Biomaterials for the Treatment of Myocardial Infarction
Karen L. Christman, and Randall J. Lee
J. Am. Coll. Cardiol. 2006;48;907-913; originally published online Aug 15, 2006;
doi:10.1016/j.jacc.2006.06.005
This information is current as of March 6, 2010
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://content.onlinejacc.org/cgi/content/full/48/5/907
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Journal of the American College of Cardiology Vol. 48, No. 5, 2006
© 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2006.06.005
STATE-OF-THE-ART PAPERS
Biomaterials for the
Treatment of Myocardial Infarction
Karen L. Christman, PHD,* Randall J. Lee, MD, PHD* !
Berkeley and San Francisco, California
For nearly a decade, researchers have investigated the possibility of cell transplantation for
cardiac repair. More recently, the emerging fields of tissue engineering and biomaterials have
begun to provide potential treatments. Tissue engineering approaches are designed to repair
lost or damaged tissue through the use of growth factors, cellular transplantation, and
biomaterial scaffolds. There are currently 3 biomaterial approaches for the treatment of
myocardial infarction (MI). The first involves polymeric left ventricular restraints in the
prevention of heart failure. The second utilizes in vitro engineered cardiac tissue, which is
subsequently implanted in vivo. The final approach entails injecting cells and/or a scaffold into
the myocardium to create in situ engineered cardiac tissue. This review gives an overview of
the current progress in the growing field of biomaterials for the treatment of MI. (J Am
Coll Cardiol 2006;48:907 13) © 2006 by the American College of Cardiology Foundation
Heart failure after a myocardial infarction (MI) is often LV RESTRAINTS
progressive. After death of the cardiomyocytes, macrophages,
To prevent the negative LV remodeling and LV dilation
monocytes, and neutrophils migrate into the infarct area,
associated with MI (2), many studies have examined the use
initiating the inflammatory response. Infarct expansion then
of biomaterial supports to restrain the LV. Kelley et al. (3)
begins to occur because of the activation of matrix metallopro-
first demonstrated that restraining infarct expansion pre-
teases (MMPs), which degrade the extracellular matrix and
vents a decline in cardiac function after an anteroapical MI.
result in myocyte slippage. This weakening of the collagen
A poly(propylene) (Marlex) mesh was sutured onto the
scaffold results in wall thinning and ventricular dilation. After
myocardium at the location of a subsequently induced MI.
the initial inflammatory phase, there is an increase in fibrillar,
Restraining the infarct wall preserved both LV geometry
cross-linked collagen deposition, which resists deformation
and cardiac function. Moreover, Bowen et al. (4) demon-
and rupture (1). Evidence suggests that the death of cardio-
strated that the poly(propylene) restraint increased collagen
myocytes results in negative left ventricular (LV) remodeling,
and reduced MMP-1 and -2 activity in the border-zone
which leads to increased wall stress in the remaining viable
myocardium; however, both matrix components were un-
myocardium. This process results in a sequence of molecular,
changed within the infarct. Although Moainie et al. (5)
cellular, and physiological responses that lead to LV dilation. It
reported reduced ischemic mitral regurgitation in a postero-
is suggested that LV remodeling may contribute independently
lateral MI model, the LV volume of animals treated with
to the progression of heart failure (2).
the Marlex mesh was not statistically different from control
Cellular transplantation, LV restraint devices, and tissue
animals. A Marlex mesh covering the infarcted area was also
engineering approaches have emerged as possible alternatives
compared to a Merselene (knitted polyester) mesh that
to heart transplantation for the treatment of damaged myocar-
wrapped around the LV. Enomoto et al. (6) reported that
dium (Fig. 1). Initial studies focused on the injection of viable
wrapping of the LV improved remodeling compared to the
cells directly into the infarcted myocardium, a technique which
mesh, which covered only the infarcted area, indicating that
has been termed cellular cardiomyoplasty. More recent ap-
stiffening only the infarct may not be sufficient.
proaches include the use of in vitro engineered tissue, which is
cultured in vitro and then implanted in vivo, and in situ engi- Another type of LV restraint consisting of a knitted
polyester mesh has been developed by Acorn Cardiovascular
neered tissue, which is injected directly into the myocardium.
Polymer meshes have also been utilized to prevent LV expan- Inc. (St. Paul, Minnesota) The cardiac support device
(CSD), which is fitted around both ventricles, was shown to
sion. This review focuses on the current advances and progress
in the use biomaterials for treatment of MI (Table 1). Bioma- decrease LV end-diastolic volume, myocyte hypertrophy,
terial treatments that have been examined in vivo are covered. and interstitial fibrosis, as well as increase fractional short-
ening, in a study by Chaudhry et al. (7) using a canine
chronic heart failure model. Saavedra et al. (8) further
From the *University of California-Berkeley and San Francisco Joint Bioengineer-
demonstrated that the CSD induced reverse remodeling, as
ing Graduate Group, Berkeley and San Francisco, California; and the Department
of Medicine and ! Cardiovascular Research Institute, University of California-San
indicated by decreased LV volume and a shifted end-systolic
Francisco, San Francisco, California.
pressure-volume relation. Pilla et al. (9) also showed a
Manuscript received December 19, 2005; revised manuscript received April 24,
2006, accepted May 2, 2006. decrease in LV volume and an increased ejection fraction
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908 Christman and Lee JACC Vol. 48, No. 5, 2006
Biomaterials for Treatment of MI September 5, 2006:907 13
with dilated cardiomyopathy; however, they also reported
Abbreviations and Acronyms right ventricular dysfunction and no improvement in cardiac
CSD cardiac support device output. Acorn s pivotal clinical trial encompassing 300
LV left ventricle
patients initially reported that the CSD reduced LV dia-
MI myocardial infarction
stolic volume, improved patient quality of life, and reduced
MMP matrix metalloprotease
the likelihood of additional cardiac procedures (15). How-
PNIPAAM poly(N-isopropylacrylamide)
ever, the significance of the study has been criticized because
of the partial recruitment of patients in an unblinded
fashion, the influence of missing data, and the decrease in
after MI in an ovine model, whereas Sabbah et al. (10)
beneficial effects when patients undergoing concomitant
demonstrated similar effects in a canine chronic heart failure
mitral valve replacement were separated from the analysis.
model, along with reduction of myocyte hypertrophy,
Studies examining epicardial polymeric LV restraints
down-regulation of stretch response proteins, and improved
have had encouraging results; however, a major drawback
sarcoplasmic reticulum calcium cycling. In an effort to more
with this approach is the surgical procedure required for
fully decipher the mechanisms behind the CSD treatment,
Blom et al. (11) reported a normalized myocyte beta- implantation. There are also some conflicting results as to
the real benefit of the CSD in clinical trials, where some
adrenergic response, reduced myocyte length, increased
measures of cardiac function are improved, while others
collagen content, and decreased MMP-9 in a sheep MI
model. Clinical studies have also demonstrated the effec- remain unchanged or deteriorate. Therefore, the results
should be taken with some caution, and there exists a need
tiveness of an LV restraint in humans. Konertz et al. (12)
for more long-term results and a more thorough analysis of
reported an improved ejection fraction and reduced LV
the exact mechanism behind LV restraint.
volume in 27 patients suffering from heart failure 3 and 6
months after receiving a CSD. Franco-Cereceda et al. (13)
also reported increased LV function and decreased LV
IN VITRO ENGINEERED MYOCARDIAL TISSUE
volume in a trial with 8 patients with dilated cardiomyop-
athy. The length of the study was between 12 and 24 Tissue engineering approaches are designed to repair lost or
months. Olsson et al. (14) demonstrated continued, gradual damaged tissue through the use of cellular transplantation
improvement in LV volume and function in 12 patients and biomaterial scaffolds. Numerous studies have examined
Figure 1. Strategies for treatment of myocardial infarction using biomaterials. To date, 3 different biomaterial approaches are being examined for treatment
of myocardial infarction. Polymer meshes can be sutured around the heart for use as a left ventricular (LV) restraint (a) to preserve LV geometry. In vitro
engineered tissue involves culturing cells on a biomaterial scaffold in vitro and then implanting the tissue onto the epicardial surface (b). In situ engineered
tissue can be achieved by injecting a biomaterial alone (d), or using an injectable scaffold as a delivery vehicle for cells (c) or therapeutic agents such as genes
or proteins (e).
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JACC Vol. 48, No. 5, 2006 Christman and Lee 909
September 5, 2006:907 13 Biomaterials for Treatment of MI
Table 1. Biomaterials for Treatment of Myocardial Infarction
Material Transplantation Reference
Left ventricular restraint
Polypropylene Alone 3 6
Polyester Alone 7 14
In vitro engineered tissue
Gelatin Alone or with fetal cardiomyocytes 27
Alginate With fetal cardiomyocytes 28
Poly(glycolide)/poly(lactide) With dermal fibroblasts 29
Collagen type I and matrigel With neonatal cardiomyocytes 30,31
PTFE, PLA mesh, collagen type I, and matrigel Alone or with bone marrow-derived mesenchymal progenitor cells 32
Collagen type I Alone or with embryonic stem cells 33
PNIPAAM (cell culture dish) Cell sheet of neonatal cardiomyocytes or adipose-derived mesenchymal stem cells 36,37
In situ engineered tissue
Fibrin Alone, with skeletal myoblasts, bone marrow mononuclear cells, 45 50,59
or pleiotrophin plasmid
Collagen Alone or with bone marrow cells 48,51,52
Alginate Alone 53
Matrigel Alone or with embryonic stem cells 48,54,55
Collagen type I and matrigel Alone or with neonatal cardiomyocytes 56
Self-assembling peptides Alone, with neonatal cardiomyocytes, or with platelet-derived growth factor BB 57,60
Gelatin With basic fibroblast growth factor 58
PLA poly(L-lactic) acid; PNIPAAM poly(N-isopropylacrylamide); PTFE poly(tetrafluoroethylene).
different scaffolds as well as various culture conditions for increase above 100 m (30), as seen with many in vitro
creating in vitro engineered myocardial tissue (15 25). engineered tissues. Yet, in a more recent study, this group
Those that have been examined in vivo are discussed in this reported 450- m-thick, newly formed myocardium using
review. Li et al. (26) first demonstrated the transplantation this approach, which was shown to improve systolic and
of cells in a biomaterial scaffold for the treatment of diastolic function in rats. Five circular grafts were stacked
myocardial scar tissue. They reported the survival of fetal crosswise to obtain grafts of 1 to 4 mm in thickness that
cardiomyocytes that were seeded onto a biodegradable were subsequently transplanted onto the epicardial surface
gelatin mesh in vitro and implanted onto the myocardial of the infarct (31). Although it was not reported, necrosis
surface in a cryoinjury model; however, the cell seeded grafts within the grafts likely occurred because of the significant
did not improve cardiac function. Leor et al. (27) reported decrease in thickness after transplantation. Grafts were
both survival and preservation of cardiac function with fetal cultured with increased ambient oxygen and insulin, which
cardiomyocytes seeded onto an alginate scaffold, which was may have allowed for the formation of in vitro tissue thicker
subsequently implanted in a rat MI model. The grafts were than the typical 100 m.
found to be vascularized and the scaffold was completely Krupnick et al. (32) also combined cells with a collagen
degraded after 2 months; however, only a small portion of and matrigel mixture. Bone marrow-derived mesenchymal
the graft consisted of myofibers. Transplantation of the progenitor cells were first suspended in the gel, then seeded
scaffold alone was not examined, and thus it is unknown onto a porous poly(L-lactic acid) non-woven mesh, and
whether improvement of cardiac function was a result of finally reinforced with a layer of poly(tetrafluoroethylene).
implantation of the biomaterial or cell transplantation. Instead of implanting the engineered tissue on the epicardial
Kellar et al. (28) also employed a pre-formed scaffold by surface, they sutured it into the infarct wall after a ventric-
using the commercially available Dermagraft, which con- ulotomy. Aneurysmal dilation did not occur with this
tains human dermal fibroblasts cultured on a knitted poly multi-material scaffold. Kofidis et al. (33) mixed embryonic
(glycolide)/poly(lactide) mesh. Transplantation of the Der- stem cells with collagen type I to form an in vitro tissue
magraft onto the LV resulted in significantly higher ejection construct, which was subsequently implanted into the in-
fractions compared to infarcted mice that received no farct wall by surgically creating an intramural pouch in a rat
treatment. heterotopic heart transplant model. Transplanted cells
Rather than seed cells onto a pre-formed scaffold, Zim- formed viable grafts that prevented infarct wall thinning and
mermann et al. (29) combined neonatal cardiomyocytes improved fractional shortening compared to animals that
with liquid collagen type I, matrigel, and cell culture received either the scaffold without cells or no treatment.
medium and then pipetted the mixture into molds to form Yamada et al. (34) and Okano et al. (35) have
the desired shape. Upon transplantation onto the epicardial developed a unique approach for utilizing a biomaterial
surface of uninjured hearts, the engineered tissue was for the creation of patches of cardiac tissue in vitro. They
contractile in vivo up to 8 weeks and was observed to be utilized a temperature-responsive polymer, poly(N-
both vascularized and innervated. In this first study, the isopropylacrylamide) (PNIPAAM), which is slightly hy-
single-muscle bundles in the engineered tissue did not drophobic and cell-adhesive at 37°C but becomes hydro-
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910 Christman and Lee JACC Vol. 48, No. 5, 2006
Biomaterials for Treatment of MI September 5, 2006:907 13
philic and cell-resistant at 32°C because of rapid hydration is thus limited by the lack of retention and vascularization.
and swelling. Tissue culture plates were coated with Another problem associated with the current technique is
PNIPAAM and subsequently seeded with neonatal cardio- that the cells are poorly distributed. Cross sections of the
myocytes. Once the cells formed a monolayer, the temper- infarcted region show clusters of the implanted cells be-
ature was dropped and the cell sheet was removed intact. tween scar tissue. Conduction through the infarcted region
Both cell-to-cell junctions and adhesive proteins within the should thus still be a problem, since the cells are in isolated
monolayers are preserved, unlike with enzymatic digestion areas and may lead to a proarrhythmic heterogeneous milieu
(36). Up to 6 sheets (100 m) may be layered upon each (42). Furthermore, the typical injection technique involves
other to create a 3-dimensional pulsatile cardiac tissue injection of cells in completely liquid solutions and does not
construct without resulting in a necrotic core. More recently, give the transplanted cells a temporary matrix to which they
Miyahara et al. (37) transplanted monolayers of adipose can attach. Cellular cardiomyoplasty does not involve the
tissue-derived mesenchymal stem cells using this cell-sheet use of biomaterials and is thus not fully covered in this
technology, which resulted in improved fractional shorten- review. Several excellent reviews exist that cover this topic in
ing and infarct wall thickness. After 4 weeks, the monolay- detail (43,44).
ers had expanded in situ to produce 600- m-thick tissue The emerging field of tissue engineering has begun to
where it was transplanted over the infarct scar. The newly provide promising alternatives to the typical cellular cardio-
formed tissue consisted of neovasculature, undifferentiated myoplasty technique. Although in vitro-engineered myocar-
mesenchymal stem cells, and a few cardiomyocytes. dial tissue has had some promising results, the limitations
As seen with other in vitro tissue engineering approaches, described previously led to investigations of a different tissue
the majority of external myocardial tissue constructs are engineering approach to cardiac repair. This in situ ap-
limited to a thickness of 100 m or approximately 6 proach utilizes an injectable biomaterial to deliver cells
cardiomyocytes. Studies by both Zimmermann et al. (29 directly into the infarct wall to increase cell survival.
31) and Miyahara et al. (37) demonstrated tissue of approx- Injectable biomaterials can also be utilized in acellular
imately one-half a millimeter in thickness in vivo. Although approaches to support the LV wall and prevent the negative
improved culture conditions were attributed to the thicker remodeling after an MI, or for controlled delivery of
tissue in the study by Zimmermann et al. (29 31), Miya- therapeutic genes and proteins to ischemic myocardium. An
hara et al. (37) transplanted a cell monolayer that then injectable treatment is more minimally invasive than im-
expanded to form a larger graft in vivo. The monolayer of planting in vitro-engineered tissue or an epicardial patch,
mesenchymal stem cells produced only a few cardiomyo- and is therefore more clinically appealing.
cytes, but this study does demonstrate the in situ expansion Christman et al. (45) were the first to demonstrate
capabilities of stem cells in the myocardium. Although these improved cell survival when transplanted cells are delivered
studies offer the hope of regenerating sizable constructs in an injectable scaffold compared to the typical cellular
using an in vitro approach, the current thickness of half a cardiomyoplasty technique. The injectable biopolymer fi-
millimeter is unlikely to produce noticeable changes in brin glue was also shown to induce neovascularization
human myocardium, which is significantly larger than the within the ischemic myocardium and reduce infarct expan-
rat myocardium. Therefore, developing an in vitro cardiac sion. More interesting is the observation that injection of
tissue construct for humans using in vitro approaches is fibrin glue with or without skeletal myoblasts preserved LV
currently a major obstacle. geometry and cardiac function in an acute MI model (46).
Ryu et al. (47) further demonstrated the beneficial effects of
an injectable fibrin glue scaffold by injecting bone marrow
IN SITU ENGINEERED MYOCARDIAL TISSUE
mononuclear cells in the matrix. They likewise reported
Cellular cardiomyoplasty may be considered the first exam- enhanced neovascularization in ischemic myocardium,
ple of in situ cardiac tissue engineering. Cellular cardiomy- which was further confirmed by Huang et al. (48). Chek-
oplasty involves the transplantation of viable cells to replace anov et al. (49) also demonstrated improved cardiac function
necrotic cardiomyocytes. Although studies have shown and neovasculature with endothelial cells in a fibrin matrix
some improvement in cardiac performance by using cellular compared to saline controls; however, injection of fibrin
cardiomyoplasty, there are several problems associated with alone or healthy endothelial cells alone was not examined.
this technique. The current transplantation techniques in- Therefore, it is difficult to conclude what caused the
volve the administration of cells in an aqueous solution improvement. Recently, the use of fibrin glue for the
administered intravenously, intracoronary or directly in- treatment of chronic aneurysms resulting from MI has been
jected into the myocardium; however, the techniques are investigated. Christman et al. demonstrated that the injec-
plagued by limited cell retention and transplant survival tion of fibrin glue into the aneurysm resulting from an MI
(38 41). When reported, the number of animals receiving restored geometry of the LV and markedly improved LV
successful grafts is often low. Given that the cells are function (50). Although the improvement of LV function
injected in an ischemic region of the heart, there is also little was not sustained at 5 weeks after the injection, arrest of LV
to no vasculature to supply the implanted cells. Cell survival dilation and deterioration of LV function occurred.
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JACC Vol. 48, No. 5, 2006 Christman and Lee 911
September 5, 2006:907 13 Biomaterials for Treatment of MI
Other bio-derived materials have also been used for in of the infarct, thereby preventing remodeling and deterio-
situ cardiac tissue engineering. Thompson et al. (51) dem- ration of cardiac function in a similar fashion to LV
onstrated successful injection of bone marrow cells in restraints. On the other hand, a polymer that is too stiff may
collagen into the myocardium via catheter; however, the induce diastolic dysfunction; therefore, the mechanical
injection was done in uninjured hearts, and comparison to properties of the scaffold must be carefully examined.
cell injection in a liquid solution was not performed. Dai While the typical tissue engineering approach involves a
et al. (52) also injected collagen into infarcted myocardium as biomaterial scaffold with cells, such biomaterials may also be
an acellular treatment. They reported improved LV geom- employed as delivery vehicles for therapeutic genes or
etry and cardiac function without increased vascularization proteins in order to stimulate tissue regeneration. Only a
compared to saline controls. In contrast, Huang et al. (48) few studies to date have examined this in the myocardium.
showed an increase in capillary density following injection Iwakura et al. (58) delivered basic fibroblast growth factor
of collagen. Infiltration of myofibroblasts was also reported. via injectable gelatin microspheres and reported increased
Recently, Leor et al. (53) have suggested that intramyocar- angiogenesis as well as improved cardiac function. Christ-
dial injection of alginate induces neovascularization and man et al. (59) also increased neovascularization in ischemic
improved LV function. myocardium by delivering a plasmid encoding the angio-
Kofidis et al. (54) examined an in situ approach using genic growth factor pleiotrophin in fibrin glue. Finally,
matrigel to deliver mouse embryonic stem cells. An LV Hsieh et al. (60) employed self-assembling peptides as a
pouch was formed, similarly to their study using an in vitro delivery vehicle for platelet-derived growth factor-BB. They
approach, and the gel was injected into the area. They reported sustained delivery for 14 days in infarcted myocar-
demonstrated improved LV function in those animals that dium, which decreased cardiomyocyte death and preserved
received the cell-matrigel mixture compared to those that cardiac function compared to either the peptides or the
received either the biomaterial alone or cells in cell culture growth factor alone. They also demonstrated a reduction in
medium. A further study used this approach to directly infarct size. By injecting the therapeutic agent in a bioma-
inject the cells into infarcted murine myocardium (55). terial, a more prolonged delivery profile can be achieved. A
Moreover, Huang et al. (48) demonstrated increased vascu- scaffold can also act as a gene-activated matrix to increase
lature in infarcted myocardium after injection of matrigel. the transfection efficiency of plasmid DNA (61).
Zhang et al. (56) used a mixture of matrigel, collagen, and
cell culture medium to deliver cardiomyocytes, similar to the
FUTURE DIRECTIONS AND CONCLUSIONS
system used by Zimmermann et al. (29 31) in vitro, and
reported preserved LV geometry and cardiac function. Many cell types and tissue engineering approaches have
Davis et al. (57) developed a novel injectable scaffold for improved cardiac function in animal models; however, the
the myocardium using self-assembling peptides, which form exact mechanisms of each approach are currently unknown.
nanofibers upon injection, creating a microenvironment that There are still many questions and issues to be addressed
is suitable for cell and vessel ingrowth. After injection of the before this technology can be safely applied to patients. For
peptides alone into the infarct, progenitor cells expressing instance, finding the best cell source for cardiac repair
endothelial cell markers and vascular smooth-muscle cells continues to remain a major obstacle because of the diffi-
were recruited into the nanofibers. Neonatal cardiomyocytes culty in isolating and expanding autologous sources, the
were also injected with the nanofibers and were found to ethical issues surrounding certain cell types, and the inability
enhance recruitment of endogenous cells. In contrast, little of one cell source to fully replenish all necessary cell types.
recruitment was seen in infarcted myocardium injected with Furthermore, there is little data examining long-term re-
matrigel. sults. Current studies often last 1 to 2 months, and thus may
Taken together, these results suggest that matrigel may not be indicative of long-term outcomes.
be beneficial for delivering cells, but is not ideal for use alone The use of biomaterials for in situ cardiac tissue engineering
or as a scaffold that promotes in situ regeneration. Self- is being appreciated as either a stand-alone acellular solution
assembling peptides appear to have great promise in pro- for cardiac repair or a hybrid therapy used in combination with
moting regeneration, but a suitable cell source for myocar- cells or therapeutic agents. Future studies are needed to
dial regeneration is needed. Alginate, collagen, and fibrin investigate whether biomaterials can be used to help repair
have shown promise for cellular delivery and regeneration, myocardial tissue after an acute ischemic insult and regenerate
but their long-term effects have not been examined. myocardial tissue in a chronic scar. Biomaterials could be used
Whether their benefits will persist months and years after in situ to increase the wall thickness, restore the geometry, and
the scaffold has degraded is unknown. Collagen and alginate provide structural support of an injured LV. The body would
are also known to be mechanically unstable in vivo; thus, be its own bioreactor and allow for infiltration of cells within
when used as a stand-alone treatment, an injectable polymer the scaffold matrix to regenerate myocardial muscle and blood
that is stiffer and either non-degradable or more slowly vessels. Biomaterials have already been shown to recruit cells
degradable may be more beneficial. Such a scaffold may into injured myocardial tissue (48,57). To allow in situ myo-
prevent heart failure by increasing the mechanical strength cardial tissue engineering to become a viable option for the
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912 Christman and Lee JACC Vol. 48, No. 5, 2006
Biomaterials for Treatment of MI September 5, 2006:907 13
treatment of myocardial injury, engineering of biomaterials to extremely useful for both improving cell adhesion and viability,
specifically influence the microenvironment of the myocardium and controlling the host response.
will be required. Such materials should be designed to enhance Because of the difficulties in finding the appropriate cell
recruitment of progenitor cells for myocardial muscle and source, biomaterial treatments such as external LV restraints
or injectable polymers may be more easily realized in the
myocardial vasculature, and increase durability of improved LV
clinic. With the aid of biomaterial scaffolds and a suitable
function. Moreover, the formation of muscle bundles with
cell source, regenerated myocardium may be achieved. We
functioning conductive tissue is a necessity.
are thus optimistic that future studies will continue to
Another important factor for the future success of bioma-
provide more insights and that the field of biomaterials and
terial treatments in the myocardium is the control over the
myocardial tissue engineering will bring new treatments for
tissue response after implantation or injection. Introduction of
those patients with injured myocardium.
a biomaterial into the body can result in a wide range of effects,
both local and systemic (62). Implantation or injection results
Reprint requests and correspondence: Dr. Randall J. Lee,
in local injury, which can then initiate an inflammatory
Cardiac Electrophysiology, MU East Tower, Box 1354, 500
response and foreign body reaction. Acute inflammation,
Parnassus Avenue, San Francisco, California 94143-1354. E-mail:
which can last from minutes to days, is characterized by the
[e-mail].
presence of edema and the migration of leukocytes into the
tissue. Continued exposure to an inflammatory material can
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Biomaterials for the Treatment of Myocardial Infarction
Karen L. Christman, and Randall J. Lee
J. Am. Coll. Cardiol. 2006;48;907-913; originally published online Aug 15, 2006;
doi:10.1016/j.jacc.2006.06.005
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