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
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
Mystery Solved: Scientists Find Cause for Unexplained, Deadly Diseases
A study reveals that a protein called RPA is essential for maintaining chromosome stability by stimulating telomerase. New findings from the University of Wisconsin-Madison suggest that problems with a key protein that helps preserve chromosome stability [...]
Nanotech Blocks Infection and Speed Up Chronic Wound Recovery
A new nanotech-based formulation using quercetin and omega-3 fatty acids shows promise in halting bacterial biofilms and boosting skin cell repair. Scientists have developed a nanotechnology-based treatment to fight bacterial biofilms in wound infections. The [...]
Researchers propose five key questions for effective adoption of AI in clinical practice
While Artificial Intelligence (AI) can be a powerful tool that physicians can use to help diagnose their patients and has great potential to improve accuracy, efficiency and patient safety, it has its drawbacks. It [...]
Advancements and clinical translation of intelligent nanodrugs for breast cancer treatment
A comprehensive review in "Biofunct. Mater." meticulously details the most recent advancements and clinical translation of intelligent nanodrugs for breast cancer treatment. This paper presents an exhaustive overview of subtype-specific nanostrategies, the clinical benefits [...]
It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome
A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection. Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate [...]
How Far Can the Body Go? Scientists Find the Ultimate Limit of Human Endurance
Even the most elite endurance athletes can’t outrun biology. A new study finds that humans hit a metabolic ceiling at about 2.5 times their resting energy burn. When ultra-runners take on races that last [...]
World’s Rivers “Overdosing” on Human Antibiotics, Study Finds
Researchers estimate that approximately 8,500 tons of antibiotics enter river systems each year after passing through the human body and wastewater treatment processes. Rivers spanning millions of kilometers across the globe are contaminated with [...]
Yale Scientists Solve a Century-Old Brain Wave Mystery
Yale scientists traced gamma brain waves to thalamus-cortex interactions. The discovery could reveal how brain rhythms shape perception and disease. For more than a century, scientists have observed rhythmic waves of synchronized neuronal activity [...]
Can introducing peanuts early prevent allergies? Real-world data confirms it helps
New evidence from a large U.S. primary care network shows that early peanut introduction, endorsed in 2015 and 2017 guidelines, was followed by a marked decline in clinician-diagnosed peanut and overall food allergies among [...]
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
Self-Organizing Light Could Transform Computing and Communications
USC engineers have demonstrated a new kind of optical device that lets light organize its own route using the principles of thermodynamics. Instead of relying on switches or digital control, the light finds its own [...]
Groundbreaking New Way of Measuring Blood Pressure Could Save Thousands of Lives
A new method that improves the accuracy of interpreting blood pressure measurements taken at the ankle could be vital for individuals who are unable to have their blood pressure measured on the arm. A newly developed [...]
Scientist tackles key roadblock for AI in drug discovery
The drug development pipeline is a costly and lengthy process. Identifying high-quality "hit" compounds—those with high potency, selectivity, and favorable metabolic properties—at the earliest stages is important for reducing cost and accelerating the path [...]
Nanoplastics with environmental coatings can sneak past the skin’s defenses
Plastic is ubiquitous in the modern world, and it's notorious for taking a long time to completely break down in the environment - if it ever does. But even without breaking down completely, plastic [...]
