Multifunctional and Continuous Gradients of Biointerfaces Based on Dual Reverse Click Reactions

Abstract

Chemical or biological gradients that are composed of multifunctional and/or multidirectional guidance cues are of fundamental importance for prospective biomaterials and biointerfaces. As a proof of concept, a general modification approach for generating multifunctional and continuous gradients was realized via two controlled and reversed click reactions, namely, thermo-activated thiol-yne and copper-free alkyne and azide click reactions. The cell adhesion property of fibroblasts was guided in a gradient with an enhancement, showing that the PEG molecule and RGD peptide were countercurrently immobilized to form such reversed gradients (with negating of the cell adhesion property). Using the gradient modification protocol to also create countercurrent distributions of FGF-2 and BMP-2 gradients, the demonstration of not only multifunctional but also gradient biointerfacial properties was resolved in time latencies on one surface by showing the manipulation in gradients toward proliferation and osteogenic differentiation for adipose-derived stem cells.

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

“…Biofunctionalization of biomaterial surfaces have demonstrated good results toward the induction of different phenotypes in single structures. Multifunctional gradients using controllable and reversed click reactions [72] or polymerization of dopamine [73,74] have been explored for tendon-bone interface regeneration. Resulting available groups provide accessibility for biomolecule immobilization and biomineralization [74], allowing a gradual differentiation of stem cells ( Figure 3C).…”

“…After 21 days with human adipose tissue-derived stem cells (ASCs) in functionalized surfaces with BMP2 and FGF-2, a gradient was observed of (iii) ALP expression, (iv) calcium deposition, and (v) osteocalcin expression, showing the osteogenic commitment of hASCs in a continuous and gradient manner. Reproduced, with permission, from [72]. Abbreviations: rBMSC: rat bone marrow mesenchymal stem cells.…”

Biphasic Hydrogels Integrating Mineralized and Anisotropic Features for Interfacial Tissue Engineering

“…Despite the optimal combination of these biochemical factors is not fully understood, the gradual combination of bone morphogenetic protein 2 with fibroblast growth factor 2 57 or transforming growth factor β2 with growth/differentiation factor 5 58 have led to promising results. Although the evaluation of the incorporation of specific growth factors was beyond the scope of this work, the transglutaminase enzyme proposed in this research work presents the potential to support the covalent immobilization and the required sustained release of growth factors 59,60,60 .…”

Micro- and nano-surface structures based on vapor-deposited polymers

“…The two-click reactions were employed to co-immobilize fibroblast growth factor 2 (FGF-2) and bone morphogenetic protein 2 (BMP-2) and established reverse gradient distributions of the FGF-2 and BMP-2. Furthermore, these two growth factors gradients have demonstrated the corresponding biological activities toward both proliferation (FGF-2) and osteogenic differentiation (BMP-2) for adipose-derived stem cells [ 76 ].…”