J. Biomedical Science and Engineering, 2009, 2, 36-40
Published Online February 2009 in SciRes. http://www.scirp.org/journal/jbise JBiSE
Biodegradable and bioactive porous polyurethanes
scaffolds for bone tissue engineering
Mei-Na Huang1, Yuan-Liang Wang1*, Yan-Feng Luo1
National 985 Research Center of Bioinspired Material Science and Engineering, Bioengineering College,Chongqing University, Chongqing 400030, People’s
Republic of China, Correspondence to Yuan-Liang Wang (wyl@cqu.edu.cn). Tel. /fax: +86-23-65102509.
Received September 22nd, 2008; revised November 12th, 2008; accepted November 19th, 2008
Biodegradable porous polyurethanes scaffold
have themselves opportunities in service, in-
cluding controlled degradation rate, no-toxic
degradation products. However, polyurethanes
are lack of bioactive groups, which limits their
application. This review gives the common
modification methods, surface functionalization
and blending modification. In finally, the review
puts forward to the bulk modification as a new
method to enhance the bioactivity of polyure-
Keywords: Polyurethanes, Bioactivity, Biodeg-
radation, Bone Repair
Currently, tissue engineering involving synthetic materi-
als offers a practical approach for bone repair and regen-
eration. In this approach, a 3-D porous biodegradable
scaffold is beneficial to guide cell attachment, prolifera-
tion and tissue regeneration [1,2]. Therefore, a number of
researchers are interested in developing biodegradable
polymeric scaffolds for bone engineering repair [3,4,5,6].
Polyurethane, which concludes the polyurethane urea
elastomer, is regarded as a kind of bone repair materials
for its nice mechanical property and their special shape
memory function.
Biodegradable polyurethanes, made from degradable
polyester/polyether with hydrophilic group of ether bond,
aliphatic diisocyanate, having the hydrophobic group of
alkly and chain extenders [7,8]. Due to these special
group, polyurethanes have controlled degradation rate, in
general, the degradation time can reach to some months
with changing of the ratio polyester/polyether to diiso-
cyanate [7,9], which fits to the growth rate of osteoblast.
Moreover, the degradation give rise to non-toxic prod-
ucts, which will not produce side effect for body. Besides
polyester/polyether and diisocyanate, chain extender is
also a key factor. In order to regulate the pH of degrada-
tion products, and avoid the acid auto-catalytic effect in
the degradation process, and then further controlling the
easily control of degradation rate, some researches
choose diamines [10]. Guan et al [4] synthesized (poly
(etherurethane urea), PEUU) with PCL and 1, 4-diiso-
cyanatobutane (BDI) and putrescine. And then, PEUU
was made into highly porous, biodegradable polyure-
thane scaffold for tissue engineering. In this study, BDI
was used, since it could release putrescine, a polyamine
that is essential for cell growth and proliferation. Zhang
et al [11] synthesized polyurethane by reacting of highly
pure lysine diisocyanate with glucose, which resulted in
major degradation products lysine and glucose (LDI-
glucose), and then completely degradate and enter into
human circulation system.
The degradation mechanisms of polymers are impor-
tant and need to be investigated further. Non-toxic deg-
radation products are necessary and, moreover, me-
chanical properties are also influenced by degradation
mechanisms. LDI-glucose [11] polymer, for example, is
degraded by hydrolysis of urethane bonds to liberate
lysine, glucose, ethanol, and CO2. Ethanol could inhibit
cell-cell adhesion, but a study reported that concentra-
tions less than 30mM are harmless to the cell. Moreover,
in contrast to PLA and PLGA degradation mechanisms,
the study showed that the degradation of polyurethane
with diamine no significant increase in pH of the solu-
tion. PEUU degradation products were also shown to be
non-toxic to endothelial cells. The polymer showed a
linear degradation with no signs of autocatalytic effects
when compared to PLA or PLGA degradation behaviour.
In addition, regulating ratio of polyester/polyether to
diisocyanate can change the molecular weight of poly-
urethane, and then control their degradation rate. The
two regulation methods make it be balance with growth
of cell/tissue and realize the real tissue engineering re-
However, polyurethanes as a potential, biodegradable
materials are lack of bioactive groups, which limits their
applications. Therefore, how to ensure biodegradation
and bioactive of polyurethane are two key factors for it’s
application in bone repair [12,13]. A further requirement
for scaffold, particularly used for bone engineering, is
controllable interconnected porosity for cells to grow
into the desired physical form and to compete vasculari-
zation of the ingrown tissue [12]. Other highly desirable
SciRes Copyright © 2009
M. N. Huang et al. / J. Biomedical Science and Engineering 2 (2009) 36-40 37
SciRes Copyright © 2009 JBiSE
features concerning the scaffold processing are near-net
-sHAe fabrication and scalability for cost-effective in-
dustrial production [12,14].
In the paper, we only discuss how to enhance the bio-
activity of porous polyurethane scaffold. In general, bio-
active functionalization methods of polyurethanes can be
concluded to three major design strategies [15,16,17,
18,19]. One approach is blending the polyurethanes with
tricalcium phosphate/ hydroxyapatite or other inorganic
ceramic [16,17,18,19]. Various bioactive factors further
enhance the cellular compatibility. The inorganic ce-
ramic have another advantage, the function of bone in-
duction and the conduction [16,17,18,19]. The other ap-
proach involves endowing the biomaterials with bioac-
tivity by incorporating soluble bioactive molecules, such
as growth factors and plasmid DNA, into biomaterial
carriers so that the bioactive molecules can be released
from the materials and trigger or modulate new tissue
formation [20,21,22]. The last one is incorporation of
cell-binding peptides into biomaterials via chemical or
physical modification. The cell-binding peptides include
a native long chain of extracellular matrix (ECM) pro-
teins as well as short peptide sequences derived from
intact ECM proteins that can incur specific interactions
with cell receptors [15,23,24,25] This paper reviews
above methods and focuses on their opportunities as a
kind of bone repair materials, and puts forward a new
method to improve the bioactivity of biodegradable
Tissue engineering applies methods from materials en-
gineering and life sciences to artificial construction new
tissue. Two common approaches are transplanting the
biomaterials with cell [26] or the biomaterials with some
bioactive factor/bioactive substance for the cell homing
to realize restoration. Facing the complex biological and
sensitive human body, requirements of biomaterials are
extremely challenging. The First and most, compared to
other bioactive materials, polyurethanes are lack of bio-
active factors and cytocompatibility [27], which can be
well solved by introduction of bioactive substances, in-
cluding the inorganic phosphate, growth factors and ex-
tracellular matrix.
2.1. Introduction of Inorganic Phosphate
Into Polyurethanes
Hydroxyapatite, glasses, glass-ceramics or calcium
phosphates having similar components with natural bone
[14,20], are important categories of bioactive materials.
Coating and blending are the most common methods to
modify polymer with inorganic phosphate. Biomimetic
method is a chemical modification with inorganic phos-
phate [28,29,30].
Hydroxyapatite (HA), the most important inorganic
phosphate, has been extensively investigated over the
past few decades as a biomedical material. It can be de-
signed as a bioactive material, besides it is similar com-
position with natural bone, osteoconducive, osteoinduc-
tivity, biodegra-dability, high mechanical strength and
their medical products such as screws, plates and rods
have been commercial forms a strong bond to natural
bone in vivo [31,32,33]. Moreover, the introduction of
HA can regulate the pH of biomaterials. Above proper-
ties of hydroxyapatite and other inorganic phosphate can
induct the growth of bone and prevent the inflammatory
reaction [31,32,33,34].
Rezwan, K. et al [13] reviewed the function of bioac-
tive glasses, glass-ceramics and the calcium phosphates
or HA in the enhancement of the bioactivity of polyure-
thanes. It has been found that reactions on bioactive
glass surfaces can release critical concentrations of solu-
ble Si, Ca, P and Na ions, depending on the processing
route and particle size. The released ions induce intra-
cellular and extracellular responses. One key reason that
makes bioactive glassed-correlation material is the pos-
sibility of controlling a range of chemical properties and
thus the rate of bioresorption. Park, Y.S. et al [35] inves-
tigated the fabrication method of a three-dimensional
reticulated scaffold with interconnected pores of several
hundred micrometers using calcium phosphate glass in
the system of CaO-CaF2-P2O5-MgO-ZnO and a polyure-
thane sponge as a template. It is thought that this kind of
biodegradable glass scaffold combined with osteogenic
cells has potential to be studied further as a tissue engi-
neered bone substitute. The structure and chemistry of
glasses, in particular sol-gel derived glasses, can be tai-
lored at a molecular level by varying either composition,
or thermal or environmental processing history.
Above inorganic phosphate is important bioactive
modification material, however, current technology is
difficult to solve the compatibility between inorganic
phosphate and polyurethanes. It is difficult to make a
uniform matrix, particularly, the current coating/blending
methodswhich result in that it is difficult to form a
uniform matrix, particularly, the content of inorganic
ceramic is high [36,37]. Some researches found that
some of HA/PLA composites lost their strengths rapidly
in physiological environment and failures occur mainly
at the interface of HA and the polymer matrix. Two main
reasons may take responsibility for these interfacial fail-
ures: one is lack of effective adhesion between ceramic
phase and polymer matrix; the other is self-catalytic
degradation of hydroxyl groups on HA surfaces to poly-
mer main chains. The structure of polyurethanes/HA is
similar to HA/PLA, which may result in the same inter-
face separation. For solving the problem, Xian, Y.M
adopted chemical reaction to produce HA crystal on the
polymer surface, the chemical reaction to make inorganic
phosphate in the surface polymer can solve the interface
separation, however, another problem appeared [30]. The
reaction of making HA/polymers crystal is similar to the
biomimetic calcification, which lasted for more than one
week, and then make negative effect on the polymers.
Moreover, the products can not ensure the crystal struc-
38 M. N. Huang et al. / J. Biomedical Science and Engineering 2 (2009) 36-40
SciRes Copyright © 2009 JBiSE
Introducing inorganic phosphate can not wholly solve
the bioactivity problem. Some researchers use bioactive
factor, which can react with polymers to enhance their
bioactivity [38,39,40], such as RGD, moreover, the bio-
active factors is important for cell homing.
2.2. Surface Modification of Porous Polyure-
thanes Scaffold with Bioactive Factors
2.2.1. Arg-Gly-Asp(RGD) Modified Biomimetic
In an effort to improve the adhesion and retention of
cells to polymer scaffolds, researches typically coated
with various extracellular matrix proteins [40,41,42].
These studies highlight that extracellular proteins played
an important role in attachment and spreading of cells to
surface, where specific domains on cell membrane bind
directly with extracellular matrix moleculaes via in-
tegrins [43,44]. A number of specific cell-recognition
sequences have been identified, the most extensively
studied sequence being the arginine-glycine-aspartic acid
(RGD) motif present in matrix molecules such as vi-
tronectin, fibronectin, laminin and collagen, fibrillin
RGD peptide is one of the major bioactive factor to
design biomimetic polyurethanes and has been widely
researched in recent years [38,39,40]. In order to provide
a stable linking, RGD peptides should be covalently at-
tached to polymer via functional groups like hydroxyl-,
amino-, or carboxyl-groups. Some polyurethanes are
amino-terminated [4,38], which can react with the car-
boxyl-groups of RGD, with 1,3-Dicyclohexylcar-
bodiimide (DCC) as catalyst. Other polyurethanes are
hydroxyl-terminated, the hydroxyl-also can react with
the carboxyl-group of RGD [48].
Moreover, in order to enhance the surface functionali-
zation, polymeric materials, such as polyurethane must
be functionalized before bioactive peptides or proteins
are immobilized on their surfaces [44]. In general, the
functionalization can be realized by a variety of means,
either by introduced the multi-functional groups mono-
mer or polymer[39], or by subsequent surface modifica-
tion by plasma treatment [45] ozone oxidation [46] sur-
face graft polymerization [40] or site-specific reactions
[47]. Here, we put emphasis on two examples to demon-
strate the successful application of linking group in sur-
face modification. One example [39], the difunctional
spacer molecule-diisocyanate is introduced as the linking
group of polyurethane film and RGD, realizing the sur-
face functionalization of polyurethane. Another example,
Jozwiak, A.B [40] used two steps to enhance the intro-
duction rate. First, the multi-amino group-polyethyle-
neimine (PEI) is introduced, a medium sized molecular
weight branched form of PEI was used here in order to
provide a large number of reactive primary amine groups
and enhance its entrapment within the polyurethane sur-
face. Second, introducing the dextran, which is func-
tional spacer molecule and can link the RGD easily.
2.2.2. Growth Factors Modified Biomimetic Poly-
Chemotaxis, proliferation, differentiation and matrix
synthesis are essential in natural tissue/organ develop-
ment and wound healing [45]. Owing to the rapid ad-
vances in recombinant technology and the availability of
large scale manufacturing of cytokines and growth fac-
tors, many recent tissue engineering strategies have
turned to specific growth factors to stimulate cellular
activity in vitro and to improve functional neotissue
formation in vivo [47,48]. Characteristic of these bioac-
tive factors is that they can effective release at specific
site and realize the function of improving cell prolifera-
tion and recruitment [46,49]. Incorporation of angiogenic
growth factors such as basic fibroblast growth factor
(bFGF) and vascular endothelial growth factor (VEGF),
among others, into scaffolds for controlled release has
been shown to promote lacal angiogenesis [50]. Plate-
let-derived growth factor (PDGF) has been demonstrated
to stimulate proliferation and recruitment of both perio-
dontal ligament and bone cells in vitro. In vivo study
also showed that PDGF-BB enhances the ability of heal-
ing [46].
There are many methods to incorporate growth factors
into synthetic scaffolds, such as absorbing growth factor
to scaffold, and blending growth factor containing mi-
crospheres into the scaffold [46], or directly mixing
growth factor containing protein powder into the scaffold
during processing [50]. However, absorbing growth fac-
tors onto the scaffold has the drawback of low loading
efficiency and rapid releasing, which may be associated
with in bioactivity due to harsh solvents such as hexane
[46] or methylene chloride [51]. Incorporating growth
factor directly into the scaffold can potentially avoid
these shortcomings.
Whether or not has bioactivity of the released bioac-
tive factors is an essential problem. Bioactivity of the
factors can be assessed in two methods [47,50,52]. First,
bioactivity of the released factor can be determined
through the direct method-human gingival fibroblase
DNA synthesis as measured by specific composition [46].
Second, the bioactivity is assessed in terms of its ability
to stimulate the growth of cells [50,52].
3.1. Possibility and Challenge of Bulk Modi-
fication for Polyurethanes
Besides above methods, how can we improve bioactivity
of polymers? Now, a great wealth of knowledge about
the biology of integrin mediated cell adhesion has
proved that the modification of polyurethanes with RGD
peptides or other bioactive factors are useful tool to de-
sign bioactive porous scaffolds that can provide biologi-
cal cues elicit specific cellular responses and direct new
tissue formation. However, the surface modification has
some limitations. Since surface modification has been
performed on well-defined model surfaces and the
M. N. Huang et al. / J. Biomedical Science and Engineering 2 (2009) 36-40 39
SciRes Copyright © 2009 JBiSE
evaluation of cell behavior on material has been con-
ducted under serum free media, the results may not
properly indicate complicated events associated with in
vivo environments. Even though some model surfaces
may be useful to provide fundamental knowledge to un-
derstand cell behavior through specific binding, they
may not be directly used as tissue engineering scaffolds.
If we use bulk designing of polyurethanes, incorpo-
rated RGD or collagen may result in recognition sites is
present not only on the surfaces but also in the bulk of
the materials. Niu, X.F. et al [53] review the bulk modi-
fication, which describe the bulk modification of bioma-
terials is beneficial to tissue engineering applications
where injectable biomimetic materialsare required to
match the complex HA of native tissue at defect sites.
Cook et al [54] and Barrera et al [55] conducted a lot of
investigations in understanding the effects of bulk modi-
fication via RGD peptides. They synthesized RGD bulk
modified poly (lactic acid-co-lysine) and successfully
blended it with PLA to fabricate a thin film. When this
film was exposed to endothelial cell suspended media for
4 h, the specific function of RGD was maintained to fa-
cilitate cell spreading.
Polyurethanes are the biomaterials with hydroxyl-
terminated and amine-terminated. The RGD or other
peptide can react with the terminal group of polyure-
thanes, which may result in bioactive polyurethanes. My
laboratory chose the bulk modification to introduce the
bioactive factor, such as RGD/MGF, and then emul-
sion/freeze drying mean was adopted to make porous
polyurethane scaffold with bioactivity polyurethane.
3.2. The Possibility of Introduction of Inor-
ganic Phosphate by Chemical Reaction
Inorganic phosphate is important component of natural
bone, however, current technology is difficult to solve
the compatibility between the inorganic phosphate and
How to introduce the inorganic phosphate, and at the
same time avoid above disadvantage is a key problem for
enhancing the stability of polyurethane/inorganic phos-
phate composition. In order to overcome these limita-
tions of composite, covalently attached the inorganic
phosphate to polyurethanes by linking group may be a
feasible method. Linking group should easily react with
the hydroxyl-from inorganic phosphate and the carboxyl-
or amino-group from polyurethanes. Silane derivatives
are used as modification molecular to link hydroxyl
groups (-OH) in HA surface to polymer main chain,
which is carried out via direct reactions of –OR groups
on HA surfaces. At the same time, other functional
groups (-NH2) of silane derivatives may further react
towards the terminal groups carboxylic group or hy-
droxyl group. Moreover, glutaraldehyde [43] may be the
important cross-linking agent. In addition, in order to
ensure the homogeneity of composite, the effective con-
nection of emulsion blending-chemical crosslinking may
be an efficient method [44].
For realizing biodegradation, bioactivity and me-
chanical property of the bone repair materials, the paper
puts forward two methods to make the biodegradable
materials, which are equipped with the uniform structure
and bioactive components.
The authors gratefully acknowledge the financial support from the
“Eleven-Five” National Science and Technology Support Program of
China (2006BA103B04).
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