Review
Nanoscale engineering of extracellular matrix-mimetic bioadhesive surfaces and implants for tissue engineering

https://doi.org/10.1016/j.bbagen.2010.04.006Get rights and content

Abstract

Background

The goal of tissue engineering is to restore tissue function using biomimetic scaffolds which direct desired cell fates such as attachment, proliferation and differentiation. Cell behavior in vivo is determined by a complex interaction of cells with extracellular biosignals, many of which exist on a nanoscale. Therefore, recent efforts in tissue engineering biomaterial development have focused on incorporating extracellular matrix- (ECM) derived peptides or proteins into biomaterials in order to mimic natural ECM. Concurrent advances in nanotechnology have also made it possible to manipulate protein and peptide presentation on surfaces on a nanoscale level.

Scope of Review

This review discusses protein and peptide nanopatterning techniques and examples of how nanoscale engineering of bioadhesive materials may enhance outcomes for regenerative medicine.

Major Conclusions

Synergy between ECM-mimetic tissue engineering and nanotechnology fields can be found in three major strategies: (1) Mimicking nanoscale orientation of ECM peptide domains to maintain native bioactivity, (2) Presenting adhesive peptides at unnaturally high densities, and (3) Engineering multivalent ECM-derived peptide constructs.

General Significance

Combining bioadhesion and nanopatterning technologies to allow nanoscale control of adhesive motifs on the cell–material interface may result in exciting advances in tissue engineering.

This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.

Section snippets

Tissue engineering and biomimetic strategies overview

The main goal of tissue engineering and regenerative medicine strategies is to restore the function of damaged tissues by delivering a combination of cells, biological factors and a biomaterial scaffold on which these cells must adhere, organize and develop similarly to native tissue (Fig. 1). In vivo, cell fates are determined by a complex interaction of nanoscale physical and chemical signals. Therefore, scaffolds for tissue engineering often incorporate biosignals to create a controlled,

Cellular interactions with extracellular environment

Signals from the extracellular microenvironment that may be incorporated into biomaterials (Fig. 2) fall into three major categories: (1) insoluble extracellular matrix (ECM) macromolecules, (2) diffusible/soluble molecules, and (3) cell–cell receptors.

From micro to nano in biomaterials

Over the past few decades, techniques for creating nanoscale features, patterns and particles have emerged. Although these techniques were initially applied to electronics fabrication, they have more recently been used to pattern and immobilize proteins and peptides with nanoscale precision for applications such as tissue engineering, drug delivery and biosensing. Like nanotechnology, the interdisciplinary field of tissue engineering is also fledgling, and began approximately two decades ago

Techniques to nanopattern peptides and proteins

Nanoscale control of ECM-derived peptides and proteins have primarily been used for non-regenerative medicine applications, including biosensing, drug delivery and for model systems to study cell functions such as adhesion and spreading. However, given that integrins and focal adhesions exist on submicron size scales, there is a compelling rationale for using nanotechnology in bioadhesive tissue engineering applications. The following strategies have been used to control and pattern proteins

Nanoscale engineering of proteins and peptides for bioadhesion

How can nanoscale engineering of ECM-derived adhesive peptides be used to enhance cellular response for tissue regeneration? Although this field is admittedly in its infancy, some significant works have already been completed which demonstrate the promise of this approach. Nanoscale bioadhesive tissue engineering strategies which have been employed can be classified under three major categories:

  • 1)

    Nanoscale control of adhesive and modulatory peptide domains to retain full bioactivity of parental

Conclusion and future outlook

The fast-evolving fields of tissue engineering and nanotechnology have begun to converge, giving rise to new methods of directing cell fates by controlling the presentation of ECM-derived peptides with nanoscale precision. In recent decades, a range of exciting new strategies for peptide nanopatterning have been developed with important benefits and capabilities such as patterning more complex, higher resolution, multi-peptide patterns with greater spatial control, as well as rapid and low-cost

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