De novo design of functional coassembling organic−inorganic hydrogels for hierarchical mineralization and neovascularization

Okesola, Babatunde O. and Mendoza-Martinez, Ana Karen and Cidonio, Gianluca and Derkus, Burak and Boccorh, Delali K. and Osuna de la Peña, David and Elsharkawy, Sherif and Wu, Yuanhao and Dawson, Jonathon I. and Wark, Alastair W. and Knani, Dafna and Adams, Dave J. and Oreffo, Richard O. C. and Mata, Alvaro (2021) De novo design of functional coassembling organic−inorganic hydrogels for hierarchical mineralization and neovascularization. ACS Nano, 15 (7). pp. 11202-11217. ISSN 1936-0851 (

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Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful, and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite, Lap) and peptide amphiphiles (PAs, PAH3) rationally designed to coassemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessed to confirm that PAH3 nanofibers electrostatically adsorbed and conformed to the surface of Lap nanodisks. Electron and atomic force microscopies also confirmed an increase in diameter and surface area of PAH3 nanofibers after coassembly with Lap. Dynamic oscillatory rheology revealed that the coassembled PAH3-Lap hydrogels displayed high stiffness and robust self-healing behavior while gas adsorption analysis confirmed a hierarchical and heterogeneous porosity. Furthermore, this distinctive structure within the three-dimensional (3D) matrix provided spatial confinement for the nucleation and hierarchical organization of high-aspect ratio hydroxyapatite nanorods into well-defined spherical clusters within the 3D matrix. Applicability of the organic–inorganic PAH3-Lap hydrogels was assessed in vitro using human bone marrow-derived stromal cells (hBMSCs) and ex vivo using a chick chorioallantoic membrane (CAM) assay. The results demonstrated that the organic–inorganic PAH3-Lap hydrogels promote human skeletal cell proliferation and, upon mineralization, integrate with the CAM, are infiltrated by blood vessels, stimulate extracellular matrix production, and facilitate extensive mineral deposition relative to the controls.


Okesola, Babatunde O., Mendoza-Martinez, Ana Karen, Cidonio, Gianluca, Derkus, Burak, Boccorh, Delali K., Osuna de la Peña, David, Elsharkawy, Sherif, Wu, Yuanhao, Dawson, Jonathon I., Wark, Alastair W. ORCID logoORCID:, Knani, Dafna, Adams, Dave J., Oreffo, Richard O. C. and Mata, Alvaro;