Hydrogel scaffold raises hopes for tissue regeneration

Wyss Institute hydrogel therapy can repair nerves, muscles and blood vessels.

Naturally-occurring molecules VEGF and IGF-1 can enhance tissue regrowth and repair, but getting them to where they are needed has proved problematic. Enter an alginate hydrogel, a biocompatible scaffold that can ensure the release of the necessary molecules at the injury site.

Longevity.Technology: Hydrogels are proving to be a neat weapon in the tissue regrowth arsenal. As well as providing chemical and mechanical signals, they are an ideal environment for cells to adhere, proliferate, and differentiate, meaning drugs can be delivered and tissues engineered. Commercialisation was originally limited due to the high cost of hydrogel production, but as more labs push towards getting hydrogels out for mainstream therapy, the cost is coming down.

The components of the VEGF/IGF hydrogel can be easily manufactured as “kits” that can be purchased by users in the regenerative medicine field, hospitals, private practices, etc. Credit: Wyss Institute at Harvard University

Bodies are pretty impressive when it comes to healing themselves, but some consequences of injury, disease and degeneration – like the severing of a nerve, or sustained oxygen deprivation – can lead to permanent loss of movement or sensation in a limb and a huge impact on mobility and quality of life.

Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates the formation of blood vessels. When coupled with insulin-like growth factor-1 (IGF-1), which stimulates systemic body growth and repair and regulates cellular DNA synthesis, they make a powerful regenerative cocktail.

Credit: Wyss Institute at Harvard University

However, simply injecting them into a patient is unworkable as a therapy, because as well as a very short duration of action and low regeneration efficacy, they prove to be toxic when delivered in this way.

Researchers at the Wyss Institute overcame this problem by loading VEGF and IGF-1 into a biocompatible hydrogel scaffold; this is then injected under the skin directly at the injury site. The alginate scaffold provides a sustained, non-toxic local release of these growth and repair factors, which results in significant repair of injured tissues.

“…[This] could finally break the logjam and allow the creation of truly revolutionary regenerative medicines.”

When tested in multiple preclinical lagomorphine and murine models, the hydrogel-delivered therapy showed a prolonged ability to restore muscular function and reverse nerve damage. Blood perfusion recovered to 80-90% and in just a few weeks, muscle strength was restored to pre-injury levels [1].

Lead researcher, David Mooney, core faculty member at the Wyss Institute said: “The promise of growth factors like VEGF and IGF-1 has been largely unrealized due to their systemic toxicity and poor duration of action with bolus injection. The fact that we can now deliver an effective, non-toxic dose of these molecules directly to target sites could finally break the logjam and allow the creation of truly revolutionary regenerative medicines [2].”

[1] https://www.sciencedirect.com/science/article/pii/S014296121930345X
[2] https://wyss.harvard.edu/technology/regenerating-tissues-with-sustained-growth-factor-delivery/

Media credits:  Wyss Institute for video and main image