Molecular Imprinting Strategies for Tissue Engineering Applications: A Review

Abstract

Tissue Engineering (TE) represents a promising solution to fabricate engineered constructs able to restore tissue damage after implantation. In the classic TE approach, biomaterials are used alongside growth factors to create a scaffolding structure that supports cells during the construct maturation. A current challenge in TE is the creation of engineered constructs able to mimic the complex microenvironment found in the natural tissue, so as to promote and guide cell migration, proliferation, and differentiation. In this context, the introduction inside the scaffold of molecularly imprinted polymers (MIPs)-synthetic receptors able to reversibly bind to biomolecules-holds great promise to enhance the scaffold-cell interaction. In this review, we analyze the main strategies that have been used for MIP design and fabrication with a particular focus on biomedical research. Furthermore, to highlight the potential of MIPs for scaffold-based TE, we present recent examples on how MIPs have been used in TE to introduce biophysical cues as well as for drug delivery and sequestering.

Keywords: molecularly imprinted polymers; scaffolds; tissue engineering.

Figure 1

Main elements and fabrication steps to produce a molecularly imprinted polymer. During the pre-polymerization step, different chemical bonds may form between the template molecule and functional monomers. In the semi-covalent case, covalent bonds are cleaved after polymerization, leaving accessible binding sites inside the MIP. During the rebinding step, the template interacts with these sites using non-covalent interactions.

Figure 2

Simplified schematics of the micro-contact printing procedure for proteins.

Figure 3

An example of EI for the selective capture and release of cancer cells. In (a), a schematic representation of the process. The SA epitope is imprinted over the surface of the PNIPAAm hydrogel; at 37 °C, the epitope is exposed on the surface, so that cancer cells can bind to it. When lowering the temperature to 25 °C, the conformational changes in the thermo-responsive hydrogel cause the cell release, since the SA group is no longer exposed. In (b), the efficiency of the cell capture-and-release method, expressed in terms of the cell number, while in (c) the capture profile over time compared to the non-imprinted hydrogel (NIH). Finally, in (d) the staining of the cell on the hydrogel surface at 37 °C (captured cells) and 25 °C (released cells). Figure modified with permission from [83].

Figure 4

Cell MI to create physical cues able to guide cell activities. In (A), ALP activity and calcium deposition measured at 7 and 14 days for osteoblast-like cells culture on smooth PDMS surface, and on PDMS surface imprinted with the same cell type after different culturing times (4 h, 7 days and 14 days). Image reprinted with permission from [90]. In (B), atomic force microscope images of ADSCs cells cultured on a keratinocytes-imprinted and ADSCs-imprinted silicone substrate. Image reprinted with permission from [100]. In (C), profilometry images of the PDMS substrates imprinted with different cell types (chondrocytes, tenocytes and ADSCs), alongside the gene expression results of different cell cultures on the substrates (specifically, (a,b) ADSCs, (c) fibroblasts and (d) tenocytes). Image reprinted with permission from [101].