Synthesis of a mechano-responsive molecular brush with tuned biomimetic architectures

People involved: Simone Vesentini, Alfonso Gautieri, Marco Rasponi, Francesco Piraino

Funding source: Fondazione Cariplo

Funding period: 2012 - 2015

Partners: Department of Biochemistry, University of Pavia; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Department of Human Morphology, University of Insubria; Experimental Medicine Department of the Genova University.

The aim of the proposal is to synthesize a mechano responsive molecular brush with tuned biomimetic architectures using the natural aggrecan as blueprint . The envisioned aggrecan substituent, the COLLAGGRECAN, will be a macromolecule that not only mimics the relevant characteristics of the natural ECM aggrecan but it will also be characterized by an optimized arrangement of its molecular building blocks, with regards to the mechanical response. The lack of efficient treatment strategies for cartilage defects has motivated attempts to engineer cartilage constructs in vitro. However, none of the current strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The result is typically a suboptimal repair: the biochemical and mechanical properties of the regenerated cartilage do not match those of the native cartilage. The reason is that the astonishing behavior of this tissue resides in the molecular features of the cartilage ECM. A possible solution to increase both the biochemical and the mechanical properties of new generation constructs would be the use of aggrecan itself or, and this is our strategy, the synthesis of new biomimetic substituents of the aggrecan with simplified but effective and optimized molecular features. Since the unique properties of aggrecan arise from its molecular structure and composition, the most promising strategy to build an aggrecan substituent with analogue properties is:
1. to investigate the effect of particular nano-features on the behavior of the whole molecule;
2. to extract and analyze the molecular building blocks;
3. to synthesize the new molecules with the molecules previously extracted and with the optimization design criteria previously outlined;
4. to verify the morphology of the new molecules;
5. to analyze their biological behavior.