A shape-controlled tuneable microgel platform to modulate angiogenic paracrine responses in stem cells

作者：Thomas Dilip; Fontana Gianluca; Chen Xizhe; Sanz Nogues Clara; Zeugolis Dimitrios I; Dockery Peter; O'Brien Timothy; Pandit Abhay^*

来源：Biomaterials, 2014, 35(31): 8757-8766.

DOI：10.1016/j.biomaterials.2014.06.053

• Customised ECM matrices
• Microgels
• Mesenchymal stem cells
• Cell-factories
• Angiogenesis

Development of cell delivery platforms have been driven based on an empirical cytoprotective design. While cell-matrix and cell cell interactions that influence biochemical effects beyond survival has been limited and overshadowed in an effort to incrementally improve biomimicking properties of the tissue-engineered constructs. Here we demonstrate fabrication of a shape controlled 3D type-I collagen-based microgel platform that can be tuned to modulate angiogenic paracrine- 'angiocrine' responses of human mesenchymal stem cells (hMSCs). Furthermore, these microgels were characterized as a 3D cell culture tool to assess optimal biological response as a function of cell-matrix and cell-cell interactions. Finally, optimised hMSC embedded microgels were shown to induce vascular repair and functional improvement in vivo in a mouse model of hind-limb ischemia. The approach described here in designing a tuneable cell delivery platform using naturally occurring extracellular matrix molecules highlights the need for highly customised matrices with an array of self-assembling proteins that dictate specific cell function resembling the native tissue of interest for repair.

• 出版日期2014-10