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Engineering Cell Microenvironment Using Nanopattern-Derived Multicellular Spheroids and Photo-Crosslinked
Zhen Zhang1,2, Yi Liu3, Xuelian Tao1
1Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Polymers
|April 28, 2023
Summary
This study developed advanced multicellular spheroids using nanopatterns and hydrogels. The human bone mesenchymal stem cell/human umbilical vein endothelial cell co-spheroids demonstrated enhanced osteogenic differentiation and vascular network formation.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Cell Biology
Background:
- 3D cell cultures within hydrogels model cell-extracellular matrix (ECM) interactions.
- Coculturing cells in spheroids integrates cell-cell and cell-ECM interaction effects.
- Existing methods for spheroid formation, like low-adhesion surfaces, have limitations.
Purpose of the Study:
- To develop a novel method for creating human bone mesenchymal stem cell/human umbilical vein endothelial cell (HBMSC/HUVEC) co-spheroids.
- To investigate the efficacy of colloidal self-assembled patterns (cSAPs) for spheroid formation.
- To evaluate the osteogenic and angiogenic potential of these co-spheroids within a phenol-modified gelatin/hyaluronan (Gel-Ph/HA-Ph) hydrogel system.
Main Methods:
- Preparation of HBMSC/HUVEC co-spheroids using cSAPs, a superior nanopatterning technique.
- Encapsulation of multicellular spheroids in Gel-Ph/HA-Ph hydrogels, photo-crosslinked with blue light.
- Assessment of osteogenic differentiation markers (Runx2, ALP, Col1a1, OPN) and vascular network formation (CD31+ cells) in vitro.
- In vivo evaluation of angiogenesis and blood vessel development in a subcutaneous nude mouse model.
Main Results:
- Gel-Ph/HA-Ph hydrogels exhibited optimal properties at a 5%-to-0.3% ratio.
- HBMSC/HUVEC co-spheroids showed significantly enhanced osteogenic differentiation compared to HBMSC spheroids.
- Co-spheroids demonstrated improved vascular network formation in vitro and superior angiogenesis in vivo.
- cSAPs proved more effective than low-adhesion surfaces for spheroid generation.
Conclusions:
- The combination of cSAPs, cell coculturing, and hydrogel technology offers a promising approach for generating and applying multicellular spheroids.
- HBMSC/HUVEC co-spheroids exhibit superior potential for bone regeneration and vascularization applications.
- This study provides a novel platform for studying complex cell interactions in 3D tissue engineering constructs.
