Material strategies for creating artificial cell-instructive niches

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There has been a tremendous growth in the use of biomaterials serving as cellular scaffolds for tissue engineering applications. Recently, advanced material strategies have been developed to incorporate structural, mechanical, and biochemical signals that can interact with the cell and the in vivo environment in a biologically specific manner. In this article, strategies such as the use of composite materials and material processing methods to better mimic the extracellular matrix, integration of mechanical and topographical properties of materials in scaffold design, and incorporation of biochemical cues such as cytokines in tethered, soluble, or time-released forms are presented. Finally, replication of the dynamic forces and biochemical gradients of the in vivo cellular environment through the use of microfluidics is highlighted.

Highlights

► Biomaterial selection based on origin, biodegradability, and microstructure. ► Bulk and surface biochemical modification of scaffolds for presentation of cytokines. ► Designing scaffolds with in vivo-like mechanical properties and topography. ► Use of microfluidics to replicate dynamic mechanical and biochemical parameters.

Introduction

In the engineering of tissues, a scaffold is often required to provide an environment or niche that favors the natural behavior of cells. This scaffold must fulfill a wide range of requirements, from physical and biochemical to cellular parameters [1, 2]. These requirements have stemmed from the notion that mimicking the extracellular environment—its structure, mechanical and biochemical properties—in designing cellular scaffolds, will coax cells to behave in the same manner as their in vivo counterparts. Engineering of such scaffolds requires close attentiveness to several material design criteria: (i) the 3-dimensional (3D) micro-geometry within the scaffold including porosity, pore size, and interpore connectivity to satisfy adequate mass transfer of gases, nutrients, and waste as well as cell attachment and spreading, and tissue formation; (ii) mechanical parameters such as linearity or non-linearity, elasticity, viscoelasticity, or anisotropy that must be tailored to the specific tissue in mind; and (iii) successful delivery of biologics including cells, nucleic acids, and cytokines. In this review, these three material design criteria will be discussed, methods utilized to mimic the in vivo cell microenvironment will be highlighted, and recent research contributing to better bioactive scaffold fabrication using advanced material strategies will be presented (Figure 1). Such materials can either directly alter the cellular differentiation pathways or be used as permissive environments for approaches in which the cell phenotype is altered using ‘pathway engineering’ approaches. An example of the latter approach is to develop advanced materials that enable the generation of induced pluripotent stem cells [3].

Section snippets

Creating the cellular scaffold

In choosing the material to be used for a scaffold, a wide range of options exists—natural and synthetic materials, and composites of two or more from the same class or different classes of materials; the advantages and disadvantages of using that material must be known, in addition to its suitability for the desired application. Naturally-derived materials are often purified extracellular matrix (ECM) proteins (collagen, gelatin [4], laminin, hyaluronic acid) or a mixture (Matrigel®). Other

Mimicking the physical aspects of the cell's microenvironment

The physical aspects of the cell's microenvironment can be broken down into substrate mechanics and surface topography. Depending on their anatomical location, tissues have a wide range of mechanical properties. For instance, the elastic moduli of brain (0.5 kPa) is relatively soft compared to muscles and skin (about 10 kPa) and precalcified bone (>30 kPa) [25]. Another challenge in recreating the native cellular environment is that many tissues are viscoelastic with non-linear, anisotropic, and

Biochemical modulation of materials

To generate cell-instructive scaffolds, it is necessary to encode them with biological information. In vivo, this information is in the form of signaling molecules or cytokines, in tethered or freely soluble forms. Currently, the material strategies for presenting cytokines within scaffolds include covalent attachment, adsorption, and use of controlled-release particles [40]. One of the initial steps after seeding cells on or into a scaffold is integrin-mediated cell attachment. Hence, covalent

Moving from static to dynamic environments

In the in vivo microenvironment, a dynamic interplay exists between cells and biochemical and physical cues that currently cannot be controlled in standard in vitro models. Microfluidics, a field involving the manipulation of fluids at the micron-scale dimension, has made it possible to replicate the dynamic in vivo conditions in in vitro models [50, 51]. Commonly used materials in microfluidic devices include poly(dimethylsiloxane) or polyesters that may be undesirable given their

Future outlooks

Advanced material strategies stemming from materials science, physics, chemistry, and biology have heralded a new era in the design of tissue engineering scaffolds whereby the biochemical, mechanical, and structural details of a cell's microenvironment or niche can be replicated to influence cell behaviors such as gene expression, adhesion, migration, and differentiation. However, more work needs to be done to understand the properties of native tissues, to define proper mechanical

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The authors acknowledge funding from the National Science Foundation CAREER Award (DMR 0847287), the office of Naval Research Young National Investigator Award, and the National Institutes of Health (HL092836, DE019024, EB012597, AR057837, DE021468, HL099073, EB008392).

References (64)

  • X. Wang et al.

    Growth factor gradients via microsphere delivery in biopolymer scaffolds for osteochondral tissue engineering

    J Control Release

    (2009)
  • X. Zhao et al.

    Active scaffolds for on-demand drug and cell delivery

    Proc Natl Acad Sci USA

    (2011)
  • D.A. Wang et al.

    Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration

    Nat Mater

    (2007)
  • E. Choi et al.

    Quantitatively controlled in situ formation of hydrogel membranes in microchannels for generation of stable chemical gradients

    Lab Chip

    (2012)
  • S.J. Hollister

    Scaffold design and manufacturing: from concept to clinic

    Adv Mater

    (2009)
  • F. Edalat et al.

    Engineering approaches toward deconstructing and controlling the stem cell environment

    Ann Biomed Eng

    (2012)
  • Y.-C. Chen et al.

    Functional human vascular network generated in photocrosslinkable gelatin methacrylate hydrogels

    Adv Funct Mater

    (2012)
  • C. Quint et al.

    Decellularized tissue-engineered blood vessel as an arterial conduit

    Proc Natl Acad Sci USA

    (2011)
  • H.C. Ott et al.

    Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart

    Nat Med

    (2008)
  • T.H. Petersen et al.

    Tissue-engineered lungs for in vivo implantation

    Science

    (2010)
  • B.E. Uygun et al.

    Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix

    Nat Med

    (2010)
  • W.L. Grayson et al.

    Engineering anatomically shaped human bone grafts

    Proc Natl Acad Sci USA

    (2010)
  • J. Zhu

    Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering

    Biomaterials

    (2010)
  • S.R. Shin et al.

    Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation

    ACS Nano

    (2012)
  • S. Namgung et al.

    Controlling the growth and differentiation of human mesenchymal stem cells by the arrangement of individual carbon nanotubes

    ACS Nano

    (2011)
  • J.O. You et al.

    Nanoengineering the heart: conductive scaffolds enhance connexin 43 expression

    Nano Lett

    (2011)
  • G. Cellot et al.

    Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts

    Nat Nanotechnol

    (2009)
  • T.P. Kraehenbuehl et al.

    Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel

    Biomaterials

    (2008)
  • N. Annabi et al.

    Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro

    Biomaterials

    (2009)
  • T.J. Sill et al.

    Electrospinning: applications in drug delivery and tissue engineering

    Biomaterials

    (2008)
  • B.V. Slaughter et al.

    Hydrogels in regenerative medicine

    Adv Mater

    (2009)
  • S. Nemir et al.

    Synthetic materials in the study of cell response to substrate rigidity

    Ann Biomed Eng

    (2010)

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