Biomedical Engineering Reference
In-Depth Information
7.1
Chapter 7.1
Tissue engineering
Simon P. Hoerstrup, Lichun Lu, Michael J. Lysaght, Antonios G. Mikos, David Rein,
Frederick J. Schoen, Johnna S. Temenoff, Joerg K. Tessmar, and Joseph P. Vacanti
engineering
and
biological
principles
specifically
for
7.1.1 Introduction
medical application (
Bokros, 1977
).
Subsequently, technology enabled and certain appli-
cations benefited by ''second-generation'' biomaterials
that were intended to elicit a nontrivial and controlled
reaction with the tissues into which they were im-
planted, in order to induce a desired therapeutic advan-
tage. In the 1980s,
bioactive
materials were in clinical use
in orthopedic and dental surgery as various compositions
of bioactive glasses and ceramics (
Hench and Pollak,
2002
), in controlled-localized drug release applications
such as the Norplant hormone-loaded contraceptive
formulation, and in devices such as the HeartMate
left
ventricular assist device for patients with congestive
heart failure, with an integrally-textured polyurethane
surface that fosters a controlled thrombotic reaction to
minimize the risk of thromboembolism (
Rose
et al.
,
2001
). Recently, drug-eluting endovascular stents have
been shown to markedly limit in-stent proliferative
restenosis following balloon angioplasty (Sousa
et al.,
2003). The need for maximally effective dosing regi-
mens, new protein-and nucleic acid-based drugs (which
cannot be taken in classical pill form), and elimination of
systemic toxicities have stimulated development of new
implantable polymers and innovative systems for con-
trolled drug delivery and gene therapy (La
Va n
et al.
,
2002
). Controlled drug delivery is now capable of pro-
viding a wide range of drugs that can be targeted (e.g., to
a tumor, to a diseased blood vessel, to the pulmonary
alveoli) on a one-time or sustained basis with highly reg-
ulated dosage and can regulate cell and tissue responses
through delivery of growth factors and plasmid DNA
containing genes that encode growth factors (Bonadio
et al.
,1999;
Richardson
et al.
, 2001
).
Frederick J. Schoen
Biomaterials investigation and development has been
stimulated and informed by a logical evolution of cell and
molecular biology, materials science, and engineering,
and an understanding of the interactions of materials
with the physiological environment. These developments
have permitted the evolution of concepts of tissue-
biomaterials interactions to evolve through three stages,
overlapping over time, yet each with a distinctly different
objective (
Fig. 7.1.1-1
)(
Hench and Pollak, 2002
). The
logical and rapidly progressing state-of-the-art, called
tissue engineering,
is discussed in this chapter.
The goal of early biomaterials development and use in
a wide variety of applications was to achieve a suitable
combination of functional properties to adequately
match those of the replaced tissue without deleterious
response by the host. The ''first generation'' of modern
biomaterials (beginning in the mid-20th century) used
largely off-the-shelf, widely available, industrial materials
that were not developed specifically for their intended
medical use. They were selected because of a desirable
combination of physical properties specific to the clinical
use, and they were intended to be
bioinert
(i.e., they
elicited minimal response from the host tissues). The
widely used elastomeric polymer silicone rubber is pro-
totypical. Pyrolytic carbon, originally developed in the
1960s as a coating material for nuclear fuel particles and
now widely used in mechanical heart valve substitutes,
exemplifies one of the first biomaterials whose formula-
tion was studied, modified, and controlled according to
