De Novo Design of Functional Coassembling Organic-Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization.

Babatunde O Okesola,Burak Derkus,Gianluca Cidonio,Sherif Elsharkawy,Jonathan I Dawson,Ana Karen Mendoza-Martinez,Dafna Knani,David Osuna De La Peña,Alastair W Wark,Richard O C Oreffo,Yuanhao Wu,Dave J Adams,Delali K Boccorh,Alvaro Mata

doi:10.1021/acsnano.0c09814

Abstract

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.

Highlights

Nature contains an array of functional nanomaterials that result from the supramolecular coassembly of organic and inorganic building blocks across multiple length scales
Based on the pioneering work of Aida and coworkers on coassembling Lap nanodisks with guanidiniumbased dendritic binders,[48] we hypothesized that our PAH3Lap coassembling system would generate mechanically reinforced organic−inorganic hydrogels
We have developed a coassembling organic−inorganic hydrogel platform for in vitro crystal growth mediated by a particle attachment mechanism within a 3D supramolecular confined framework

Summary

Introduction

Nature contains an array of functional nanomaterials that result from the supramolecular coassembly of organic and inorganic building blocks across multiple length scales Materials such as tooth enamel, bones, nacre from mollusc shells, and marine diatom frustules exhibit a high level of precision over their molecular composition, hierarchical structure, and morphology. The inherent characteristics endow these nanomaterials with properties ranging from high stiffness to light-emission.[1,2] A fundamental characteristic of natural organic−inorganic composites is the presence of organic matrixes exhibiting ordered arrays of confined charged groups, which induce and regulate the spatial nucleation and hierarchical organization of crystals.[3,4] These organic components are generally 3D hydrogel-like materials made from multiple components such as proteins, peptides, polyamines, and polysaccharides.[5,6].

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