Study

Bone tissue engineering with autologous or allogenic mesenchymal stem cells (MSCs) has been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre-clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial. Recently it was shown that that encapsulated hMSCs can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups.

Based upon the observation that HUVEC vascualarisation was modified by polymer length, we initiated an investigation using our GRGDS PIC cell culture biomimetic hydrogels, to see if strain stiffening could dictate stem cell fate. This 3D system is based on physiologically soft (~0.2–0.4 kPa) polyisocyano-peptide (PIC) gel, which was thought to be a close approximation of the adult stem cell niches present in the human body. Importantly this soft material shows biopolymer-like stress stiffening which can be altered without modifying the gel stiffness and porosity. Intriguingly we observed that osteogenic commitment and differentiation of mesenchymal stem cell, is modified by changing only the polymer length, not the matrix stiffness.

 

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