Radiation is a powerful tool for treating cancer, but prolonged exposure can damage the skin. Radiation-induced skin injuries are painful and increase a person’s chances of infection and long-term inflammation. Now, researchers in ACS Biomaterials Science & Engineering report an aspirin-containing hydrogel that mimics the nutrient-rich fluid between cells and accelerates healing of skin damaged by radiation in animals. With further development, the new salve could provide effective and rapid wound healing for humans.
Most people undergoing radiotherapy for cancer will experience radiation-induced skin injury that can include redness, pain, ulcers, necrosis and infection. There are few treatments for these wounds, with the most common methods being debridement and hyperbaric oxygenation. Wound dressings made from hydrogels are gaining popularity because they are easy to apply and provide a wet environment for healing that is similar to the inside of the body. Glycopeptide-based hydrogels are especially promising: In laboratory and animal studies, the nanofibre structures have promoted cellular growth and regulated cell adhesion and migration. A research team led by Jiamin Zhang, Wei Wang, Yumin Zhang and Jianfeng Liu proposed loading aspirin, a common anti-inflammatory drug, into a glycopeptide-based hydrogel to create a multifunctional wound dressing for radiation-induced skin injuries.
In lab tests with cultured cells, the researchers found that the aspirin-contained hydrogel scavenged reactive oxygen species, repaired DNA double-strand breaks and inhibited inflammation caused by radiation exposure without affecting cellular growth. In mouse models of radiation-induced skin injury, the researchers found that dressing wounds for three weeks with the salve reduced acute injuries and accelerated healing – results that the team says point to its potential as an easy-to-administer, on-demand treatment option for reducing radiation damage and promoting healing in humans.
Scanning electron micrograph of red blood cells, T cells (orange) and platelets (green). Source: Wikimedia CC0
Researchers have developed hydrogel-based synthetic platelets that can be used to stop bleeding and, in animal models, has been shown to enhance healing at an injury site. The research is presented in Science Translational Medicine.
A number of medical situations require platelet transfusions – such as cases of severe bleeding, or for patients who are going into surgery or receiving chemotherapy. Currently, patients in any of those situations receive platelets harvested from blood donors, ideally from donors with a compatible blood type. This is challenging, because there is a very limited supply of platelets available, those platelets have a limited shelf life, and the platelets must be stored under controlled conditions.
“We’ve developed synthetic platelets that can be used with patients of any blood type and are engineered to go directly to the site of injury and promote healing,” says Ashley Brown, corresponding author of a paper on the synthetic platelets and biomedical engineering programme. “The synthetic platelets are also easy to store and transport, making it possible to give the synthetic platelets to patients in clinical situations sooner – such as in an ambulance or on the battlefield.”
The synthetic platelets are made of hydrogel nanoparticles that mimic the size, shape and mechanical properties of human platelets. Hydrogels are water-based gels that are composed of water and a small proportion of polymer molecules.
“Our synthetic platelets are deformable – meaning they can change shape – in the same way that normal platelets are,” Brown explains.
The researchers engineered the surface of the synthetic platelets to incorporate antibody fragments that bind to a protein called fibrin. When a body is injured, it synthesises fibrin at the site of the wound. The fibrin then forms a mesh-like substance to promote clotting.
“Because the synthetic platelets are coated with these antibody fragments, the synthetic platelets travel freely through the blood stream until they reach the wound site,” Brown says. “Once there, the antibody fragments bind to the fibrin, and the synthetic platelets expedite the clotting process.”
In addition to forming a clot within the fibrin network, the synthetic platelets act to contract the clot over time – just like normal platelets.
“This expedites the process of healing, allowing the body to move forward with tissue repair and recovery,” Brown says.
The researchers initially demonstrated the efficacy of the antibody fragments via in vitro testing, as well as demonstrating that the antibody fragments and synthetic platelets could be produced at scales that would make them viable for large-scale manufacturing.
The researchers then used a mouse model to determine the optimal dose of synthetic platelets necessary to stop bleeding.
Subsequent research in both mouse and pig models demonstrated that the synthetic platelets travelled to the site of a wound, expedited clotting, did not cause any clotting problems in areas outside of the wound, and accelerated healing.
“In the mouse and pig models, healing rates were comparable in animals that received platelet transfusions and synthetic platelet transfusions,” Brown says. “And both groups fared better than animals that did not receive either transfusion. We also found that the animals in both mouse and pig models were able to safely clear the synthetic platelets over time through normal kidney function. We didn’t see any adverse health effects associated with the use of the synthetic platelets.
“In addition, based on our preliminary estimates, we anticipate that the cost of the synthetic platelets – if they are approved for clinical use – would be comparable to the current cost of platelets,” Brown says.
“We are wrapping up preclinical efficacy testing and are in the process of securing funding for preclinical safety work that should allow us to obtain FDA approval to begin clinical trials within two years.”
A breakthrough study sets the foundation of a ground-breaking treatment regimen for treating ventricular arrhythmia. The study, published in Nature Communications, demonstrates the design and feasibility of a new hydrogel-based pacing modality.
The urgent need for an effective therapeutic regimen for ventricular arrhythmia inspired a team led by Dr. Mehdi Razavi at The Texas Heart Institute (THI), to collaborate The University of Texas at Austin (UT Austin) Cockrell School of Engineering led by Dr. Elizabeth Cosgriff-Hernandez, to co-develop an innovative strategy that addresses the pathophysiology of re-entrant arrhythmia.
Ventricular arrhythmia, which occurs in the lower chambers of the heart or ventricles, is the leading cause of sudden cardiac death in the United States.
When heart rhythm abnormality occurs in a self-sustained manner, it is called re-entrant arrhythmia, which is usually fatal.
“Re-entry occurs mainly from delayed conduction in scarred heart tissues, usually after coronary artery occlusion during a heart attack, which can be corrected by enabling pacing in these regions,” said Dr. Razavi, a practicing cardiologist and cardiac electrophysiologist.
“These hydrogels then can access the scarred tissue, thereby enabling direct pacing of the otherwise inaccessible regions of the heart.”
Given hydrogels’ biostability, biocompatibility, tunable properties, and the ease of incorporating electrical conductivity, the scientists are exploring them as potential electrodes that can be easily delivered inside coronary veins.
A clinical advantage of the unique system is that ischemia can be avoided by delivering the hydrogel using the veins.
The researchers successfully deployed the innovative hydrogel technology through minimally invasive catheter delivery in a pig model.
“The hydrogels have significant conductive properties that enable simultaneous pacing from multiple sites along the length of the hydrogel and create a conduction highway similar to those in Purkinje fibers,” according to Dr. Cosgriff-Hernandez.
Today, arrhythmia is treatable with medicines and procedures that control the irregular rhythms.
The current anti-arrhythmic drugs on the market are not always effective; although the drugs slow the conduction velocity, they facilitate re-entry arrhythmia.
Moreover, these drugs can be toxic and can lead to the destruction of tissues near the diseased regions of the heart.
Even with the widely used interventional ablation therapies, arrhythmia recurs in a significant proportion of patients. None of these procedures address the mechanism of re-entry.
Cardiac defibrillators implanted to compensate for the shortfalls in the current therapy options are painful when delivering electric shocks to restore heart rhythm and can severely deteriorate the patient’s quality of life.
If left untreated, arrhythmia can damage the heart, brain, or other organs, leading to stroke or cardiac arrest, during which the heart suddenly and unexpectedly stops beating.
“When injected into target vessels, the conductive hydrogel conforms to the patient’s vessel morphology. Adding a traditional pacemaker to this gel allows for pacing that resembles the native conduction in the heart — effectively mimicking the native electrical rhythm of the heart — and extinguishes the cause for arrhythmia, providing painless defibrillation,” added Dr. Cosgriff-Hernandez.
The work demonstrates for the first time the ability to confer direct electrical stimulation of the native and scarred mid-myocardium through injectable hydrogel electrodes as a pacing modality.
With minimally invasive catheter delivery and standard pacemaker technologies, this study indicates the feasibility of a novel pacing modality that resembles native conduction, potentially eliminating lethal re-entrant arrhythmia and providing painless defibrillation, which can be successfully adopted in a clinical workflow.
The scientific advance is significant considering pain management is highly relevant to overall wellness for patients with heart, lung, and blood diseases.
Such innovation in painless defibrillation and preventing arrhythmia could revolutionize cardiac rhythm management.
Researchers at the Chinese Academy of Sciences have developed an innovative scaffold that regulates the immune microenvironment following a spinal cord injury, thereby reduces secondary injury effects. Their work is reported in Biomaterials.
By modifying a hydrogel with a cationic polymer, polyamidoamine, and interleukin-10 (IL-10; an anti-inflammatory cytokine), the scaffold could enhance tissue remodelling and promote axonal regeneration.
Spinal cord injuries cause axon damage and neural cell death, leading to dysfunction. A secondary stage of injury follows the primary stage and lasts for several weeks. Infiltration and activation of immune cells triggered by a spinal cord injury creates an inflammatory microenvironment characterised with damage-associated molecular patterns (DAMPs) that exacerbates secondary damage and impairs neurological functional recovery.
With the capabilities of effective scavenging of DAMPs and sustained release of IL-10, such a dual-functional immunoregulatory hydrogel not only reduced pro-inflammatory responses of macrophages and microglia, but also enhanced neurogenic differentiation of neural stem cells.
In a mouse model of spinal cord injury, the scaffold suppressed cytokine production, counteracting the inflammatory microenvironment and regulating immune cell activation, resulting in neural regeneration and axon growth without scar formation.
The dual-functional immunoregulatory scaffold with neuroprotection and neural regeneration effects significantly promoted electrophysiological enhancement and motor function recovery after spinal cord injury.
This study suggests that functional scaffold reconstruction of the immune microenvironment is a promising and effective method for treating severe spinal cord injury.
A quarter of people with diabetes develop foot ulcers, which are slow to heal due to hypoxic conditions in the wound from impaired blood vessels and increased inflammation. These wounds can become chronic, leading to poor quality of life and possibly amputation.
Jianjun Guan, professor of mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has developed a hydrogel that delivers oxygen to a wound and decreases inflammation, helps to remodel tissue and speeds up healing. The results are published in Science Advances.
Prof Guan’s new hydrogel uses microspheres to gradually release oxygen to interact with the cells by means of an enzyme coating that converts the microsphere’s contents into oxygen. In this way, the hydrogel delivers oxygen over two weeks, reducing inflammation and promoting healing. “The oxygen has two roles: one, to improve skin cell survival under the low-oxygen condition of the diabetic wound; and two, oxygen can stimulate the skin cells to produce growth factors necessary for wound repair,” Prof Guan said.
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.
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.
Scientists have developed an injectable gel that serves as a biodegradable adhesive for various kinds of soft tissue injury.
Soft tissue tears are a common injury, and it is difficult for surgeons to secure the tissue back together, since stitches often do more harm than good. According to Dominique Pioletti, the head of the Laboratory of Biomechanical Orthopedics at EPFL’s School of Engineering, such surgeries often don’t produce the best results because the tissue doesn’t properly heal.
Tears in tissue such as cartilage and the cornea, often fail to heal properly, and tissue repair strategies may be suboptimal. For example, loose pieces of cartilage are often excised for symptomatic relief, but the remaining cartilage in articulating joints is placed under greater burden and generates faster.
A long-standing goal for researchers around the world has been the development of an adhesive for soft tissue that can withstand the natural stresses and strains within the human body. Now, Pioletti’s group has come up with a novel family of injectable biomaterials that can adhere to various forms of soft tissue. Their gel-based bioadhesives, can be used in a variety of injury-treatment applications. Like other hydrogels, this one has a high water content, 85%, and also has two key advantages: It is injectable anywhere in the human body, and it has high intrinsic adhesion without additional surface treatment. “What makes our hydrogel different is that it changes consistency while providing high adhesion to soft tissues,” said Peyman Karami, a postdoc at Pioletti’s lab who has developed the gel during his PhD. “It’s injected in a liquid form, but then sets when a light source is applied, enabling it to adhere to surrounding tissue.”
The hydrogel has an innovative design that allows its mechanical and adhesive properties to be tailored, making it an extremely versatile soft tissue glue that can be used throughout the human body.
To obtain these versatile properties in their hydrogel, the scientists took the base polymer and modified it with the compounds that play an important role in tissue adhesion. The first is known as Dopa and is derived from mussels. “Dopa is what lets mussels attach firmly to any kind of surface—organic or otherwise,” said Pioletti. The second is an amino acid that our bodies make naturally.
“The advantage of our hydrogel compounds is that, unlike some medical adhesives, they don’t interfere with the body’s chemical reactions, meaning our hydrogel is fully biocompatible,” said Karami.
The new hydrogel also possesses unique energy-dissipation characteristics that improve its adhesive capability. Karami added: “We had to achieve an adhesion mechanism for injectable hydrogels, through the resulting synergy between interfacial chemistry and hydrogel mechanical properties. The hydrogel is capable of dissipating the mechanical energy produced when the hydrogel deforms, so that it protects the interactions at the interface between the hydrogel and surrounding tissue.”
A further advantage of this hydrogel is that it can release drugs or cells to encourage tissue repair, which is especially beneficial for cartilage and other tissues that don’t regenerate on their own.
“Our in vitro tests showed that the hydrogel binds to many different kinds of tissue, including cartilage, meniscus, heart, liver, lung, kidney and cornea,” said Pioletti. “We’ve made a sort of universal hydrogel.”
The scientists have received a grant to research possible orthopedic applications of the gel, and hope to be able to release their innovation onto the market within the next five years.
Journal information: An intrinsically‐adhesive family of injectable and photo‐curable hydrogels with functional physicochemical performance for regenerative medicine, Macromolecular Rapid Communications, DOI :10.100 2/marc.202000660
