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  • Review Article
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Building drug delivery into tissue engineering design

Nature Reviews Drug Discovery volume 1, pages 177–186 (2002)Cite this article

Key Points

  • The engineering of many tissue structures, such as the branching architectures that are found in many tissues, or the intricate network architecture of the nervous system, will require new methods for producing controlled spatial and temporal gradients of agents in developing tissues.

  • Controlled-release technology has many direct applications to tissue engineering; for example, local delivery of growth factors can be accomplished by encapsulating the agent within a biocompatible polymer matrix or microsphere.

  • Controlled growth-factor delivery systems can also be used in conjugation with biocompatible matrices or porous scaffolds that provide morphological guides for the assembly of regenerating tissue within a controllable microenvironment.

  • Microfluidic devices, which are composed of networks of interconnected channels, pumps, valves, mixers and separators, will be useful in developing new tools for drug delivery and tissue engineering, including the microfluidic control of cell positioning and local agent delivery.

  • In tissue engineering, the transformation of a neotissue into a functional replacement tissue occurs in a series of steps, in which each step potentially involves different biological signals that can be introduced by controlled delivery methods.

  • Modelling the dynamics of agent diffusion and convection at local tissue sites will be an essential tool for developing new delivery systems that provide spatial and temporal control over agent delivery.

Abstract

The creation of efficient methods for manufacturing biotechnology drugs — many of which influence fundamental but complex cell behaviours, such as proliferation, migration and differentiation — is creating new opportunities for tissue repair. Many agents are potent and multifunctional; that is, they produce different effects within different tissues. Therefore, control of tissue concentration and spatial localization of delivery is essential for safety and effectiveness. Synthetic systems that can control agent delivery are particularly promising as materials for enhancing tissue regeneration. This review discusses the state of the art in controlled-release and microfluidic drug delivery technologies, and outlines their potential applications for tissue engineering.

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Figure 1: Methods for controlled delivery of agents into localized regions of tissue.
Figure 2: Surface gradients of agents.
Figure 3: Dynamics of NGF delivery to a localized region of tissue.
Figure 4: Concentration gradients produced by controlled-release systems.
Figure 5: Flow in a microfluidic channel.
Figure 6: Penetration of agents that are delivered by diffusion or convection.

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Acknowledgements

We thank M. Isaacson, S. Retterer and A. Spence for helpful discussions and for providing images. Our work on NGF delivery system is supported by the National Institutes for Health.

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  1. School of Chemical Engineering, Cornell University, 120 Olin Hall, Ithaca, 14853, New York, USA

    W. Mark Saltzman & William L. Olbricht

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Correspondence to W. Mark Saltzman.

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DATABASES

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BDNF

rhBMP2

EGF

FGF2

FGF8

β-glucuronidase

NGF

NT3

PDGF

TGF-β

VEGF

 Medscape DrugInfo

cyclosporine

FURTHER INFORMATION

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Glossary

NEOTISSUE

An assembly of cellular, protein and synthetic elements, in which the various components are physically arranged to encourage development into a functional replacement tissue.

CHONDROCYTE

A cartilage cell.

MORPHOGEN

A biological agent, often a protein, that influences a change in cell behaviour.

NORPLANT

A cylindrical silicone implant loaded with contraceptive steriods, which provides constant steroid release for up to five years.

GLIADEL

This consists of biodegradable wafers of polyanhydride loaded with a chemotherapy drug, which can be implanted in the brain for local, controlled release at a tumour re-section site.

ELECTRO-OSMOSIS

The motion of a liquid, relative to a stationary charged surface, which is induced by an applied electric field.

PIEZOELECTRIC

A property of certain materials — for example, quartz — that produces a physical deformation that is proportional to an applied potential difference.

ELECTROKINETIC

This describes various phenomena that involve the motion of fluids that contain charged particles or ions in electric fields.

OHMIC HEATING

The generation of heat due to the passage of an electrical current through a medium with electrical resistance.

REYNOLDS NUMBER

A dimensionless number, the value of which estimates the relative importance of inertial forces compared with viscous forces in flowing fluids.

ANISOTROPIC ETCHING

An etching process that exploits the crystalline structure of certain materials, such as silicon, to etch at different rates in different directions.

BICOID PROTEIN

A transcription-factor protein that is produced in Drosophila melanogaster by a maternal-effect gene; messenger RNA from the maternal gene is segregated to the anterior pole of the developing egg, resulting in spatially localized synthesis of Bicoid protein.

PHARMACOTECTONIC

This describes techniques that allow control of the spatial positioning of agents in a tissue or organ.

DARCY'S LAW

An empirical statement that the volumetric flow rate in a porous medium is linearly proportional to the applied pressure gradient.

PECLET NUMBER

A dimensionless number, the value of which estimates the relative importance of mass transfer by convection compared with mass transfer by diffusion.

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Saltzman, W., Olbricht, W. Building drug delivery into tissue engineering design. Nat Rev Drug Discov 1, 177–186 (2002). https://doi.org/10.1038/nrd744

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