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This cartilage template will heal your broken bones

See it in your way but a bone injury, especially a fracture or broken bones is one of the most regular incidents among orthopedic issues. As per Schwebel, Goetz & Sieben, a Minnesota based law firm, 6.8 million cases (fractures) come under the radar in the United States. Though significantly based upon a plethora of other statistical parameters such as age, sex, and geographical location, having a fracture is as common as taking medicines for other health issues. Equally, the process of getting back to a normal life is painful, costly and time taking. Therefore a group of scientists from the University of Connecticut( Uconn Health Team )has come up with a novel approach to heal bones via a hybrid hydrogel system.

A view of cartilage template formation

Under the guidance of Associate professor of orthopedic surgery, Syam Nukavarap, the team maneuvered a sophisticated system that uses the regenerative phenomenon of bones as an aid for creating a healing catalyst. An adult skeleton contains 200 bones of different shapes and sizes. Interestingly, the story behind the formation of bones and its healing affinity when injured has considerably provoked the scientific community, working in regenerative medicine. As far as the bones are considered, it has been discovered that they follow an intramembranous and an endochondral ossification, IO and EO method respectively. Although both the methods are immensely complex IO is held responsible for the formation of flat bones, and EO, on the other hand, forms long bones like femurs and humeri.

These two processes use generic mesenchymal stem cells (MSCs) that activates the growth of new bones. Although similar, IO is significantly easier to perform in a lab set up since MSCs can directly differentiate into bone-forming cells, escaping any additional steps. However, the process comes with constraints. To bypass these limitations related to IO method, the group has designed an extracellular matrix that uses hydrogels to guide and support the bone formation via EO. According to Nukavarapu, who has joint positions in the departments of biomedical engineering and materials science and engineering, studies based on matrix designs for endochondral ossification to regenerate and repair long bone was neglected for a long time. With the help of hybrid hydrogel method, an extracellular matrix was engineered by the team, that could support cartilage-template formation.

Nukavarapu further mentioned that vascularization is the primary reason for segmental bone defect repair and regeneration. The issue with bones that have followed IO method is caused by an absence of blood vessels, named as vascularization. Somehow IO does not of regenerate enough bone tissues that can be applied to large bone defects resulting from trauma or degenerative diseases such as osteoporosis. Even though a lot of experimentation has been performed, vascularizing bone regenerated with IO with accuracy is still difficult to achieve. On the flip side, vascularization is a natural outcome of EO that comes into play owing to the development of a cartilage template, chondrocyte hypertrophy, and eventual bone tissue formation.

The EO method demands accurate spatial and temporal balance among different elements, for example, cells, growth factors, and an extracellular matrix, or scaffold, placed on which the MSCs play their part i.e. attach, proliferate, and differentiate.

The team has uniquely combined two tissue regeneration supportive compounds such as fibrin and hyaluronan that give birth to the desired extracellular matrix. The work method is a is as follows: the Fibrin gel copies human bone mesenchymal stem cells and further progresses their condensation, a necessity for MSC differentiation into chondrogenic cells. On the other side, Hyaluronan - a biopolymer imitates further steps of the process owing to which already differentiated chondrogenic cells proliferate. This phenomenon is known as hypertrophic chondrogenic differentiation.

The research team hopes that the engineered cartilage templates with hypertrophic chondrocytes will stimulate bone and vessel forming factors plus will start the vascularized bone formation. Though the research is in its nascent stage, its promising applications can harbor a great future in the healthcare sector. The research has been published in the Journal of Biomedical Materials Research-Part B.

Source: UConn

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