How to grow a new bone
Researchers at the Massachusetts Institute of Technology, working under the guidance of Professor Paula Hammond, have developed a new biodegradable framework for the restoration of large bone defects. When implanted into the damaged area, the skeleton slowly releases growth factors applied to its surface for several weeks, stimulating the rapid formation of new bone tissue, which practically does not differ from normal.
The two most important bone growth factors are platelet growth factor (PDGF, platelet-derived growth factor) and bone morphogenetic protein-2 (BMP-2, bone morphogenetic protein). The synthesis and release of PDGF is one of the first stages of the recovery cascade triggered by the body in case of bone injuries. After that, in order to create the microenvironment necessary for the attraction and differentiation of stem cells, as well as the formation of auxiliary structures, such as blood vessels, the synthesis of other factors, including BMP-2, is started.
Attempts to treat bone defects with the help of growth factors did not lead to the desired results due to the inability to accurately control the rate of administration and the administered dosages. When large doses are administered at a high rate, growth factors are rapidly removed from the damage zone, which reduces their contribution to tissue repair and can lead to undesirable side effects.
The recovery process is rather slow, so growth factors should enter the damage area gradually over several days or weeks. To ensure such a regime, the authors have developed a very thin porous material covered with layers of PDGF and BMP, from which a fragment in the form of a bone defect can be cut.
The frame, which is approximately 0.1 millimeters thick, is a membrane made of a biodegradable polymer polylactide-co-glycolide [poly(lactic-co-glycolic acid), PLGA], on which approximately 40 layers of BMP-2 are first applied by layer-by-layer assembly, which are covered with about 40 more layers of PDGF. This provides rapid release of PDGF and delayed slower release of BMP-2.
The authors tested their development on rats with skull defects that could not be independently repaired, the size of which reached 8 mm in diameter. PDGF, released during the first days after implantation, contributed to the launch of the recovery cascade and the mobilization of various progenitor cells in the area of damage. These cells, in turn, provided the formation of new tissues, including blood vessels and other auxiliary structures.
After that, the more slowly released BMP-2 induced the transformation of part of the immature progenitor cells into osteoblasts forming bone tissue.
As a result, within two weeks after implantation, a layer of bone was formed in the area of damage, indistinguishable in appearance and mechanical properties from natural bone tissue.
The developers have already launched the process of patenting the new frame and plan to test it on larger animal models in the near future.
Article by Nisarg J. Shah et al. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from MIT: Engineering new bone growth.
20.08.2014