Scientists from the Biotechnology Center (BIOTEC) and the Medical Faculty of TU Dresden have teamed up with researchers from Max Bergmann Center of Biomaterials (MBC) to develop innovative bio-inspired molecules that can improve bone regeneration in mice. The study’s findings were published in the Biomaterials journal.
With age, bone regeneration capability declines, making fractures and diseases like osteoporosis more challenging to treat. This poses a significant health issue for the aging population and an increasing economic burden on society. Therefore, researchers are exploring new therapeutic methods to improve bone regeneration.
Using computer modeling and simulations, the team created new bio-inspired molecules that can enhance bone regeneration in mice. These molecules can be incorporated into biomaterials and applied locally to treat bone defects. They are based on glycosaminoglycans, which are long-chain sugars, including hyaluronic acid and heparin.
A sweet solution for an old bone
Professor Lorenz Hofbauer explains that through their research and that of other scientists, they have identified a distinct molecular pathway that regulates bone repair and formation. Specifically, they have identified two proteins, sclerostin and dickkopf-1, which work together to inhibit bone regeneration. The challenge now is to develop drugs that can effectively block both of these proteins, which act as signals to slow down bone healing.
To tackle this challenge, an interdisciplinary approach was crucial. The Biotechnology Center’s Structural Bioinformatics group, led by Professor Maria Teresa Pisabarro, and the Max Bergmann Center’s Functional Biomaterials group, led by PD Dr. Vera Hintze, combined their expertise with bone specialist Professor Lorenz Hofbauer at the TU Dresden Medical Faculty.
Professor Pisabarro explains that her team used computer simulations to study how proteins that regulate bone formation interact with their receptors. By designing new molecules and testing them, they were able to gain insights into the molecular properties required to achieve their goal.
Finally, the team at Lorenz Hofbauer’s Bone Lab tested the effectiveness of a biomaterial loaded with the new molecules on bone defects in mice. They found that materials containing the novel molecules performed better than the standard biomaterial, enhancing bone healing by up to 50%. This promising result indicates the potential of the new molecules in improving bone regeneration.
Value-added chain: From computer to the lab bench and back
The team of researchers utilized rational drug design to develop novel molecules that can effectively turn off the proteins responsible for blocking bone regeneration. By employing computational methods, they were able to predict and optimize the properties of the designed molecules, ensuring that they have minimal side effects and tailored properties for their intended purpose.
The Pisabarro group’s expertise in analyzing the 3D structures of the proteins that hinder bone regeneration was essential in modeling their interactions with their receptors. By identifying the “hot spots,” which are the specific properties necessary for biological interactions to occur, they were able to design novel molecules that could effectively hijack and turn off these proteins.
After synthesizing the molecules designed by the Pisabarro group, the Free University of Berlin colleagues analyzed their protein binding properties through biophysical interaction analysis. This allowed them to measure the strength of the molecules’ binding with the proteins and their interference with natural receptor binding. The results showed how effective each of the molecules could be at turning off the inhibitory proteins. The Hofbauer group then tested the biological relevance of these interaction studies using cell culture models and later in mice.
The team’s iterative testing methodology allowed for the refinement and improvement of their molecular models, which could guide the development of more effective molecules in the future. This approach also minimized the need for animal research, which was only used in the final phase of the project.
The team’s findings have significant implications for preclinical development, as the new molecules they designed have the potential to turn off the proteins that inhibit bone regeneration. This could lead to the development of better treatments for bone fractures and other bone-related conditions. Overall, the team’s interdisciplinary approach has yielded promising results for improving bone regeneration and addressing the challenges associated with an aging population.