Innovative researchers have investigated the potential of incorporating a gelatin methacryloyl hydrogel functionalized with synthetic nanoclay laponite to improve the delivery of osteoblast derived extracellular vesicles for increased bone repair. This research has been published in the International Journal of Molecular Sciences as a bone repair strategy that may aid in alleviating the burden of bone damage.
With bone fracture treatment being a global socioeconomic burden, research into novel treatments has been undertaken such as the use of extracellular vesicles.
Why Are Novel Bone Fracture Treatments Necessary?
There are approximately 10 million people within the UK who have been affected by musculoskeletal disorders, as well as 1.71 billion diagnosed worldwide, as reported by the World Health Organization (WHO). Additionally, a report on osteoporosis has stated this disorder is responsible for 8.9 million fractures annually, worldwide.
With an ageing population, bone health has become a concern globally and so the demand for bone-related treatments is only increasing, illustrating the necessity of research for this field to sustain the exponential growth as well as retain the quality of life for patients.
Autologous bone grafts are currently the gold standard for treating diseased or damaged bones; however, with limitations such as lack of availability, accessibility and donor site morbidity, this route of treatment may not be the most efficient for bone repair.
Additionally, other treatment options have shown positive clinical results, such as combining bone graft substitutes with osteoinductive growth factors including bone morphogenic protein 2. This route can also cause complications with adverse effects such as hematomas and myelopathy.
This field of cell-based tissue engineering has been found to show promise with osteoinductive biomaterials being combined with mesenchymal stromal cells (MSCs) for bone augmentation, however, direct transplant of MSC-based therapies has been shown to have produced adverse effects including immunological rejection, uncontrolled differentiation and even the formation of neoplasms.
Other limitations for cell-based therapies for clinical translation also include cost, lack of scalability within manufacturing, governmental regulations as well as potential ethical issues.
This realization has led researchers to investigate cell-free strategies as a method to promote bone regeneration and repair for diseases and disorders.
Innovative Bone Repair Approach
Extracellular vesicles (EV) could be the potential key to bone regeneration, with these acellular tools being lipid nanoparticles that can carry a diverse range of biological cargo, such as nucleic acids and proteins.
These naturally derived nanoparticles hold a significant function in bone development with roles in mediating intercellular communication between osteoblasts and osteoclasts, bone cells that synthesize and break down bone tissue, respectively.
Additionally, the inclusion of epigenetics to modify the differentiation capacity of cells for bone augmentation holds the potential to enhance EV mineralization.
Previous research has found EVs that are isolated from osteoblasts and treated with the histone deacetylase inhibitor Trichostatin A (TSA), can lead to enhanced osteoinductive potency, which may be due to enrichment in pro-osteogenic microRNAs and transcriptional regulating proteins.
However, the issue with EV consists of the short half-life which limits their therapeutic utility, with local administration into the defect area having transient results and requiring effective injections to be clinically successful.
This illustrates the necessity for advancements to effectively facilitate the delivery of EVs in order to improve their bioavailability in situ.
Innovative Research
Novel research has included the utilization of gelatin methacryloyl (GelMA) hydrogels which were functionalized with synthetic nanoclay laponite (LAP) with the aim of improving local retention and control delivery of osteoblast-derived and TSA treated EVs that have been epigenetically enhanced for bone repair.
This innovative combination has been found to enhance the proliferation of human bone marrow stromal cells (hBMSCs) as well as increasing migration, histone acetylation and mineralization compared to the control group of untreated EVs. Additionally, the TSA-EV functionalized GelMA-LAP hydrogel was able to significantly promote encapsulated hBMSCs extracellular matrix collagen production as well as increase mineralization.
This illustrates the significance of combining epigenetics through the histone deacetylase inhibitor Trichostatin A (TSA) with osteoblast-derived EVs as well as a nanocomposite hydrogel which was able to enhance the therapeutic efficacy of delivery for bone repair and regeneration.
Future Translation
The translation for this research consists of the development of using EVs as a pro-osteogenic acellular tool; this has the benefit of not using a cell-based therapy which can have complications such as high expense as well as immune rejection. Additionally, this innovative approach also solves the challenge of the half-life originally attributed to EVs.
This nanotechnology has the potential to be used clinically as a method to promote bone regeneration, a field that has limited treatments and so an innovative development can lead to quality care of a global aging population.
News
Johns Hopkins Researchers Uncover a New Way To Kill Cancer Cells
A new study reveals that blocking ribosomal RNA production rewires cancer cell behavior and could help treat genetically unstable tumors. Researchers at the Johns Hopkins Kimmel Cancer Center and the Department of Radiation Oncology and Molecular [...]
AI matches doctors in mapping lung tumors for radiation therapy
In radiation therapy, precision can save lives. Oncologists must carefully map the size and location of a tumor before delivering high-dose radiation to destroy cancer cells while sparing healthy tissue. But this process, called [...]
Scientists Finally “See” Key Protein That Controls Inflammation
Researchers used advanced microscopy to uncover important protein structures. For the first time, two important protein structures in the human body are being visualized, thanks in part to cutting-edge technology at the University of [...]
AI tool detects 9 types of dementia from a single brain scan
Mayo Clinic researchers have developed a new artificial intelligence (AI) tool that helps clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using a single, widely available scan—a transformative [...]
Is plastic packaging putting more than just food on your plate?
New research reveals that common food packaging and utensils can shed microscopic plastics into our food, prompting urgent calls for stricter testing and updated regulations to protect public health. Beyond microplastics: The analysis intentionally [...]
Aging Spreads Through the Bloodstream
Summary: New research reveals that aging isn’t just a local cellular process—it can spread throughout the body via the bloodstream. A redox-sensitive protein called ReHMGB1, secreted by senescent cells, was found to trigger aging features [...]
AI and nanomedicine find rare biomarkers for prostrate cancer and atherosclerosis
Imagine a stadium packed with 75,000 fans, all wearing green and white jerseys—except one person in a solid green shirt. Finding that person would be tough. That's how hard it is for scientists to [...]
Are Pesticides Breeding the Next Pandemic? Experts Warn of Fungal Superbugs
Fungicides used in agriculture have been linked to an increase in resistance to antifungal drugs in both humans and animals. Fungal infections are on the rise, and two UC Davis infectious disease experts, Dr. George Thompson [...]
Scientists Crack the 500-Million-Year-Old Code That Controls Your Immune System
A collaborative team from Penn Medicine and Penn Engineering has uncovered the mathematical principles behind a 500-million-year-old protein network that determines whether foreign materials are recognized as friend or foe. How does your body [...]
Team discovers how tiny parts of cells stay organized, new insights for blocking cancer growth
A team of international researchers led by scientists at City of Hope provides the most thorough account yet of an elusive target for cancer treatment. Published in Science Advances, the study suggests a complex signaling [...]
Nanomaterials in Ophthalmology: A Review
Eye diseases are becoming more common. In 2020, over 250 million people had mild vision problems, and 295 million experienced moderate to severe ocular conditions. In response, researchers are turning to nanotechnology and nanomaterials—tools that are transforming [...]
Natural Plant Extract Removes up to 90% of Microplastics From Water
Researchers found that natural polymers derived from okra and fenugreek are highly effective at removing microplastics from water. The same sticky substances that make okra slimy and give fenugreek its gel-like texture could help [...]
Instant coffee may damage your eyes, genetic study finds
A new genetic study shows that just one extra cup of instant coffee a day could significantly increase your risk of developing dry AMD, shedding fresh light on how our daily beverage choices may [...]
Nanoneedle patch offers painless alternative to traditional cancer biopsies
A patch containing tens of millions of microscopic nanoneedles could soon replace traditional biopsies, scientists have found. The patch offers a painless and less invasive alternative for millions of patients worldwide who undergo biopsies [...]
Small antibodies provide broad protection against SARS coronaviruses
Scientists have discovered a unique class of small antibodies that are strongly protective against a wide range of SARS coronaviruses, including SARS-CoV-1 and numerous early and recent SARS-CoV-2 variants. The unique antibodies target an [...]
Controlling This One Molecule Could Halt Alzheimer’s in Its Tracks
New research identifies the immune molecule STING as a driver of brain damage in Alzheimer’s. A new approach to Alzheimer’s disease has led to an exciting discovery that could help stop the devastating cognitive decline [...]
