optic fiber lights up in a precise pattern, which the membrane picks up and turns into electrical impulses.

The membrane is just a single micrometer thin—about 100 times smaller than the finest human hair—and a few centimeters square. It weighs less than one fiftieth of a gram; significantly less than current state-of-the-art pacemakers, which weigh at least five grams. “The more lightweight a device is, the more comfortable it typically is for patients,” said Li.

This particular version of the device is meant for temporary use. Instead of another invasive surgery to remove the pacemaker, it simply dissolves over time into a nontoxic compound known as silicic acid. However, the researchers said that the devices could be engineered to last to different desired lifespans, depending on how long the heart stimulation is desired.

“This advancement is a game-changer in cardiac resynchronization therapy,” said Narutoshi Hibino, professor of surgery at the University of Chicago Medicine and co-corresponding author on the study. “We’re at the cusp of a new frontier where bioelectronics can seamlessly integrate with the body’s natural functions.”

Light use

Though the first trials were conducted with heart tissue, the team said the approach could be used for neuromodulation as well—stimulating nerves in movement disorders like Parkinson’s, for example, or to treat chronic pain or other disorders. Li coined the term ‘photoelectroceuticals’ for the field.

Tian said the day when they first tried the pacemaker in trials with pig hearts, which are very similar to those of humans, remains vivid in his memory. “I remember that day because it worked in the very first trial,” he said. “It’s both a miraculous achievement and a reward for our extensive efforts.”

A screening method developed by Li to map the photoelectrochemical output of various silicon-based materials could also have uses elsewhere, Tian pointed out, such as in fields like new battery technologies, catalysts, or photovoltaic cells.

The research team is currently working with the UChicago Polsky Center for Entrepreneurship and Innovation to commercialize the device.

The other UChicago authors on the paper were Jing Zhang, Hidenori Hayashi, Jiping Yue, Wen Li, Chuanwang Yang, Changxu Sun, Jiuyun Shi, and Judah Huberman-Shlaes. The research made us of the Pritzker Nanofabrication Facility at the UChicago Pritzker School of Molecular Engineering and the Electron Microscopy Service of the University of Illinois Chicago Research Resources Center.

Citation: “Monolithic silicon for high spatiotemporal translational photostimulation.” Li et al, Nature, Feb. 21, 2024.

Funding: National Institutes of Health, U.S. Air Force Office of Scientific Research, National Science Foundation, U.S. Army Research Office.

Innovative chemotherapy approach shows promise against lung cancer

Method uses patient’s own cells as trojan horse to direct cancer-killing drugs to tumors

Lung cancer is not the most common form of cancer, but it is by far the deadliest.

Despite treatments such as surgery, radiation therapy and chemotherapy, only about a quarter of all people with the disease will live more than five years after diagnosis, and lung cancer kills more than 1.8 million people worldwide each year, according to the World Health Organization.

To improve the odds for patients with lung cancer, researchers from The University of Texas at Arlington and UT Southwestern Medical Center have pioneered a novel approach to deliver cancer-killing drugs directly into cancer cells.

“Our method uses the patient’s own cellular material as a trojan horse to transport a targeted drug payload directly to the lung cancer cells,” said Kytai T. Nguyen, lead author of a new study on the technique in the peer-reviewed Bioactive Materials and the Alfred R. and Janet H. Potvin Distinguished Professor in Bioengineering at UTA. “The process involves isolating T-cells (a type of immune cell) from the cancer patient and modifying them to express a specific receptor that targets the cancer cells.”

The crucial step in this new technique involves isolating the cell membrane from these modified T-cells, loading the membranes with chemotherapy medications, and then coating them onto tiny drug-delivery granules. These nanoparticles are roughly 1/100 the size of a strand of hair.

When these membrane-coated nanoparticles are injected back into the patient, the cell membrane acts as a guide, directing the nanoparticles to the tumor cells with precision. This approach is designed to deceive the patient’s immune system, as the coated nanoparticles mimic the properties of immune cells, avoiding detection and clearance by the body.

“The key advantage of this method lies in its highly targeted nature, which allows it to overcome the limitations of conventional chemotherapy that often lead to detrimental side effects and reduced quality of life for patients,” said co-author Jon Weidanz, associate vice president for research and innovation and a researcher in kinesiology and bioengineering.

“By delivering chemotherapy directly to the tumor cells, the system aims to minimize collateral damage to healthy tissues,” continued Weidanz, who also is a member of UTA’s Multi-Interprofessional Center for Health Informatics.

In the study, researchers loaded the nanoparticles with the anti-cancer drug Cisplatin. The membrane-coated nanoparticles accumulated in parts of the body with the tumors rather than in other parts of the body. As a result, this targeted delivery system was able to reduce the size of the tumors in the control group, demonstrating its efficacy.

“This personalized approach could pave the way for a new era of medicine tailored to each patient’s unique characteristics and the specific nature of their tumor,” Nguyen said. “The potential for reduced side effects and improved effectiveness makes our technique a noteworthy advancement in the field of cancer treatment.”

Nguyen’s work was supported by a $250,000 grant from the Cancer Prevention and Research Institute of Texas.

Assessing the efficacy and viability of artificial skin in patients with severe burns

Research team presented their follow-up and histological analysis of the first 12 patients treated

Original Source: Medical Xpress

UGR scientists have demonstrated the efficacy and viability of the artificial skin UGRSKIN, an advanced therapy medicinal product (ATMP) they developed in 2012, which has proven to be highly beneficial in the treatment of patients with major burns. Moreover, it does not cause any side effects or significant complications.

The Tissue Engineering Research Group of the Department of Histology at the UGR’s Faculty of Medicine and the Biohealth Research Institute in Granada—a pioneering group in the design and manufacture of artificial human tissues—invented and unveiled an artificial skin model called UGRSKIN in 2012. The model is based on  and natural biomaterials developed by the research group.

The research team was able to demonstrate the efficacy of the skin model in laboratory animals and develop all the quality controls necessary for its characterization, in accordance with the requirements of the relevant regulatory agencies.

Subsequently, having demonstrated the potential usefulness of the UGRSKIN model, the UGR team, in close collaboration with the Regional Government of Andalusia’s Network for Design and Translation of Advanced Therapies (RAdytTA), was able to manufacture this pharmaceutical-grade artificial skin for use as an advanced therapy medicinal product (ATMP), in accordance with the regulations of the Spanish Agency of Medicines and Medical Devices (AEMPS) and existing European quality standards.

Following its approval by the AEMPS, UGRSKIN was used for the first time in 2016 to treat a patient with severe burns on 70% of their body at the leading burn unit in Andalusia, located at the Virgen del Rocío University Hospital in Seville, with good results. Since then, a total of 15 patients (eight adults and four children) have been treated, with an overall survival rate of almost 80%.

At a press conference held at the UGR’s Faculty of Medicine, where the artificial skin was designed, the research team presented their follow-up and histological analysis of the first 12 patients treated with UGRSKIN. These results led to the research article “Histological assessment of nanostructured fibrin-agarose skin substitutes grafted in burnt patients. A time-course study,” published in Bioengineering & Translational Medicine.

“Once implanted, the UGRSKIN model quickly fused with the patient’s tissue and almost immediately formed an epidermis very similar to the normal human epidermis, thus helping to protect the patient from possible external pathogens. In addition, two months after implantation, the dermis of the implanted tissue was able to progressively remodel itself until it became histologically similar to the normal dermis,” explains Professor Miguel Alaminos.

Treating patients with  is a major health care challenge. Despite the advances of modern medicine, the survival rate of patients with deep burns over large areas of the body is still very low. It is therefore necessary to develop new, truly effective treatments for these cases, such as the artificial skin developed at the UGR.

The preliminary results of the project presented at the UGR have been announced at international forums in Berlin, Zurich, Nantes and Shanghai. As a result of this breakthrough, the next meeting of the European Skin Tissue Engineering Network for Major Burns will be organized in Granada in June 2024 by the Tissue Engineering Research Group.

The patients treated with the UGRSKIN artificial skin have experienced an improvement in their quality of life, and some have even managed to overcome challenges and difficulties, such as climbing high mountains and participating in demanding sports competitions.

The UGR press conference (which was chaired by the Rector of the UGR, Pedro Mercado) was attended by Álvaro Trigo Puig, one of the patients who received the artificial skin implant in 2018.

Álvaro is a 28-year-old from Madrid who suffered burns to 63% of his skin in a serious fire in 2018. His injuries left him in a coma for 10 days and he spent four months in the Virgen del Rocío University Hospital in Seville.

Since receiving the artificial skin implant designed at the UGR, Álvaro Trigo has organized and carried out long-distance sports events for charity. Among other feats, he has climbed Mount Kilimanjaro and Mont Blanc, and swum across the Strait of Gibraltar, between Formentera and Ibiza, and from the Cíes Islands to Vigo (Galicia) with his feet chained together.

 

More information: Miguel Angel Martin‐Piedra et al, Histological assessment of nanostructured fibrin‐agarose skin substitutes grafted in burnt patients. A time‐course study, Bioengineering & Translational Medicine (2023). DOI: 10.1002/btm2.10572

Can hydrogels help mend a broken heart?

Researchers design gel from wood pulp to heal damaged heart tissue and improve cancer treatments

Original Source: University of Waterloo

You can mend a broken heart now that researchers invented a new hydrogel that can be used to heal damaged heart tissue and improve cancer treatments.

University of Waterloo chemical engineering researcher Dr. Elisabeth Prince teamed up with researchers from the University of Toronto and Duke University to design the synthetic material made using cellulose nanocrystals, which are derived from wood pulp. The material is engineered to replicate the fibrous nanostructures and properties of human tissues, thereby recreating its unique biomechanical properties.

“Cancer is a diverse disease and two patients with the same type of cancer will often respond to the same treatment in very different ways,” Prince said. “Tumour organoids are essentially a miniaturized version of an individual patient’s tumour that can be used for drug testing, which could allow researchers to develop personalized therapies for a specific patient.”

As director of the Prince Polymer Materials Lab, Prince designs synthetic biomimetic hydrogels for biomedical applications. The hydrogels have a nanofibrous architecture with large pores for nutrient and waste transport, which affect mechanical properties and cell interaction.

Prince, a professor in Waterloo’s Department of Chemical Engineering, utilized these human-tissue mimetic hydrogels to promote the growth of small-scale tumour replicas derived from donated tumour tissue.

She aims to test the effectiveness of cancer treatments on the mini-tumour organoids before administering the treatment to patients, potentially allowing for personalized cancer therapies. This research was conducted alongside Professor David Cescon at the Princess Margaret Cancer Center.

Prince’s research group at Waterloo is developing similar biomimetic hydrogels to be injectable for drug delivery and regenerative medical applications as Waterloo researchers continue to lead health innovation in Canada.

Her research aims to use injected filamentous hydrogel material to regrow heart tissue damaged after a heart attack. She used nanofibers as a scaffolding for the regrowth and healing of damaged heart tissue.

“We are building on the work that I started during my PhD to design human-tissue mimetic hydrogels that can be injected into the human body to deliver therapeutics and repair the damage caused to the heart when a patient suffers a heart attack,” Prince said.

Prince’s research is unique as most gels currently used in tissue engineering or 3D cell culture don’t possess this nanofibrous architecture. Prince’s group uses nanoparticles and polymers as building blocks for materials and develops chemistry for nanostructures that accurately mimic human tissues.

The next step in Prince’s research is to use conductive nanoparticles to make electrically conductive nanofibrous gels that can be used to heal heart and skeletal muscle tissue.

The research was recently published in the journal Proceedings of the National Academy of Sciences.

Researchers find new way to deliver treatment to infants at risk of cerebral palsy

Drug-release technology carries medication to the site of perinatal brain injury, protecting infants from harmful side-effects.

Delivering critical early-life medication to newborns at risk of cerebral palsy from suspected brain injury will be safer thanks to a University of Alberta research team.

Doctors have long known that brain injury during labour and delivery is a leading cause of cerebral palsy, a group of conditions affecting movement and posture, but they’ve had little ability to help their tiny patients. In addition to lacking diagnostic tools to confirm the presence of a brain injury, doctors have had few interventions at their disposal.

“It’s a dual effect,” says Larry Unsworth, a professor of biomedical engineering and member of the Women and Children’s Health Research Institute.

One kind of perinatal brain injury caused by oxygen deprivation, hypoxic-ischemic encephalopathy (HIE), is sometimes treated with therapeutic hypothermia, in which the infant’s body is cooled to slow the metabolism of brain cells and stop further damage from occurring. Unfortunately, this approach has been shown to be ineffective in treating moderate to severe HIE.

With support from the Stollery Children’s Hospital Foundation through WCHRI, Unsworth set out to find a solution to this problem alongside pediatrics professor Jerome Yager and research team members Jung-Lynn Jonathan Yang, Rukhmani Narayanamurthy and Ed Armstrong.

“We wondered if there was a way to target the change in the local brain tissue caused by HIE to reduce damage in the brain,” says Unsworth. “Easy question to ask, hard to do.”

The team realized the answer might lie in finding a safer way to deliver anti-inflammatory medications, which could augment the effects of therapeutic hypothermia. The drugs come with known health risks, but Unsworth and the team wondered whether there was a way to transport the medication to the site of the brain injury and minimize damaging other organs along the way.

“So that’s what we did — we developed a self-assembled, peptide system that could carry dexamethasone (a corticosteroid) to the site of injury in the brain,” he said.

The key to the system’s effectiveness is cooling only the infant’s head while keeping the body at normal temperature. Molecules of the drug are not activated until they move through the body and past the blood-brain barrier into the cooler temperatures of the brain. Because the protein delivery system administers such a small amount of the drug, it is also safe to give preventatively.

“The key was to enable immediate therapeutic access to the newborn’s brain as early as possible after birth and during brain hypothermia, which is standard of care across all neonatal intensive care units,” says Yager.

Unsworth and his colleagues are now pursuing additional funding to continue developing the technology so it can be commercialized and put into the hands of doctors.

“Targeted treatment to these injured cells could dramatically improve the outcomes of children who suffer from this condition,” he says.

 

More information: Rukhmani Narayanamurthy et al, Administration of selective brain hypothermia using a simple cooling device in neonatal rats, Journal of Neuroscience Methods (2023). DOI: 10.1016/j.jneumeth.2023.109838

Artificial oral mucosa as a model for testing dental biomaterials?

A new study suggests that lab-grown oral mucosa can successfully be used for testing biological effects of dental materials.

Original Source: University of Oslo

A new study suggests that lab-grown oral mucosa can successfully be used for testing biological effects of dental materials. The project is a collaboration between the Institute of Oral Biology (IOB) and the Nordic Institute of Dental Materials (NIOM) and is published in Biomaterial Investigations in Dentistry.

The oral cavity is continuously exposed to a range of chemical substances released from dental materials used in dental fillings and prostheses. Since these materials will be in the mouth for a longer period, it is important that dental materials are safe and do not cause adverse effects on structures in the oral cavity, including the oral mucosa. Therefore, investigation of biological effects of dental materials using suitable laboratory model systems is crucial in the development and/or refinement of dental materials. In this regard, single-cell cultures (epithelial cells, fibroblasts) derived from oral mucosa and grown as a two-dimensional (2D) culture have been widely used for this purpose.

3D models that mimic the structure of oral mucosa

As oral mucosa is a complex three-dimensional (3D) structure consisting of various cell types, using 2D model systems is inadequate to understand the cellular processes dependent on cell-cell interactions between different cell types and to obtain clinically relevant biological effects of dental materials. In this context, in vitro, 3D models consisting of different cell types are gaining popularity in life science research. We have successfully used 3D models consisting of normal oral keratinocytes (NOK) and cancerous keratinocytes grown on top of a collagen matrix consisting of normal oral fibroblasts (NOF), thereby mimicking normal oral and cancerous oral epithelium (Figure 1A). We have previously used these models to examine

  • i) proliferation, differentiation, and invasion and of tumor cells (Sapkota D, BMC Cancer, 2015; Toközlü SB, Eur J Oral Sciences, 2023) (Figure 1B), and
  • ii) interaction between bacteria and oral epithelium (Dabija-Wolter G, Arc Oral Biol, 2012).

Investigating the biological effects using 3D models

In the current study, a collaborative project between the Institute of Oral Biology (IOB) and the Nordic Institute of Dental Materials (NIOM) recently published in Biomaterial Investigations in Dentistry, we have investigated the biological effects of 2-hydroxethyl methacrylate (HEMA), a major constituent of dental resins, on laboratory engineered 3D-organotypic models of oral mucosa. The 3D models were created by co-culturing NOK on top of a collagen I matrix consisting of NOF. Using several analysis methods (morphometric/histological analysis, qRT-PCR, immunohistochemistry), the treatment of 3D models consisting of OEC and NOF was found to increase apoptosis of NOK. Besides, HEMA treatment was found to increase autophagy flux in NOK as indicated by the expression of SQSTM1 mRNA and corresponding protein levels (Figure 1C). These results indicate that 3D-organotypic co-cultures of NOK represent a biologically relevant model system for investigating the biological effects of HEMA and other dental biomaterials.

Nevertheless, establishing and maintaining NOK culture is expensive and difficult, as NOKs tend to differentiate after a limited number of passages in 2D cultures. Hence, we investigated the possible use of oral cancer cells as an alternative to NOK for 3D models. Our results indicated that 3D-co-cultures of NOK and oral cancer cells reacted similarly to HEMA treatment with respect to cell proliferation and activation of autophagy flux. These observations open the possibility for the use of 3D models based on oral cancer cells as an easier and cheaper model system for testing biological effects of dental materials.

These models are flexible with respect to the cell types, timepoint, and duration of treatment and offer a wide range of downstream analysis possibilities (morphometric/histological analysis, global and pathway-focused molecular analysis) using the artificial tissue or culture medium.

References

Dabija-Wolter G, Sapkota D, Cimpan MR, Neppelberg E, Bakken V, Costea DE. Limited in-depth invasion of Fusobacterium nucleatum into in vitro reconstructed human gingiva. Arch Oral Biol. 2012

Sapkota D, Bruland O, Parajuli H, Osman TA, Teh MT, Johannessen AC, Costea DE. S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC Cancer. 2015

Sharma S, Khan Q, Schreurs OJF, Sapkota D, Samuelsen JT. Investigation of biological effects of HEMA in 3D-organotypic co-culture models of normal and malignant oral keratinocytes. Biomater Investig Dent. 2023

Toközlü SB, D. Sapkota, E. M. Vallenari, O. Schreurs, T. M. Søland. Cortactin expression in a Norwegian cohort of human papillomavirus negative oral squamous cell carcinomas of the mobile tongue. Eur J Oral Sciences. 2023

New AI tool discovers realistic ‘metamaterials’ with unusual properties

A coating that can hide objects in plain sight, or an implant that behaves exactly like bone tissue. These extraordinary objects are already made from ‘metamaterials’.

A coating that can hide objects in plain sight, or an implant that behaves exactly like bone tissue. These extraordinary objects are already made from ‘metamaterials’. Researchers from TU Delft have now developed an AI tool that not only can discover such extraordinary materials but also makes them fabrication-ready and durable. This makes it possible to create devices with unprecedented functionalities. They publish their findings in Advanced Materials.

The properties of normal materials, such as stiffness and flexibility, are determined by the molecular composition of the material, but the properties of metamaterials are determined by the geometry of the structure from which they are built. Researchers design these structures digitally and then have it 3D-printed. The resulting metamaterials can exhibit unnatural and extreme properties. Researchers have, for instance, designed metamaterials that, despite being solid, behave like a fluid.

“Traditionally, designers use the materials available to them to design a new device or a machine. The problem with that is that the range of available material properties is limited. Some properties that we would like to have, just don’t exist in nature. Our approach is: tell us what you want to have as properties and we engineer an appropriate material with those properties. What you will then get, is not really a material but something in-between a structure and a material, a metamaterial”, says professor Amir Zadpoor of the Department of Biomechanical Engineering.

Inverse design

Such a material discovery process requires solving a so-called inverse problem: the problem of finding the geometry that gives rise to the properties you desire. Inverse problems are notoriously difficult to solve, which is where AI comes into the picture. TU Delft researchers have developed deep learning models that solve these inverse problems.

“Even when inverse problems were solved in the past, they have been limited by the simplifying assumption that the small-scale geometry can be made from an infinite number of building blocks. The problem with that assumption is that metamaterials are usually made by 3D-printing and real 3D-printers have a limited resolution, which limits the number of building blocks that fit within a given device”, says first author Dr. Helda Pahlavani.

The AI models developed by TU Delft researchers break new ground by bypassing any such simplifying assumptions. “So we can now simply ask: how many building blocks does your manufacturing technique allow you to accommodate in your device? The model then finds the geometry that gives you your desired properties for the number of building blocks that you can actually manufacture.”

Unlocking full potential

A major practical problem neglected in previous research, has been the durability of metamaterials. Most existing designs break once they are used a few times. That is because existing metamaterials design approaches do not take durability into account. “So far, it has been only about what properties can be achieved. Our study considers durability and selects the most durable designs from a large pool of design candidates. This makes our designs really practical and not just theoretical adventures,” says Zadpoor.

The possibilities of metamaterials seem endless, but the full potential is far from being realised, says assistant professor Mohammad J. Mirzaali, corresponding author of the publication. This is because finding the optimal design of a metamaterial is currently still largely based on intuition, involves trial and error and is therefore labour-intensive. Using an inverse design process, where the desired properties are the starting point of the design, is still very rare within the metamaterials field. “But we think the step we have taken, is revolutionary in the field of metamaterials. It could lead to all kinds of new applications.” There are possible applications in orthopaedic implants, surgical instruments, soft robots, adaptive mirrors, and exo-suits.

New understanding of avian eggshell attachment

Implications for medical procedures and egg industry

Original Source: McGill University

Athletes often suffer injuries to ligaments in their knees, particularly to the anterior cruciate ligament or ACL. While surgery to replace these torn ligaments is becoming increasingly common around the world it often needs to be repeated. That’s because it has proved challenging to anchor fibrous, soft and wet ligament grafting material into hard bone.

Now, McGill University researchers have new information from the eggshell membrane in chicken eggs that could help change this picture thanks to the potential it offers for improvements in tissue engineering and biomaterial grafts.

Their findings also have the potential to reduce losses for commercial egg and poultry producers.

Anchoring soft and wet fibres by “nailing” them in place 

The researchers discovered how the hard shell of a bird egg attaches to the underlying wet fibrous membrane of the egg (the thin membranous layer found inside the shell seen when peeling a hard-boiled egg). By using advanced 3D imaging X-ray and electron microscopes together with cryo-preservation methods the research team were able to peer into this interface in three dimensions to visualize and quantify the interlocking phenomenon.

“Until now, no one had considered how this interface between these two very dissimilar substances, one a hard biorock, and the other a soft fibrous membrane, might be secured at the nanoscale,” says Marc McKee, a professor in the Faculty of Dental Medicine and Oral Health Sciences, and in the Department of Anatomy and Cell Biology, and the principal investigator of the study conducted by doctoral student Daniel Buss and published recently in iScience. “What we found about this soft-hard interface is quite remarkable.”

Nanospikes increase the surface area of contact between soft and hard materials and ensure food safety 

The McGill team discovered that, at a certain stage in the development of an egg prior to laying, the shell sends mineral nanospikes into the soft and compliant surface fibres of the underlying eggshell membrane. This membrane surrounds the soft contents of the egg interior, being either the egg white and yolk from table eggs, or the developing chick embryo in a fertilized and incubated egg.

This nanospiking attachment process between two highly dissimilar materials substantially increases the surface area of the interface between the soft and wet organic fibres and the hard and largely dry inorganic mineral. Such an attachment importantly anchors and secures this soft-hard interface to prevent slipping and sliding of the fibres within the shell.

Otherwise, detachment of the membrane from the shell can be lethal for the embryonic chick, can weaken the shell, and/or can allow the invasion of pathogens (such as salmonella) into the interior contents of the egg. Food safety of the table egg relies on an intact shell that is well-integrated with its underlying membrane.

Implications for medical procedures and commercial egg production 

With this new understanding of the shell-membrane interface as being a characteristic feature of strong, safe and healthy eggs, losses for table egg producers and poultry breeders might be reduced through the establishment of commercial genetic breeding programs that maintain or maximize this interfacial structure.

The findings might also potentially lead to new engineered, hybrid composite material designs, and to new procedures to improve the outcomes of various medical and dental reconstructive surgeries, both of which may require attaching soft wet fibres to hard materials.

About the study

“Attaching organic fibers to mineral: The case of the avian eggshell” by Daniel J. Buss , Natalie Reznikov , Marc D. McKee was published in iScience

Promising development for breast cancer patients

Researchers have developed a novel monoclonal antibody which specifically targets a certain type of breast cancer cell

Original Source: Tohoku University

In a step forward for breast cancer treatment, researchers at Tohoku University have developed a novel monoclonal antibody which specifically targets a certain type of breast cancer cell. Their findings, published in the International Journal of Molecular Sciences, offer a new tool for treating this disease.

Breast cancer remains a significant global health concern that afflicts millions of people each year. The HER2-positive subtype of breast cancer is one of the most aggressive and challenging to treat. Approximately 20% of breast cancer cases are classified as HER2-positive, meaning that there is an urgent need for therapies targeted to this specific subtype.

A research team led by Yukinari Kato rose to this challenge by developing a monoclonal antibody that precisely targets HER2-positive breast cancer cells. Monoclonal antibodies are specialized proteins engineered to recognize and bind to specific targets with exceptional precision.

HER2-positive breast cancer cells have more of the HER2 protein on their surface than healthy cells. This protein plays an important role in cell growth and division, and the excess of HER2 is one reason HER2-positive tumors are aggressive. By specifically targeting HER2-positive cells, the antibody disrupts their growth and proliferation while minimizing harm to surrounding healthy tissue.

“The development of this antibody represents a significant milestone in our ongoing efforts to advance breast cancer treatment,” says Kato. “By targeting HER2-positive breast cancer cells with precision, we can offer patients a more effective and less toxic treatment option.”

The new antibody offers a more targeted and selective approach than conventional treatments, such as chemotherapy, which can cause significant collateral damage to healthy cells. This precision not only enhances the efficacy of treatment but also reduces the incidence and severity of side effects, greatly improving the quality of life of breast cancer patients.

The project is set to move to the next phase, which will include clinical trials and regulatory approval processes. The researchers will also explore potential applications of other novel antibodies in various therapeutic areas, assessing whether they can improve outcomes for people battling other types of cancer.

The research was supported by grants from the Japan Agency for Medical Research and Development (AMED), including the “Science and Technology Platform Program for Advanced Biological Medicine” and “Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)”.

 

Publication Details:
Title: A Cancer-specific Monoclonal Antibody against HER2 Exerts Antitumor Activities in Human Breast Cancer Xenograft Models
Authors: Mika K. Kaneko, Hiroyuki Suzuki, Tomokazu Ohishi, Takuro Nakamura, Tomohiro Tanaka, and Yukinari Kato
Journal: International Journal of Molecular Sciences
DOI: 10.3390/ijms25031941

Artificial cartilage with the help of 3D printing

A new approach to producing artificial tissue has been developed at TU Wien: Cells are grown in microstructures created in a 3D printer.

Is it possible to grow tissue in the laboratory, for example to replace injured cartilage? At TU Wien (Vienna), an important step has now been taken towards creating replacement tissue in the lab – using a technique that differs significantly from other methods used around the world.

A special high-resolution 3D printing process is used to create tiny, porous spheres made of biocompatible and degradable plastic, which are then colonized with cells. These spheroids can then be arranged in any geometry, and the cells of the different units combine seamlessly to form a uniform, living tissue. Cartilage tissue, with which the concept has now been demonstrated at TU Wien, was previously considered particularly challenging in this respect.

Tiny spherical cages as a scaffold for the cells

“Cultivating cartilage cells from stem cells is not the biggest challenge. The main problem is that you usually have little control over the shape of the resulting tissue,” says Oliver Kopinski-Grünwald from the Institute of Materials Science and Technology at TU Wien, one of the authors of the current study. “This is also due to the fact that such stem cell clumps change their shape over time and often shrink.”

To prevent this, the research team at TU Wien is working with a new approach: specially developed laser-based high-resolution 3D printing systems are used to create tiny cage-like structures that look like mini footballs and have a diameter of just a third of a millimeter. They serve as a support structure and form compact building blocks that can then be assembled into any shape.

Stem cells are first introduced into these football-shaped mini-cages, which quickly fill the tiny volume completely. “In this way, we can reliably produce tissue elements in which the cells are evenly distributed and the cell density is very high. This would not have been possible with previous approaches,” explains Prof. Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at TU Wien.

Growing together perfectly

The team used differentiated stem cells – i.e. stem cells that can no longer develop into any type of tissue, but are already predetermined to form a specific type of tissue, in this case cartilage tissue. Such cells are particularly interesting for medical applications, but the construction of larger tissue is challenging when it comes to cartilage cells. In cartilage tissue, the cells form a very pronounced extracellular matrix, a mesh-like structure between the cells that often prevents different cell spheroids from growing together in the desired way.

If the 3D-printed porous spheroids are colonized with cells in the desired way, the spheroids can be arranged in any desired shape. The crucial question is now: do the cells of different spheroids also combine to form a uniform, homogeneous tissue?

“This is exactly what we have now been able to show for the first time,” says Kopinski-Grünwald. “Under the microscope, you can see very clearly: neighboring spheroids grow together, the cells migrate from one spheroid to the other and vice versa, they connect seamlessly and result in a closed structure without any cavities – in contrast to other methods that have been used so far, in which visible interfaces remain between neighboring cell clumps.”

The tiny 3D-printed scaffolds give the overall structure mechanical stability while the tissue continues to mature. Over a period of a few months, the plastic structures degrade, they simply disappear, leaving behind the finished tissue in the desired shape.

First step towards medical application

In principle, the new approach is not limited to cartilage tissue, it could also be used to tailor different kinds of larger tissues such as bone tissue. However, there are still a few tasks to be solved along the way – after all, unlike in cartilage tissue, blood vessels would also have to be incorporated for these tissues above a certain size.

“An initial goal would be to produce small, tailor-made pieces of cartilage tissue that can be inserted into existing cartilage material after an injury,” says Oliver Kopinski-Grünwald. “In any case, we have now been able to show that our method for producing cartilage tissue using spherical micro-scaffolds works in principle and has decisive advantages over other technologies.”

Original publication

O. Kopinski-Grünwald et al., Scaffolded spheroids as building blocks for bottom-up cartilage tissue engineering show enhanced bioassembly dynamics, Acta Biomaterialia, 174, 163 (2024).