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Morphogenesis Guided by 3D Patterning of Growth Factors in Biological Matrices
Author(s) -
Broguiere Nicolas,
Lüchtefeld Ines,
Trachsel Lucca,
Mazunin Dmitry,
Rizzo Riccardo,
Bode Jeffrey W.,
Lutolf Matthias P.,
ZenobiWong Marcy
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201908299
Subject(s) - biomolecule , self healing hydrogels , materials science , sortase , morphogenesis , nanotechnology , regeneration (biology) , extracellular matrix , surface modification , biophysics , microbiology and biotechnology , chemistry , biology , biochemistry , bacterial protein , polymer chemistry , gene
Abstract Three‐dimensional (3D) control over the placement of bioactive cues is fundamental to understand cell guidance and develop engineered tissues. Two‐photon patterning (2PP) provides such placement at micro‐ to millimeter scale, but nonspecific interactions between proteins and functionalized extracellular matrices (ECMs) restrict its use. Here, a 2PP system based on nonfouling hydrophilic photocages and Sortase A (SA)‐based enzymatic coupling is presented, which offers unprecedented orthogonality and signal‐to‐noise ratio in both inert hydrogels and complex mammalian matrices. Improved photocaged peptide synthesis and protein functionalization protocols with broad applicability are introduced. Importantly, the method enables 2PP in a single step in the presence of fragile biomolecules and cells, and is compatible with time‐controlled growth factor presentation. As a corollary, the guidance of axons through 3D‐patterned nerve growth factor (NGF) within brain‐mimetic ECMs is demonstrated. The approach allows for the interrogation of the role of complex signaling molecules in 3D matrices, thus helping to better understand biological guidance in tissue development and regeneration.