Manipulating Stem Cell Fate with Disordered Bioactive Cues on Surfaces: The Role of Bioactive Ligand Selection

Yujie Zhang, Murielle Remy, Thierry Leste-Lasserre, Marie-Christine Durrieu
ACS Appl. Mater. Interfaces. 2024-04-06; :
DOI: 10.1021/acsami.4c00262

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Zhang Y(1), Remy M(1), Leste-Lasserre T(2), Durrieu MC(1).

Author information:
(1)CNRS, Bordeaux INP, CBMN, Univ. Bordeaux, UMR 5248, Pessac33600,France.
(2)INSERM, PUMA, U1215, Neurocentre Magendie, Univ. Bordeaux,

The development of 2D or 3D bioactive platforms for rapidly isolating pure
populations of cells from adult stem cells holds promise for advancing the
understanding of cellular mechanisms, drug testing, and tissue engineering. Over
the years, methods have emerged to synthesize bioactive micro- and
nanostructured 2D materials capable of directing stem cell fate. We introduce a
novel method for randomly micro- or nanopatterning any protein/peptide onto both
2D and 3D scaffolds via spray technology. Our goal is to investigate the impact
of arranging bioactive micropatterns (ordered vs disordered) on surfaces to
guide human mesenchymal stem cell (hMSC) differentiation. The spray technology
efficiently coats materials with controlled, cost-effective bioactive
micropatterns in various sizes and shapes. BMP-2 mimetic peptides were
covalently grafted, individually or in combination with RGD peptides, onto
activated polyethylene terephthalate (PET) surfaces through a spraying process,
incorporating nano/microscale parameters like size, shape, and composition. The
study explores different peptide distributions on surfaces and various peptide
combinations. Four surfaces were homogeneously functionalized with these
peptides (M1 to M4 with various densities of peptides), and six surfaces with
disordered micro- and nanopatterns of peptides (S0 to S5 with different sizes of
peptide patterns) were synthesized. Fluorescence microscopy assessed peptide
distribution, followed by hMSC culture for 2 weeks, and evaluated osteogenic
differentiation via immunocytochemistry and RT-qPCR for osteoblast and osteocyte
markers. Cells on uniformly peptide-functionalized surfaces exhibited cuboidal
forms, while those on surfaces with disordered patterns tended toward columnar
or cuboidal shapes. Surfaces S4 and S5 showed dendrite-like formations
resembling an osteocyte morphology. S5 showed significant overexpression of
osteoblast (OPN) and osteocyte markers (E11, DMP1, and SOST) compared to control
surfaces and other micropatterned surfaces. Notably, despite sharing an
equivalent quantity of peptides with a homogeneous functionalized surface, S5
displayed a distinct distribution of peptides, resulting in enhanced osteogenic
differentiation of hMSCs.


Auteurs Bordeaux Neurocampus