Innovative researchers have investigated the possibility of functionally integrating methacryloyl gelatin hydrogel with nanosynthetic labonite to improve the conduction of osteoblast-derived extracellular vesicles to increase bone repair. This research was published in International Journal of Molecular Sciences As a bone repair strategy that may help reduce the burden of bone damage.
Study: Controlled release of genetically enhanced extracellular vesicles from a GelMA/Nanoclay composite hydrogel to promote bone repair. Image Credit: eranicle / Shutterstock.com
As bone fracture treatment represents a global social and economic burden, research has been carried out into new therapies such as the use of extracellular vesicles.
Why are new bone fracture treatments necessary?
There are approximately 10 million people within the UK who have developed musculoskeletal disorders, in addition to 1.71 billion people diagnosed worldwide, according to the World Health Organization (WHO). Additionally, a report on osteoporosis states that the disorder is responsible for 8.9 million fractures annually worldwide.
With an aging population, bone health has become a global concern and thus the demand for orthopedic-related treatments is only increasing, illustrating the necessity of research in this field to maintain the exponential growth as well as maintain 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 treatment route may not be the most effective for bone repair.
In addition, other treatment options have shown positive clinical outcomes, such as the combination of bone graft substitutes and bone-inducing growth factors including osteoblastic protein-2. This pathway can also cause complications with negative effects such as hematomas and myelopathy.
The limitations of these current bone repair strategies have led to the need for more innovative approaches to regenerate damaged bone.
This field of cell-based tissue engineering has been found to be promising with the incorporation of bone biomaterials with mesenchymal stromal cells (MSCs) for bone augmentation, however, direct implantation of MSC-based therapies has been shown to have induced adverse effects including immune rejection and impaired differentiation. Controlled and even neoplastic formation.
Other limitations of cell-based therapies for clinical translation include cost, lack of manufacturing scalability, and government regulations as well as potential ethical issues.
This realization led researchers to investigate cell-free strategies as a way to promote bone regeneration and repair disease and disorders.
An innovative approach to orthopedic repair
The potential key to bone regeneration could be extracellular vesicles (EV) as these acellular tools are lipid nanoparticles that can carry a variety of biological charges, such as nucleic acids and proteins.
These naturally-derived nanoparticles play an important function in bone growth with roles in mediating intercellular communication between osteoblasts and osteoblasts, the osteoblasts that make and break down bone tissue, respectively.
In addition, the inclusion of epigenetics to modulate the differentiating ability of cells to augment bone holds the potential to enhance EV mineralization.
Previous research has found that EVs isolated from osteoblasts and treated with the histone deacetylase inhibitor Trichostatin A (TSA) can lead to enhanced osteogenic potency, which may be due to enrichment in pro-osteoblast microRNAs and transcription-regulating proteins.
However, the problem with EV consists of a short half-life that limits its therapeutic benefit, with local administration into the defect area having transient results and requiring effective injections to be clinically successful.
This demonstrates the need for progress to facilitate efficient delivery of electric vehicles in order to improve their bioavailability On site.
New research has involved the use of methacryloyl (GelMA) gelatinous hydrogels employed with nano-synthetic labonite (LAP) to improve local retention and control of TSA- and osteoblast-derived EVs that are genetically optimized for bone repair.
This innovative combination was found to enhance the proliferation of human bone marrow stromal cells (hBMSCs) in addition to increasing migration, histone acetylation and mineralization compared to the control group of untreated EVs. In addition, GelMA-LAP hydrogel from TSA-EV was able to significantly enhance hBMSCs extracellular matrix collagen production as well as increase mineralization.
This demonstrates the importance of combining epigenetics through the histone deacetylase inhibitor Trichostatin A (TSA) with bone-derived electrophoresis as well as a nano-composite hydrogel that was able to enhance the delivery therapeutic efficacy for bone repair and regeneration.
The translation of this research consists of the development of the use of EVs as a pro-osteogenesis acellular tool; This has the benefit of not using cell-based therapy which can have complications such as high cost as well as immune rejection. In addition, this innovative approach also solves the half-life challenge originally attributed to electric vehicles.
This nanotechnology has the potential to be used clinically as a way to enhance bone regeneration, an area with limited therapies and thus innovative development could lead to high-quality care for the world’s aging population.
Continue reading: Analysis of novel orthodontic composite resins with nanoparticles for antibacterial properties.
Man, K., Barroso, I., Brunet, M., Peacock, B., Federici, A., Hoey, D. and Cox, S., (2022) Controlled release of genetically enhanced extracellular vesicles from GelMA/hydrogel Nanoclay complex to promote bone repair. International Journal of Molecular Sciences, 23 (2), p. 832. Available at: https://www.mdpi.com/1422-0067/23/2/832
Osteoporosis. (2022) Epidemiology of osteoporosis and fragility fractures | International Osteoporosis Foundation. [online] Available at: https://www.osteoporosis.foundation/facts-statistics/epidemiology-of-osteoporosis-and-fragility-fractures
Who.int. (2022) Diseases of the musculoskeletal system. [online] Available at: https://www.who.int/news-room/fact-sheets/detail/musculoskeletal-conditions#:~:text=Approxually%201.71%20billion%20people%20have%20musculoskeletal%20conditions%20worldwide., burden %20 with %20a%20 prevalence%20of%20568%20million%20 people.