The results, published in the journal Regenerative Medicine, showed that a single injection of leukocyte-rich/PRP in the knee joint significantly improved functional mobility, pain and quality of life after six weeks. The study supports using this combined approach to further evaluate this and other emerging biological therapies for musculoskeletal disorders in larger clinical trials.

“OA is a leading cause of disabilities, affecting nearly 52 million Americans,” said first and corresponding author Dr. Prathap Jayaram, director of regenerative sports medicine and assistant professor in the Department of Physical Medicine and Rehabilitation and Orthopedic Surgery at Baylor. “It has been estimated that more than 80% of individuals older than 55 years have some X-ray-based evidence of the disease.”

OA develops when the smooth cushion between bones, the cartilage, breaks down. Progressively, joints become painful, swollen and hard to move, Jayaram explained. Currently, there are no validated therapies that delay disease progression. The current standard of care is limited to the alleviation of symptoms with corticosteroids.

“However, although steroids seem to be helpful in the short term for pain, emerging evidence has associated steroid long-term use in OA with loss of cartilage,” Jayaram said. “As OA is a whole joint disease, there is a need for developing novel therapeutic strategies that ultimately prevent and/or delay disease progression while improving functional outcomes. PRP is emerging as one of the promising candidates to treat OA that are currently being used in clinical practice.”

Combining wearable technology and patient assessment to evaluate the treatment

One challenge of previous studies assessing PRP therapies in OA is that treatment evaluation is based on patient-reported outcomes that subjectively assess pain or aspects of joint function, such as the time up-and-go (TUG), how quick a person gets up from a chair.

In this study, Jayaram and colleagues incorporated wearable technology to objectively assess functional outcomes such as TUG, in addition to patient-reported outcomes to comprehensively evaluate the efficacy of PRP in knee OA (KOA).

The prospective pilot study included 12 patients diagnosed with KOA. Each patient received one ultrasound-guided injection of PRP and function and pain were evaluate six weeks later.

PRP is prepared from the patient’s own blood by removing the red blood cells and enriching the concentration of platelets. PRP also contains white blood cells, or leukocytes. PRPs are formulated either leucocyte-rich (LR) or leukocyte-poor. A preclinical study by Jayaram and his colleagues had previously shown that LR-PRP had potential disease-modifying effects that correlated with functional outcomes.

“In the current study, we found that a single injection of LR-PRP into the knee does significantly improve functional mobility, pain and quality of life at six weeks,” Jayaram said. “To our knowledge, our study is the first to report the efficacy of LR-PRP on objective functional outcomes using wearable sensor technology and validated patient-reported outcomes. Our findings provide the basis to conduct larger randomized clinical trials of PRP.”

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Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

These qualities allow hydrogels to simulate living tissue for tissue replacement or regeneration. One of the most useful of these applications is for healing wounds. Hydrogels are ideal for this purpose, with their ability to hydrate and form a moist and supportive environment. This facilitates processes beneficial for wound healing, such as blood vessel formation, the breakdown of dead tissue, activation of immune cells, the prevention of live cell and tissue death and even the alleviation of pain.

Natural hydrogels, particularly gelatin methacryloyl (GelMA) hydrogels, are favored for wound healing due to their biosafety and exceptional biocompatibility. But their usage is hampered by their inherently poor mechanical properties such as limited stretchiness, relative brittleness and inflexibility, and their inability to adhere to onto tissue surfaces. In order to improve upon these characteristics, variations on preparation methods and components have been attempted.

When a GelMA hydrogel is prepared, a solution of gelatin is made by mixing and dissolving gelatin in water. This results in a dispersion of gelatin polymer chains in the water. A chemical called a photo-initiator is then added to the solution, which makes the polymer chains sticky and allows them to stick to one another. Exposure to UV light activates the photo-initiators and the polymer chains cross-link to each other to form a network. Water molecules enter this network, stretching the chains and becoming locked within them; this illustrates the hydrogels’ absorptive powers and is the point where gelation, or solidification, occurs.

The properties of this gel can be modified by adding chemicals that bind to the polymer chains before UV exposure, or the UV parameters themselves can be varied to tune the gel’s properties. Some of these modifications have been experimented with in previous attempts to improve GelMA’s physical properties.

One approach was to introduce additional chemicals into the GelMA solution before crosslinking; the resultant chemically conjugated hydrogel showed a slight improvement in tissue adhesion. Other attempts have been made at strengthening GelMA by reinforcing flexible thin chemically conjugated GelMA films with additional chemicals. But challenges remain with improving the three mechanical properties of toughness, stretchiness, and adhesive strength simultaneously in GelMA hydrogels.

A collaborative team from the Terasaki Institute for Biomedical Innovation (TIBI) has developed methods for improving all three of these properties in GelMA hydrogels in a simple procedure with tunable fabrication parameters.

The researchers first turned to an example found in nature in their approach to improving adhesion in the hydrogels. Marine mussels secrete strong threads that are used as attachments and pulling ropes on rocks and other irregular surfaces. To form these threads, the mussels produce adhesion proteins in an acidic environment; upon exposure to the slightly alkaline ocean water, the proteins undergo a chemical change which spurs thread formation.

In a corresponding fashion, the TIBI team added large quantities of dopamine, a chemical analog to mussel adhesion protein, to GelMA to increase its strength, stretchiness, and adhesive properties. They also subjected the mixture to alkaline conditions to further increase the GelMA’s adhesive strength.

The results showed that the addition of large quantities of dopamine to the GelMA solution could increase the stretchiness of the resultant hydrogel by almost six-fold and its strength by more than three-fold. Other experiments showed that when the dopamine is subjected to alkaline conditions before the crosslinking step, the adhesive strength could be increased up to four times and its resistance to shear forces by almost seven-fold.

“The experiments we have conducted provide valuable insight into procedures for activating toughness and adhesion in GelMA-based hydrogels,” said Hossein Montazarian, Ph.D., first author of the project.

The researchers will continue to experiment with other chemicals to optimize their effects on GelMA’s mechanical properties. This can lead to improvements in additional applications such as skin-attachable wearable devices or healing and regenerative internal implants.

“The knowledge gained here on the fundamental mechanical properties of hydrogels can have far-reaching effects on biomedical applications,” said Ali Khademhosseini, Ph.D., TIBI’s Director and CEO. “It is one of many examples of impactful research from our biomaterials platform.”

This work was supported by funding from the National Institutes of Health (1R01EB023052-01A1, 1R01HL140618-01).

A hydrogen economy is one way in which a carbon neutral world can thrive. At present, the simplest way to produce hydrogen fuel is electrochemical water splitting: running electricity through water in the presence of catalysts (reaction-enhancing substances) to yield hydrogen and oxygen. This reaction, however, is very slow, requires specialized conditions and noble-metal catalysts, and is overall expensive. Thus, achieving a high hydrogen yield in an energy-efficient manner at low cost is challenging. To date, hydrogen production from water splitting has not been successfully commercialized.

Now, a team of researchers from Pusan National University, Korea, led by Professor Kandasamy Prabakar, have developed a method to design a novel electrocatalyst that can solve some of these problems. Their work was made available online on April 6, 2021, and will be published in print in the September 2021 issue of Volume 292 of Applied Catalysis B: Environmental.

Describing the study, Prof. Prabakar says, “Today, 90% of hydrogen is produced from steam reforming processes that emit greenhouse gases into the atmosphere. In our laboratory, we have developed a non-noble metal based stable electrocatalyst on a polymer support which can effectively produce hydrogen and oxygen from water at a low-cost from transition metal phosphates.”

Prof. Prabakar’s team fabricated this electrolyzer by depositing cobalt and manganese ions, in varying proportions, on a Polyaniline (PANI) nanowire array using a simple hydrothermal process. By tuning the Co/Mn ratio, they have achieved an overall high surface area for the reactions to occur, and combined with the high electron conducting capacity of the PANI nanowire, faster charge and mass transfer was facilitated on this catalyst surface. The bimetallic phosphate also confers bifunctional electrocatalytic activity for the simultaneous production of oxygen and hydrogen.

In experiments to test the performance of this catalyst, they found that its morphology substantially decreases the reaction overpotential, thereby improving the voltage efficiency of the system. As a testament to durability, even after 40 hours of continuous hydrogen production at 100 mA/cm², its performance remains consistent. And water splitting was possible at a low input voltage of merely 1.54V.

In addition to these advantages, is the low cost of transition metals. Indeed, the system can be scaled and adapted for application to a myriad of settings. Speaking of possible future applications, Prof. Prabakar explains, “Water-splitting devices that use this technology can be installed onsite where hydrogen fuel is required, and can function using a low energy input or a completely renewable source of energy. For instance, we can produce hydrogen at home for cooking and heating using a solar panel. This way, we can achieve carbon neutrality well before 2050.”

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Materials provided by Pusan National University. Original written by Na-hyun Lee. Note: Content may be edited for style and length.

The ENVISAGE-TAVI AF trial is the largest to investigate an edoxaban-based strategy in this patient population compared with warfarin, which is currently the standard of care. It demonstrates that edoxaban is non-inferior to warfarin. The results, which could lead to an alternative treatment strategy, were announced Saturday, August 28, as a late-breaking clinical trial at the ESC Congress 2021 from the European Society of Cardiology and simultaneously published in The New England Journal of Medicine.

“Atrial fibrillation after transcatheter aortic valve replacement is common, especially among older patients, but there has been little research on the optimal treatment strategies, and this has resulted in heterogeneous use of anticoagulants in clinical practice. TAVR patients are typically very elderly and possess numerous comorbidities; therefore they are at high risk for all sorts of adverse events, both ischemic and bleeding. It is important to further understand what treatment is most effective to prevent devastating complications,” says lead investigator George Dangas, MD, PhD, Professor of Medicine (Cardiology) and Director of Cardiovascular Innovation at the Zena and Michael A. Wiener Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai. “Based on these results, the trial met its primary endpoint of non-inferiority and edoxaban may be a plausible alternative to warfarin, albeit with attention to increased bleeding with this agent in this study population.”

Cardiologists prescribe antithrombotic agents — specifically warfarin, a vitamin K antagonist — to prevent thromboembolic complications in patients who have TAVR, a minimally invasive heart procedure to replace the aortic valve. Choosing the optimal antithrombotic regimen remains challenging, especially in patients with an underlying condition like AF — irregular rapid heartbeat that impacts blood flow — that requires the use of anticoagulants. Past studies have shown anywhere between 20-40 percent of TAVR patients have AF and a large proportion of them are frail, so a main challenge in managing their care involves balancing the risks of bleeding and stroke.

Until now, there has been minimal research into the optimal oral anticoagulation therapy in TAVR patients.

Mount Sinai researchers led an international trial across 173 centers in 14 countries to compare the safety and efficacy of edoxaban versus warfarin in AF patients who need oral anticoagulation. To determine efficacy, they looked at combined adverse clinical events including all-cause death, thromboembolic events, and major bleeding. For safety they looked at serious bleeding events. Investigators randomized 1,426 patients 5 to 12 days after TAVR to either warfarin (with or without antiplatelet therapy) or 60 mg daily oral edoxaban (with or without antiplatelet therapy). They followed up with patients for up to three years following TAVR (average of 18 months). The study findings showed that edoxaban was noninferior to warfarin for efficacy as assessed by a composite set of ischemic and bleeding adverse events. At the same time, edoxaban led to some higher bleeding complications (mainly gastrointestinal) when compared to warfarin (or its analogs as available in each country).

Interestingly, patients who received a lower dose of edoxaban (30 mg instead of 60 mg) due to poor kidney function or low body weight appeared to have similar rates of adverse thromboembolic and bleeding events to those on warfarin.

“The next step would be to establish in large randomized trials the optimal anticoagulant dose according to different bleeding-ischemic risk profiles,” adds Dr. Dangas. “It seems that lowering the edoxaban dosage when indicated and avoiding patients with mandatory antiplatelet therapy because of their elevated bleeding risk is reasonable safety advice from the clinical point of view. We will be conducting a detailed analysis on various types of bleeding in the near future. ENVISAGE-TAVI AF suggests that treatment with edoxaban can be valuable in the management of this high-risk population of AF patients after TAVI.”

ENVISAGE-TAVI AF was sponsored by Daiichi Sankyo Inc. with a scientific collaboration between scientists of Icahn Mount Sinai and Global Specialty Medical Affairs of Daiichi Sankyo.