Rabbit cried: protein from tears will help restore cartilage tissue
Russian scientists have tested preparations of lactoferrin, a natural protein found in milk and tear fluid, on rabbits for the ability to stimulate tissue regeneration without scarring. It turned out that it can be used to "reconfigure" the healing process from scarring to regeneration. Specialists have managed to cure ear cartilage in experimental animals, but in the future the technology will be suitable for repairing other tissues. For more information about advanced research, see the Izvestia article.
Is it possible to control the regeneration of cartilage tissue
Researchers at the Institute of Regenerative Medicine at Sechenov University have found that lactoferrin, a natural protein found in milk and lacrimal fluid, is able to accelerate organotypic regeneration, that is, high—quality, scar—free tissue repair, as close as possible to its original structure. So far, we are talking about ear cartilage, but potentially with the help of lactoferrin it is possible to achieve the restoration of other types of tissues, scientists told Izvestia.
The restoration of complex tissues such as cartilage, bone or nerve remains one of the main tasks of modern medicine. These tissues are characterized by a low rate of renewal, a small number of dividing cells and a weak ability to self-repair. Often, after damage, not a full-fledged tissue is formed, but a scar that does not perform its original functions. Scientists have long been looking for ways to direct the healing process not just to fill in the defect, but to truly regenerate — like a lizard growing a tail.
In search of a solution, the researchers used the elastic cartilage of a rabbit's auricle as a model. This type of tissue is a rare example in mammals where, under certain conditions, complete, high—quality scar-free recovery is possible. The team continued previous work to establish the necessary conditions for regeneration by conducting exploratory research with a range of drugs and factors with known effects on tissue healing.
Experiments on cells have shown that lactoferrin increases cell survival and stimulates the synthesis of key components of healthy cartilage. However, the main discovery was made in an animal study. When locally injected into the area of damage to the cartilage of the auricle, lactoferrin not only accelerated healing, but directed the process towards organotypic regeneration. By day 60, areas with a high density of elastic fibers were already forming in the experimental group. By day 90, the defect was replaced by full-fledged cartilage tissue, structurally indistinguishable from healthy tissue.
—The ear cartilage is one of the few mammalian models where high—quality regeneration can be observed," explained Alexey Fayzullin, head of the Laboratory of Digital Microscopic Analysis. — We tested several biologically active substances and drugs and drew attention to lactoferrin, which accelerated organotypic recovery — when the tissue does not scar, but its original architecture is recreated. This is an important step: we have found out that it is possible to "reconfigure" the healing process from scarring to regeneration.
How can lactoferrin be used?
Lactoferrin's ability to stimulate not just cell growth, but qualitative recovery opens the way to the creation of fundamentally new methods of treating damage to complex structures, from cartilage and bone to, possibly, nervous tissue.
"The use of lactoferrin in bioprinting tissue—engineered structures can significantly accelerate the formation and maturation of cartilage structures, as well as improve their quality," said Artem Antoshin, head of the Center for Innovative Collagen Research at Sechenov University, Candidate of Medical Sciences. — Due to these properties, it can become an extremely useful additive to nutrient media during cell cultivation.
The research opens up new horizons in regenerative medicine. It is known that this natural protein, contained in milk and tears, can trigger the process of full-fledged tissue repair with its complex structure, Yulia Samoilova, a market expert at NTI Helsnet, director of the Institute of Medicine and Medical Technologies at NSU, told Izvestia.
According to her, its ability to stimulate the growth of elastic cartilage is particularly impressive, which has been demonstrated on models of the auricle. This area is particularly promising for patients with birth defects or the effects of injury, where modern methods require complex operations involving the patient's own tissue transplantation.
"In the future, lactoferrin may complement cellular technologies and be used in combination with other regenerative agents, such as platelet plasma or exosomes. The development brings closer the era of more gentle and effective methods of reconstructive surgery that can improve the quality of life of patients," the expert said.
The study fits perfectly into current trends in bioengineering, where the focus is shifting to the intelligent regulation of regeneration processes, said Stanislav Stragnov, head of the Laboratory for the Analysis of Public Health indicators and Digitalization of Healthcare at MIPT.
— I would like to believe that lactoferrin will become an important component of "smart" bio-ink for 3D printing of tissues, personalized implants and combination therapies, allowing not only prosthetics, but also launching self-healing programs. But for now we are talking about models and model animals," the scientist said.
The work concerns one of the most commercially promising segments of biomedicine. The problem of restoring cartilage tissue is extremely important for orthopedics and traumatology, and high-quality regeneration technology could significantly reduce the need for endoprosthetics, said Maxim Kolyasnikov, Associate Professor at the UrFU Institute of Economics and Management and the Department of Future Technologies at MIPT.
— The key economic advantage of the development is the use of lactoferrin, a natural protein that is already produced industrially and is relatively inexpensive. However, competition in the segment is intense: Chinese researchers recently introduced a bioadhesive gel for bone repair based on nanoparticles, which also showed the ability to stimulate regeneration without scarring, receiving substantial government funding and an accelerated path to clinical trials, the expert noted.
According to him, the study was conducted on a specific model of rabbit ear cartilage, which has a unique regenerative ability that is atypical for human articular cartilage. The path from proof of concept to clinical application takes 7-10 years and will require investments of hundreds of millions of rubles.
The progress of the development will depend on success in solving fundamental tasks: achieving specificity of exposure in a complex biological network of the body and creating delivery systems that ensure the transition from laboratory conditions to clinical practice, concluded the expert of NTI "Helsnet", head of the laboratory of pharmacological active compounds, Research Institute of Clinical and Experimental Lymphology, a branch of the Institute of Cytology and Genetics SB RAS. Anastasia Solovyova.
The work, supported by a grant from the Russian Science Foundation, has been published in the International Journal of Molecular Sciences.
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