Available online at SciVerse ScienceDirect

J. Mater. Sci. Technol., 2013, 29(6), 503e513

Biodegradable Materials for Bone Repairs: A Review

Lili Tan, Xiaoming Yu, Peng Wan, Ke Yang*
Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016, China
[Manuscript received February 8, 2013, in revised form February 19, 2013, Available online 21 March 2013]

Prof. Ke Yang is the leader of Specialized Materials and Devices Division of Institute of Metal Research, Chinese Academy
of Sciences. He focuses on R&D of advanced structural steels, novel metallic medical materials, hydrogen storage alloys
and applications. For the novel metallic medical materials research, high nitrogen Ni-free stainless steel, anti-infection
stainless steel, anti-ISR stainless steel, biodegradable magnesium-based metals, antibacterial titanium alloys, are
included, as well as the related metal surface modification techniques, and promoting applications of them in ortho-
paedics, dentistry and coronary stents.

With attractive research and development of biomaterials, more and more opportunities have been brought to the
treatments of human tissue repairs. The implant is usually no need to exist in the body accompanied with the
recovery or regeneration of the tissue lesions, and the long-term effect of exotic substance to human body
should be reduced as lower as possible. For this purpose, biodegradable materials, including polymers,
magnesium alloys and ceramics, have attracted much attention for medical applications due to their
biodegradable characters in body environment. This paper in turn introduces these three different types of
widely studied biodegradable materials as well as their advantages as implants in applications for bone
repairs. Relevant history and research progresses are summarized.

KEY WORDS: Biomaterial; Biodegradable; Polymer; Magnesium; Ceramic; Bone repair

1. Introduction let alone contagious disease and tumorigenesis. Because of their

As an important biomaterial for human hard tissue replace-
ment and repair, bone repair materials are widely applied in bone
surgery, orthopedics and dentistry[1e13]. The number of patients
with bone defects induced by traumas, inflammations and tumors
are enormous, so the requirement for bone replacement is also
huge. As a result, the development of bone repair materials has
attracted much attention. Autograft bones, allograft bones and
artificially synthesized materials are the main bone repair mate-
rials[14e16]. Although the autograft bones are the ideal materials
for bone repair, their resources are limited and the secondary
surgeries increase the pains of patients. Furthermore, the
abnormal morphology and dysfunction probably take place in
the supply zone. As for autograft bones, the immune rejection
reactions are the main restriction to the wide application,
* Corresponding author. Prof., Ph.D.; Tel.: þ86 24 23971628; Fax: þ86
24 23971676; E-mail address: kyang@imr.ac.cn (K. Yang).
1005-0302/$ e see front matter Copyright Ó 2013, The editorial office of
Journal of Materials Science & Technology. Published by Elsevier
Limited. All rights reserved.
http://dx.doi.org/10.1016/j.jmst.2013.03.002
advantage on flexibility and designability, more and more arti-
ficially synthesized bone repair materials come into people’s
sight. As a result, improvements on the existing bone grafts or
the development of brand new bone repair materials have
become a hotspot for research.
According to the degradation performance, bone repair ma-
terials can be classified into two groups: bio-inert and biode-
gradable materials[17,18]. The bio-inert materials have had a long
history in clinical use, which are the most widely adopted
medical materials. Although the inert implants have shown un-
doubted success in application as internal fixations of bones, they
do have some unavoidable problems. For example, as the per-
manent implant materials, the inert implants stay in human body
forever until they are malfunctioned. The secondary surgery
increases not only the cost but also the pain for patients.
Nowadays, biodegradable materials have attracted much atten-
tion because of their unique degradable characters[19e25]. With
degradation of the implants, accompanying with decrease of
mechanical properties of the implanted materials, the loads will
gradually transfer from the implants to human bones and soft
tissues to avoid the stress shield effect. Furthermore, they do not
require removals. The development of these biodegradable
504 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513

implants such as rods, plates, pins, screws, suture anchors and

sutures for fixations is progressed in recent years.
Biodegradable polymers, metals and ceramics are the main
three kinds of widely studied biodegradable biomaterials. In this
article, the history and latest achievements on these three
biodegradable materials are summarized, their bio-
compatibilities, degradation mechanisms and applications as
medical implants are also reviewed. Fig. 1 Structural formula of PLA.

2. Biodegradable Polymers
Among those biodegradable materials, the biodegradable
polymer is one of the important materials. Biodegradable poly-
mers are the primary materials for tissue engineering applications
and bone repair implants. Based on their origin, they can be
classified as natural-based materials and synthetic polymers. The
common polysaccharides (starch, alginate, chitosan, hyaluronic
acid derivatives, etc.) and proteins (collagen, fibrin gels, silk,
etc.) belong to natural-based materials. But their applications are
dramatically restricted due to their high physiological activity,
repellency, unknown degradation rate and low mechanical
properties. As for the synthetic polymers, by careful design and
accurate control, polymers with better properties than natural-
based materials can be prepared to accomplish various
requirements.
What is a polymer? Polymers are those macromolecules
composed of covalently bonded monomers[21]. The repeating
monomers of a polymer can be the same or different, i.e., ho-
mopolymer and copolymer. For copolymer, the number and type
of monomers can be different. Polymer chains can be linear,
branched, or cross-linked with other chains. Meanwhile, the
polymer can also be amorphous or crystalline. Furthermore,
there are even amorphous or crystalline regions in the same
polymer, which affects the strength and absorption of these im-
plants[26]. The properties of polymers are also affected by tem-
perature. Above the glass transition temperature (Tg), the
polymers become flexible. It is important to make biodegradable
polymers with Tg above the body temperature[21].
2.1. Commonly used biodegradable polymers
There are different kinds of synthetic biodegradable polymers,
such as polylactic acid (PLA), polyglycolic acid (PGA), poly-
3-caprolactone (PCL) and poly-b-hydroxybutyrate (PHB)
[27e29]
.
As a family of linear aliphatic polyesters, PGA, PLA and poly
(lactic acid-co-glycolic acid) (PLGA) that is a copolymer are
most frequently used in tissue engineering and bone repair im-
plants[1e6]. They have been demonstrated to be biocompatible
and degraded in vivo into non-toxic components with control-
lable degradation rates, and have been a long history of uses as
degradable surgical sutures[30e33], having gained US Food and
Drug Administration (FDA) approval for clinical use.
2.1.1. PLA. As the most widely used biodegradable polymer,
PLA has been studied for nearly 50 years[20,34e36]. It was first
discovered in 1780 by a Swedish chemist, Scheele. In the 1960s,
for medical application, PLA was first reported to be used as
sutures and rods for the repair of mandibular fractures in
dogs[37,38]. In 1988 a project to develop PLA was launched by
Cargill Inc., USA. The goal of the project was to establish a new
product and value opportunities for starch processed by the
company[39]. Nowadays, PLA is a kind of new polymer that is
made from 100% renewable resources like corns. For the most
widely used PLA in clinic, it is approximately classified into two
groups: L-PLA (crystalline in most) and DL-PLA (amorphous in
most)[20]. L-PLA is highly resistant to hydrolysis, while DL-PLA
is more sensitive to hydrolysis[40]. In fact, PLA is used in form of
the copolymer of these two kind of isomeric monomers. The
structural formula of PLA is shown in Fig. 1.
2.1.2. PGA. PGA is a synthetic polymer of glycolicacid, syn-
thesized by ring opening of the cyclic diesters of glycolic acid.
With high crystallinity, melting point and low solubility, PGA
was the first for use in clinic as the biodegradable suture lines. In
1962, DexonÒ was developed as biodegradable suture lines by a
USA company, Cyanamid Co., which is made of PGA[41].
Because of its hydrophilism, PGA has a high degradation rate.
Usually, its mechanical strength decreases to 50% of the origin
after implantation for 14 days and to 90e95% after 28 days.
Therefore, PLGA, which is the copolymer of PGA and PLA, is
most frequently employed for clinical application. Vicryl and
Polyglactin 910 are the widely used biodegradable fibers which
are made of PLGA. Hydroxyacetic acid is the degradable
product of PGA and it is discharged through kidney, or it is
metabolized by liver with final products of CO2 and H2O. No
toxicity, no aggregation and biodegradation are the main ad-
vantages for PGA used as a biomaterial[42e46]. The structural
formula of PGA is shown in Fig. 2.
2.1.3. PCL. PCL is a biodegradable aliphatic polyester that is
currently being studied for use in medical implants. The struc-
tural formula of PCL is shown in Fig. 3. Because of its hydro-
phobic behavior, it is not easy to control the degradation rate
only by adjusting its molecular weight. Compared with PGA and
PLA, PCL has a much lower degradation rate due to its high
crystallinity. PCL is a hemihedral crystal with about 45% crys-
tallinity. Consequently, PCL can be probably used as the long-
term implant. Owing to its drug permeability, PCL is usually
used as a drug release carrier. Due to its good flexibility and
machinability, PCL can be squeezed out, molding injected,
stringed and spread out to form in various shapes. With good
biocompatibility and biodegradability, PCL can also copoly with
other polymer biomaterials[47,48].
2.1.4. PHB. PHB is also a kind of biodegradable polyester
whatever it is natural or synthesized[49,50]. This polymer is a
highly stereoregular biopolymer produced by many strains of
bacteria as a storage medium. PHB is highly crystalline and
Fig. 2 Structural formula of PGA.
 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
Fig. 3 Structural formula of PCL.
orthorhombic[51]. It has also been proved to be useful as a model
material for the study of physical properties of polymers. For
example, PHB has been found to be an excellent model material
for the study of polymer nucleation because it contains no
catalyst residual and has perfect tacticity, which is a result of the
biological origin[52]. Consequently, PHB has attracted much
attention as a degradable resin to be used for a wide range of
medical applications[28]. However, practical use of PHB for these
applications has been limited by its brittleness and narrow pro-
cessing window. It is known that the growth of cracks within the
large spherulites of PHB is the origin of its brittleness. Much
work on blending it with other polymers to decrease both the
brittleness and the melting point has been reported[53e56].
Furthermore, PHB has also been used to study the miscibility
and crystallization behavior with other polymers[57e60].
2.1.5. PDS. PDS (poly-para-dioxanone) is a kind of biodegrad-
able polyester used in tissue engineering, bone fracture
fixation, and controlled drug delivery due to its excellent
biodegradability, bioabsorbability, biocompatibility, and me-
chanical flexibility[61e64]. The structural formula of PDS is
shown in Fig. 4. PDS possesses outstanding potential for use in
general medical implants in the form of films, molded products,
laminates, foams, non-woven materials, adhesives and
coatings[65,66]. In the 1970s, later than PLA and PGA, PDS was
first developed. However, because of its unique physical and
biological properties, PDS is universally acknowledged as the
first choice for the fracture internal fixation material. PDS frac-
ture internal fixation material is completely bio-absorbable in
bone tissues[67, 68]. With the degradation of PDS, new bone
tissue can deposite on the fixation implants. PDS can be
completely vanished within 180e200 days via control of its
molecular weight, crystallinity and melting temperature.
2.2. Physicochemical and mechanical properties of
biodegradable polymers
Table 1 shows the properties of some biodegradable poly-
mers[69]. The thermal, mechanical, and biodegradation charac-
teristics of PLA and other polymers depend on the choice and
distribution of stereoisomers within the polymer chains, such as
poly (L-lactide) (PLLA) and poly (D-lactide) (PDLA). The degree
of crystallinity depends on many factors, such as molecular
weight, thermal and processing histories, and temperature and
time of annealing treatments. In particular, PLLA is always
preferred whenever higher mechanical strength and longer
degradation time is required[70].
Fig. 4 Structural formula of PDS.
505
2.3. Degradation mechanism of biodegradable polymers
These polymers degrade through hydrolysis of the ester
bonds[48], which could result in a dramatic change of their
chemical structure. In addition, adhered by microorganisms on
surface of the polymer, the macromolecules will become rela-
tively small molecular debris by the effect of enzyme secreting
by microorganisms, and then be eventually eliminated from the
body in the forms of carbon dioxide and water. The degradation
rate can be affected by the chemical composition, crystallinity,
molecular weight and distribution, so it can be tailored to satisfy
a specific requirement from several weeks to several years by
altering the mentioned parameters. The biodegradation of poly-
mers can be classified as: (1) Physical biodegradation: when
microorganism attacks the polymer, it will be hydrolyze and
ionize or protonize to become the oligomer debris. The molec-
ular structure of oligomer is all the same with the polymer. (2)
Chemical biodegradation: under the direct effect of microor-
ganism or enzyme, the polymer will be degraded into micro
molecules, eventually, become carbon dioxide and water. How-
ever, because of the high selectivity for the micro-biological
degradation, degradation mechanisms for many polymers are
still not completely clear.
2.4. Application of biodegradable polymers in bone repair
For a long time, metals have been always used as the bone
repair materials. Although they possess high mechanical
strength, which is appropriate for internal fixation of bones, the
relevant shielding effect inducing osteoporosis and the corrosion
resulting in secondary surgery are the main restrictions for their
clinical application. Polymers, such as PGA, PLA and PLGA
with relatively high elastic modulus, tensile strength and low
elongation at break, are also suitable for bone repairs[19]. The
bone screw and splint made of PLA or PLGA are not easy to be
corroded[71]. However, they will biodegrade with increase of the
implantation time and their strength are correspondingly
decreased. Then, the stress transfer to bone and the osteoporosis
are eventually avoided as well as the secondary surgery. With the
development of syntheses technology, the strength of polymer is
enough to be used as the bone lamella material such as thigh-
bone. For the polymers with relatively low strength, they can be
employed as anklebone, patella, phalanx and various fixed
screws, etc. However, relatively low mechanical strength, X-ray
transparency and the non-specificity foreign body reaction
caused by individual difference are the main disadvantages for
polymers[72]. At present, the most widely used bone fixation
polymers are PLGA known as Lactosorb Craniomaxillofacial
Fixation System (Biomet). Natureworks LLC Natureworks
PLAÒ and IngeoTM, and Kanebo LactronÒ are the main PLA
products.
3. Biodegradable Magnesium Based Metals
Magnesium (Mg) based metals, including pure magnesium
and its alloys, are attracting much attentions for medical appli-
cations owing to their easy corrosions in body environment,
which can be taken as characteristics of biodegradation if the
corrosion products are bio-safely absorbed or excreted. In the
late 19th century, magnesium was tried to be used as the implant
material, shortly after the discovery of elemental magnesium by
Sir Humphrey Davy in 1808. Some clinic trials were made on
magnesium implants, including ligatures, connectors for vessel
506 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513

Table 1 Properties of biodegradable polymers[69]

Polymer Thermal & mechanical properties Degradation properties Processing and applications

Melting Glass transition Tensile Time Solvent Applications

temperature ( C) temperature ( C) modulus (GPa) (months)

PLA 173e178 60e65 1.5e2.7 12e18 Choloroform Fracture fixation,

Dioxane Interference screws,
Dichlorometane Suture anchors,
Etylacetate Meniscus repair
Acetone
Tetrahydrofuran
Hexafluoroisopropanol
PGA 225e230 35e40 5e7 3e4 Hexafluoroisopropanol Suture anchors,
Acetone Meniscus repair,
Dicholoremthane Medical devices,
Choloroform Drug delivery
PCL 58e63 60 0.4e0.6 ＞24 Choloroform Suture coating, dental
Hexafluoroisopropanol Orthopedic implants
Dichlorometane
Toluene
PLGA (50/50) Amorphous 50e55 1.4e2.8 3e6 Choloroform Suture, drug delivery
Dichlorometane
Etylacetate
Acetone
Tetrahydrofuran
Hexafluoroisopropanol
Choloroform
Dichlorometane
PLGA (85/15) Amorphous 50e55 1.4e2.8 3e6 Etylacetate Interference screws,
Acetone Suture anchors, ACL
Tetrahydrofuran Reconstruction
Hexafluoroisopropanol
PLGA (90/10) Amorphous 50e55 e <3 Choloroform Artificial skin,
Dichlorometane Wound healing, suture
Etylacetate
Acetone
Tetrahydrofuran

anastomosis, wires for aneurysm treatment, as well as osteo-
synthetic applications. Magnesium based metals with biode-
gradable behaviors possess superior strength to weight ratio
compared to those of other biodegradable materials. However, a
critical problem to be settled is how to well control the degra-
dation rates of magnesium based metals.
Biodegradable magnesium based metals are potential to be
used as a new class of biodegradable medical implant materials
since they possess many advantages over the current applied and
developed biomaterials as the follows.
of magnesium based metals (about 45 GPa) is more close
to that of natural bones. Hence, the stress shielding effect
induced by serious mismatch in modulus between natural
bones and metal implants is expected to be mitigated.
4) Close density with bones: Densities of magnesium based
metals (1.7e2.0 g/cm3) are close to those of natural bones
(1.8e2.1 g/cm3), compared with titanium alloys (4.42 g/cm3
for Ti-6Al-4V), stainless steels (about 7.8 g/cm3),
biodegradable polymers (about 1 g/cm3 for PLLA) and
hydroxyapatite (3.156 g/cm3).

1) Good biological behaviors: Magnesium is an element
essential to the human body. Mg2þ is the fourth most
abundant cation in the human body and is largely stored in
bone tissues. The direct corrosion product of magnesium,
Mg2þ, is easily absorbed or consumed by the human body,
and can be excreted in urines[73].
2) Good mechanical properties: Magnesium based metals
have obvious advantage over the currently developed
biodegradable materials such as polymers, ceramics and
bioactive glasses in load bearing applications that require
higher strengths.
3) Close modulus with bones: Compared with titanium alloys
(about 110 GPa), stainless steels (about 200 GPa) and
cobalt based alloys (about 230 GPa), the elastic modulus
3.1. Current studies on biodegradable magnesium alloys
3.1.1. Commercial magnesium alloys. Commercialized mag-
nesium alloys developed for the engineering application pur-
poses have relatively better combinations of mechanical
properties and corrosion resistances. Therefore in the beginning,
some commercial magnesium alloys were directly selected as the
biodegradable magnesium alloys for investigations. WE43 alloy, a
rare earth elements strengthened magnesium alloy, was earlier to
be developed as a biodegradable magnesium alloy for the bio-
absorbable coronary stents[74]. AZ31B alloy, an MgeAleZn
alloy, was also manufactured into bio-absorbable coronary stents
with drug eluting coating (SEBMAS)[75]. Witte et al. reported that
the implant made of AZ91 alloy, another MgeAleZn alloy,
 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
showed no significant harm to its neighboring tissues and also
exhibited good biocompatibility[24]. No skin sensitizing potentials
were detected for the currently studied commercial magnesium
alloys including AZ31, AZ91, WE43 and LAE442[76]. In addi-
tion, pure magnesium has also been investigated as a biodegrad-
able implant material since it has single elemental composition,
high purity and uniform degradation behavior [77, 78].
Originally the commercial magnesium alloys were not
designed for medical applications, thus there may exist some
potential problems. Aluminum (Al) ions released from AZ91
alloy could easily combine the inorganic phosphates, leading to a
lack of phosphate in the human body, and an increased con-
centration of Al ions in brains seems to be associated with the
Alzheimer’s disease. Severe hepatotoxicity has been detected
after the administration of rare earth elements such as cerium,
praseodymium and yttrium[79]. Therefore in the past few years,
some new magnesium alloys oriented for medical applications
have been developed, mainly including the alloy systems of
MgeCa, MgeZn, MgeRE, MgeMn, etc.
3.1.2. MgeCa alloys. Ca has a low density (1.55 g/cm3), which
endues the MgeCa alloy system with an advantage of similar
density to bone[80]. Magnesium is necessary for the incorporation
of Ca into bones, which is expected to be beneficial to the bone
healing with co-releasing both Mg and Ca ions[80]. For this pur-
pose MgeCa alloys have been studied by several research groups
in the world as a class of novel biodegradable magnesium alloys.
Binary MgexCa (x ¼ 1e3 wt%) alloys with various Ca contents
under different processing conditions were studied[78], which was
generally composed of two phases, alpha-Mg and Mg2Ca. An
increase of Mg2Ca phase in microstructure led to a higher corro-
sion rate for the alloy, whereas hot rolling and hot extrusion could
reduce the corrosion rate. Mge1Ca alloy did not induce cyto-
toxicity to cells, and high activities of osteoblasts and osteocytes
were observed around the Mge1Ca alloy pins implanted in rabbit
femoral shafts[80], showing good biocompatibility and bioactivity.
3.1.3. MgeZn alloys. Zinc (Zn) is an essential element in the
human body and it has also an even more strengthening effect in
magnesium alloys[81]. Zn could elevate both the corrosion
potential and the Faraday charge transfer resistance of magne-
sium, and thus improve the corrosion resistance[82,83]. Up to
now, MgeZn based alloys have been reported with good per-
formance. The tensile strength and elongation of a Mge6%Zn
alloy reached to 279.5 MPa and 18.8%, respectively[83]. Mge6%
Zn alloy could be gradually absorbed in vivo at degradation rate
of about 2.32 mm/y, and was harmless to the L-929 cells and the
main organs in animals[83].
3.1.4. MgeRE alloys. As MgeRE alloys possess better me-
chanical performance and corrosion resistance, some new Mge
RE alloys were studied as biodegradable magnesium alloys for
medical application. MgeY alloy was prepared by a zone so-
lidification method, and showed improved corrosion resistance
and mechanical properties[84]. Moreover, MgeGd[85], MgeCe,
MgeNd, MgeLa, etc., were also studied for medical applica-
tions, and among them MgeNd alloy showed a much slower
corrosion rate than the other alloys[86]. MgeYeZn alloy showed
an interesting combination of preferred microstructural, me-
chanical, electrochemical and biological properties, which makes
it very promising for application as a biodegradable implant
material[87,88]. The corrosion resistance of Mge1.2%Nde0.5%
Ye0.5%Zr alloy was improved by addition of 0.4%Ca, however
the stress corrosion behavior was damaged[89].
507
3.1.5. Other biodegradable magnesium alloys. Binary Mg-1X
(wt.%) (X ¼ Al, Ag, In, Mn, Si, Sn, Y, Zn and Zr) alloys were
studied to evaluate the biological behaviors compared with pure
magnesium[90]. It was found that the hemolysis and the amount of
adhered platelets decreased for all the Mg-1X alloys as compared
to the pure magnesium control. Moreover, the biological behavior
of high purity Mge1.2Mne1.0Zn was in vivo evaluated. After 9
and 18 weeks post-implantations, all the magnesium alloy im-
plants were fixed tightly and no inflammation was found[90].
With more studies and corresponding developments of
biodegradable magnesium alloys, some new alloys with
biocompatible elements and better combination of corrosion
resistance and mechanical properties are expected to be applied
in clinic in the future.
3.2. Degradation mechanism of magnesium based metals
Magnesium based metals are generally known to be corroded
in an aqueous environment via an electrochemical reaction,
which produces magnesium hydroxide and hydrogen gas. The
overall corrosion reaction of magnesium in an aqueous envi-
ronment is given below:
MgðsÞ þ 2H2 OðaqÞ ¼ MgðOHÞ2ðsÞ þ H2ðgÞ (1)
It is well known that Cl ions easily induce pitting corrosions
to happen on magnesium alloys. When the chloride concentra-
tion in the corrosive environment rises above 30 mmol/L,
magnesium hydroxide formed as Eq. (1) will continue to react
with magnesium to form a highly soluble magnesium chloride
and thus the degradation rate is increased. HPO4 2 ions can
decrease the corrosion rate of magnesium alloys and the occur-
rence of pitting corrosion is significantly delayed due to the
precipitation of magnesium phosphate. HCO3 ions are
observed to stimulate the corrosion of magnesium alloys during
the early immersion stage, but they can also induce a rapid
passivation on the surface of the alloys, mainly resulting from
the fast precipitation of magnesium carbonate in the corrosion
product layer, which can subsequently completely inhibit the
pitting corrosion. SO4 2 ions were also found to stimulate the
dissolution of magnesium[91]. Proteins such as albumin have
been demonstrated to form a corrosion blocking layer on the
magnesium alloys in the in vitro experiment. This layer can be
enriched with calcium phosphates that concomitantly participate
in the corrosion protection[92]. However, organic compounds,
such as amino acids, promote the dissolution of magnesium[93].
In addition, magnesium alloys are susceptible to stress
corrosion cracking in the chloride-containing environment,
resulting in a sudden catastrophic/premature cracking, which is
so called stress corrosion cracking. Therefore stress corrosion
cracking in the chloride-containing solution for magnesium
based metal implants in a loading-bearing application, such as
coronary stents under the loading of blood vessel and blood flow,
plates and screws for orthopedic fixation under the loading of
body weight and movement, should be in much concern.
3.3. Potential application of magnesium based metals for bone
repairs
Owing to the attractive advantages besides the characteristic
of biodegradation, magnesium based metals have become one of
508 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
the hot spots in metallic biomaterials research for the past 10
years. For application in bone repairs, magnesium based metals
have been widely investigated both in vitro and in vivo, mostly
focused on screws and plates for fixations, and porous scaffolds
as bone filling materials. However since the mechanical prop-
erties of magnesium alloys are still much lower than those of
commonly used titanium alloys and stainless steels for the load
bearing bones, the implants not for load bearing are the currently
potential applications for magnesium based metals.
In addition, the application of magnesium based metals is also
limited by their fast degradation rates inducing hemolysis,
osteolysis, physical stimulation of gas bubble and fast decreases of
mechanical properties. To solve this problem, besides the devel-
opment of new alloys with higher corrosion resistance, surface
modification is considered to be an effective method. Many sur-
face modification methods have been employed for biodegradable
magnesium based metals, such as anodization[94,95], micro-arc
oxidation[96,97], electrodeposition[98,99], phosphating[100,101],
biomimetic treatment[102] etc, and some progresses on reduction
of the degradation rates have been achieved.
Fig. 5 The bioceramics tree and its fruits[104].
4. Biodegradable/Bioresorbable Ceramics
Ceramics have become a diverse class of biomaterials which
were initially used as alternatives to metallic biomaterials in
order to increase the biocompatibility of implants. Bioceramics
are presently used to fill defects in tooth and bones, to fix bone
grafts, fractures and prostheses, and to replace diseased tissues.
According to the reaction between the material and the living
tissue, bioceramics can be classified into three groups: (1) bio-
inert ceramics such as alumina and zirconia, (2) bioactive ce-
ramics such as hydroxyapatite and other calcium phosphate
ceramics, and (3) bioresorbable ceramics[103]. Various bio-
ceramics and their applications are shown in Fig. 5.
4.1. Commonly used bioresorbable ceramics
Bioresorbable ceramics are characterized with gradual disso-
lution of the materials in vivo by the biosystem of the organisms,
and are used for replacements of bone tissues without toxicity
and rejection[105]. Among different bioactive and resorbable
 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
ceramics, calcium phosphate based ceramics such as hydroxy-
apatite (HA), b-tricalcium phosphate (b-TCP) as well as bioac-
tive glass are quite substantially used for long time. Calcium
phosphate ceramics are synthetic scaffolds that have been used in
dentistry since the early of 1970s and in orthopedics since
1980s[106108].
4.1.1. Calcium hydroxyapatite. Hydroxyapatite (HA) is
attributed to the compositions of bioactive and bioresorbable
ceramics, or substances close to it in composition which forms
HA crystals by the reaction with the organism at the implante
biomedium interface[105]. Synthetic HA is produced through a
high-temperature reaction and is a highly crystalline form of
calcium phosphate. The nominal composition of this mixture is
Ca10 (PO4)6(OH)2 with an atomic ratio for calcium-to-
phosphate of 1.67. Synthetic HA is a complete chemical and
crystalochemical analog of bone mineral. This chemical simi-
larity with bone accounts for their osteoconductive potential
and excellent biocompatibility[109111]. Synthetic and natural
HA differ only in structure. Calcium hydroxyapatite/tricalcium
phosphate (60/40) provides a structure or scaffold which can
have a close interface with adjacent bone and have a limited
application in the treatment of load-bearing segmental bone
defects that did not fail at the early stages of implantation[112].
Hydroxyapatite has been established to be an excellent carrier
of osteoinductive growth factors and osteogenic cell pop-
ulations, which greatly add to their utilities as bioactive de-
livery vehicles in the future[113].
Clinical indications are related to specific structural, biological
and biomechanical properties of the bone grafts. HA ceramics
are useful to fill small bone defects after bone tumor resection or
after bone loss in fresh fractures, e.g., in tibia, humerus, calca-
neus, radius and vertebral surgeries, but they are not indicated in
large bone defects[114]. Besides, the bioresorption of HA seems
to be related to its properties. It was reported that HA underwent
a slow degradation, and minimal resorption after an implantation
period of 12 weeks in rabbit’s femora was found[115].
In recent years, there have been efforts in developing the
doped bioceramics materials such as Mg-HA[116], Sr-HA[117], Si-
HA[118], CHA[119] to enhance their mechanical and biological
properties for tissue engineering applications. In addition, Ag-
HA is studied for curing the infected bone defects[120]. Hy-
droxyapatite as a synthetic material, is known for its good
cytocompatibility, but is limited in use due to its moderate to low
solubility in the body and mechanical properties that differ from
surrounding tissues and bones[121]. HA doped with manganese
and/or zinc as bone substitute resulted in a faster resorption
kinetics[122].
4.1.2. Tricalcium phosphate. Like hydroxyapatite, tricalcium
phosphate (TCP) Ca3(PO4)2 is also a bioactive and resorbable
ceramic material. The chemical composition and crystallinity of
the material are similar to those of the mineral phase of bone. It
exists in either a or b-crystalline form. Its biodegradation rate is
higher compared with HA. Degradability occurs by combination
of dissolution and osteoclastic resorption[123].
Tricalcium phosphate implants have been used for two de-
cades as the synthetic bone void fillers in orthopedic and dental
applications[124,125]. The small particle size and the inter-
connected sponge like microporosity are believed to improve
osteoconductive abilities and promote timely resorption
concomitant with the remodeling process[111,126128]. Zhang
et al.[129] reported the bone formation with bone marrow stromal
509
cells (BMSCs) and b-tricalcium phosphate (b-TCP) as the bone
substitute implanted in rat dorsal muscles. Cutright et al. [130]
found 95% absorption of tricalcium phosphate ceramic im-
plants in rat tibias 48 days postoperatively with extensive bone
growth and marrow reformation. Cameron et al.[131] observed
both the toxicity and the bone-ingrowth potential of TCP in
canine model and reported no untoward tissue or systemic re-
action when implanted in cancellous bone. It was rapidly infil-
trated with bone and slowly resorbed. Resorption of these TCPs
was mediated by osteoclastic activity and resorption time vary-
ing between 6 and 24 months[132].
4.1.3. Bioactive glass-ceramics. Certain calcium phosphate
glass-crystalline materials and glasses are also classified as
bioactive ceramics in the scientific and medical literatures, due to
the formation of HA microcrystals on their surfaces upon reac-
tion with the biomedia via strong biochemical bonds with
adjacent bone tissues[133e135]. Glass-crystalline materials may be
considered in essence as ceramics with high concentrations of
glass phase, while bioactive glasses are materials which contain
small amounts of crystalline phase, or nuclei, formed by selec-
tive chemical solution and (or) annealing. The following crys-
talline phases are found in bioactive glass-crystalline materials
and glasses: apatite (general formula Ca10(PO4)6(O,OH,F),
b-wollastonite (b-CaOSiO2), phlogopite ((Na, K)Mg3(AlSiO10)
F2), and witlokite (b-Ca3(PO4)2) [105].
Bioactive glass ceramics (Bio-glass) were first developed by
Hench et al. [136]. This glass was biocompatible, osteoconductive
and bonds to bone without an intervening fibrous connective tissue
interface[137,138]. This material has been widely used for filling
bone defects[139,140] alone and in combination with autogenous
and allogenic cancellous bone graft[141]. Bio-glass is composed
mainly of silica, sodium oxide, calcium oxide and phosphates. The
range of compositions in the Na2OeCaOeP2O5eSiO2 system in
which bioactivity is found is approximately (mole %) 5e17 P2O5,
20e50 CaO, 20e55 SiO2, and 10e50 Na2O.
Many bioactive and resorbable ceramics containing silicate
phase are based on the composition “45S5”, i.e., 45% SiO2. It is
interesting that replacing part of the SiO2 in this composition with
B2O3 (up to 15% B2O3), adding CaF2 up to 12% instead of CaO, or
increasing the amount of crystalline phase by changing the crys-
tallization conditionsdall have little effect on the bioactivity of the
material, i.e., its ability to form a biochemical bond with bone[142].
At the same time the addition of only 3% Al2O3 prevents the
formation of bonding with bone. Small additions of titanium,
tantalum, zirconium, and antimony oxides also decrease the ability
to form an adherent bond with bone[143,144]. For certain bioceramic
compositions, for example the glass-ceramics Cerabone A/W, the
adhesive strength of the bone-implant bond exceeded the strength
of both ceramics and bone[145].
Bioactive glasses have been clinically used for tympanoplastic
reconstruction[146], as filling materials in benign tumor sur-
geries[147], for reconstruction of defects in facial bones[148,149],
for treatment of periodontal bone defects[150,151], in obliteration
of frontal sinuses [152e154], in repairing orbital floor frac-
tures[155,156], in lumbar fusion[157], and for reconstruction of the
iliac crest defect after bone graft harvesting[158].
4.2. Physicochemical and mechanical properties
Table 2 shows typical properties of bioactive and resorbable
HA and TCP ceramics, and also the compositions and properties
of a number of bio-glass crystalline materials and bio-
510 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513

Table 2 Composition and mechanical properties of bioactive and resorbable ceramics[159]

Parameter Ceramics Bioglass Glass-ceramic

HA TCP 45S5 S45PZ Ceravital Cerabone A/W I1mappant Biovert

Comosition, mass%
Na2O e e 24.5 24 5e10 0 4.6 3e8
K2O e e 0 e 0.5e3.0 0 0.2 3e8
MgO e e 0 e 2.5e5.0 4.6 2.8 2e21
CaO e e 24.5 22 30e35 44.7 31.9 10e34
Al2O3 e e 0 e 0 0 0 8-15
SiO2 e e 45.0 45 40e50 34.0 44.3 19e54
P2O5 e e 6.0 7 10e50 16.2 11.2 2e10
CaF2 e e 0 e e 0.5 5.0 3e23
B2O3 e e 0 2 e e e
Phase Apatite Witlokite Glass Glass Apatite, Apatite, Apatite, Apatite,
glass b-wollastonite, b-wollastonite, phlogopite
glass glass glass
Density, g/cm3 3.16 3.07 2.66 e e 3.07 e 2.8
Hardness, HV 600 e 460 e 680 e 500 460
Strength, MPa:
compressive bend 500e1000 460e680 e e 500 1080 e 500
115e200 140e154 110e140 e e 215 160 500
Young modulus, GPa 80e110 33e90 35 e 100e150 218 e 70e88
Fracture toughness 1.0 e e e 2.0 2.5 0.5e1.0 e
K1c, MPa$m1/2

glasses[159].The strengths of bioactive ceramics are substantially 4.3. Degradation mechanism

lower than those of bio-inert ones. The highest strength is found
in non-porous HA and in the glass-ceramics Cerabone A/W, but
the bend strength and crack resistance of these materials are 5e7
times lower than those of high-strength ZrO2 ceramics. HA
generally provides limited biomechanical support due to their
low tensile resistance, and TCP is less fragile than HA. There are
no relevant data on structural or biomechanical properties of
bioactive glasses in the literatures, but they show a superior
mechanical strength compared with calcium phosphate products
as a result of strong graft-bone bonding.
The degradation of bioresorbable ceramics was assumed to
take place by solution-driven and cell-mediated processes[160].
The chemical composition, physical characteristics and crystal
structures certainly play important roles in the biological
behavior of ceramics[161e163]. After implantation, bioresorbable
ceramics undergo cellular degradation and are progressively
replaced by lamellar true bone characterized by physiological
bone remodeling. Cells involved in degradation/resorption of
ceramics intervene via two main mechanisms: phagocytosis and

Table 3 Mechanical properties of biodegradable polymer, ceramics and magnesium alloys[92]

Tissue/material Compressive Tensile strength, E-modulus, GPa Tensile yield Elongation (A)at
strength, MPa MPa strength, MPa break, %

Cortical bonea 164e240 35e283 5e23 1.07e2.10

Cancellous bonea 1.5e38 10e1570 (MPa)
Synthetic Hydroxyapatite 100e900 40e200 70e120
Bioactive glass 40e60 35e35
DL-PLA 29e35 1.9e2.4 5e6
AZ91E-F sand cast 97 165 45 97 2.5
AZ91E-F HPDC 165 230 45 150 3
AZ91E-GAE 457 45 517 11.1
AZ31 extruded 83e97 241e260 165e200 12e16
AZ31 sheet 110e180 255e290 150e220 15e21
AZ31GAE 445 424 11.5
LAE442 247 148 18
WE43A-T6 250 162 2
WE43-B 345 220 2
WE43 extruded 277 198 17
AZ91þ2Ca-GAE 452 427 5.4
AZ91þ2Ca 147 1.7
Mg0.8Ca 428
Mg(0e4)Ca 210e240
AM50A-F 113 210 10
AM60B-F 130 225 8
 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
extracellular acidification (resorption). These two processes are
modulated by various parameters, such as the implantation site
and the presence of various proteins (cytokines, extracellular
matrix protein). The cells implicated in this degradation process
(mesenchymal cells, monocytes/macrophages, osteoclasts) could
intervene directly or indirectly through their cytokines/growth
factor secretions and their sensitivity to the same substances
which modulate cellular activities[164,165].
4.4. Applications of bioresorbable ceramics in bone repair
Based on the performances above, bioactive and resorbable
ceramics are used in all types of bone reconstruction, in partic-
ular for the fabrication of implants which densely fuse with bone
(for example in skull restorations after operations or trauma),
tooth-root implants, biological tooth fillings, cure of diseases of
the periodontia (tissue around teeth), maxillofacial reconstruc-
tion, grafting and stabilizing skull bone, joint reconstruction, for
the endoprosthesis of hearing aids, cosmetic eye prostheses,
etc[166]. Resorbable ceramics also aid in the restoration of ten-
dons, ligaments, small blood vessels, and nerve fibers[167].
Among these products, bone graft substitutes are widely used.
Reports on clinical applications are found for Depuy Spine
ConduitÒ (TCP), Medtronic MasterGraftÒ (HA, TCP), Stryker
VitossÒ (TCP), Synthes ChronOSÒ, NorianÒ SRSÒ (calcium
phosphate), Stryker CortossÒ (bioactive glass), etc.
5. Summary
Biodegradable materials for bone repairs attract more and
more attention in the field of biomaterials since their bio-
degradabilities to avoid the second surgeries and reduce the pain
and economic cost for patients. Biodegradable polymers and
ceramics are already applied in clinic and biodegradable mag-
nesium based metals are a class of new biodegradable materials
still in development. It is expected that more biodegradable
materials can be developed for more selections in clinic. From
the above review, it can be seen that these three types of
biodegradable materials have their own advantages which should
be recognized and compared when applied to bone repairs.
As shown in Table 3, the mechanical properties of three
different biodegradable materials for bone repairs are quite
different. The tensile strength of magnesium alloy is obviously
higher than those of polymer (DL-PLA) and ceramic (Hy-
droxyapatite, Bioactive glass). The elongation of magnesium
alloy is also higher than that of DL-PLA, and the ceramic shows
the highest brittleness.
Degradation mechanism is one of the important characters
for biodegradable materials, which also affects the evolution of
mechanical properties during degradation. Most of the
degradable polymers degrade by hydrolysis and enzymolysis
from macromolecule to small molecular, and eventually to
carbon dioxide and water. The mechanical strength of most
polymers decreases slowly at the initial stage of degradation,
while having sharply decrease when body degradation happens.
Magnesium based metals degrade by corrosion in body fluid
from the surface or pits, with comparatively high degradation
rate at the initial stage and becomes slower with time. The
mechanical strength of magnesium alloys keeps stable during
degradation since their inner structures maintain unchanged,
while the load retention decreases[168,169]. The ceramics
degrade by solution-driven and cell-mediated processes and are
progressively replaced by lamellar true bone characterized by
511
physiological bone remodeling, however the mechanical evo-
lution was seldom reported.
The biological behaviors of biodegradable polymers and mag-
nesium alloys were compared in the previous studies. It was
proved that more new bones were found around the magnesium
alloy implant than the polymer implant, showing better biological
and bioactive behaviors of magnesium alloy, which is attributed to
the biocompatible and bioactive degradation products of magne-
sium alloy, e.g., Mg2þ, however the acidic degradation products
of polymer is possible to induce inflammation.
Since the mechanical properties, degradation mechanism and
biological behaviors are different for the three types of biode-
gradable materials, their applications for implants should be
individually designed to exert their own advantages, and in some
applications the competitions among the biodegradable materials
are also possible.
Acknowledgments
The authors would like to thank the financial support of the
National Basic Research Program of China (973 Program,
No.2012CB619101).
REFERENCES
[1] C.F.L. Chu, A. Lu, M. Liszkowski, R. Sipehia, BBA-GEB Sub-
jects 1472 (1999) 479e485.
[2] B.J.R.F. Bolland, J.M. Kanczler, P.J. Ginty, S.M. Howdle, K.M.
Shakesheff, D.G. Dunlop, R.O.C. Oreffo, Biomaterials 29 (2008)
3221e3227.
[3] D.B. Thordarson, G. Hurvitz, Foot Ankle International 23 (2002)
1003e1007.
[4] R. Suuronen, L. Wessman, M. Mero, P. Tormala, J. Vasenius, E.
Partio, K. Vihtonen, S. Vainionpaa, J. Mater. Sci. Mater. Med. 3
(1992) 288e292.
[5] A. Weiler, H.J. Windhagen, M.J. Raschke, A. Laumeyer, R.F.G.
Hoffmann, Am. J. Sport Med. 26 (1998) 119e128.
[6] B.L. Eppley, M. Reilly, J. Craniofac. Surg. 8 (1997) 116e120.
[7] G. Daculsi, N. Passuti, S. Martin, C. Deudon, R. LeGeros, S.
Raher, J. Biomed. Mater. Res. 24 (1990) 379e396.
[8] B. Spiessl, C. Bassetti, New Concepts in Maxillofacial Bone
Surgery, Springer-Verlag, 1976.
[9] J. Disegi, L. Eschbach, Injury 31 (2000) 2e6.
[10] M.O. Tachdjian, Pediatric Orthopedics, Saunders, Philadelphia, 1990.
[11] S.M. Kurtz, J.N. Devine, Biomaterials 28 (2007) 4845e4869.
[12] R. LeGeros, Adv. Dent. Res. 2 (1988) 164e180.
[13] L. Reclaru, J.-M. Meyer, Biomaterials 19 (1998) 85e92.
[14] B.H. Fellah, O. Gauthier, P. Weiss, D. Chappard, P. Layrolle,
Biomaterials 29 (2008) 1177e1188.
[15] R. Brosnahan, L. A. Small, J. A. Bearcroft, Artificial bone graft
implant, US Patent, No.6149688, 2000.
[16] H.J. Mankin, F.S. Fogelson, A.Z. Thrasher, F. Jaffer, New Engl. J.
Med. 294 (1976) 1247e1255.
[17] J.F. Mano, R.A. Sousa, L.F. Boesel, N.M. Neves, R.L. Reis,
Compos. Sci. Technol. 64 (2004) 789e817.
[18] R.A. Sousa, R.L. Reis, A.M. Cunha, M.J. Bevis, Compos. Sci.
Technol. 63 (2003) 389e402.
[19] N. Ashammakhi, P. Rokkanen, Biomaterials 18 (1997) 3e9.
[20] P.B. Maurus, C.C. Kaeding, Oper. Techn. Sport Med. 12 (2004)
158e160.
[21] W.S. Pietrzak, D.R. Sarver, M.L. Verstynen, J. Craniofac. Surg. 8
(1997) 87e91.
[22] H.M. Wong, K.W.K. Yeung, K.O. Lam, V. Tam, P.K. Chu, K.D.
K. Luk, K. Cheung, Biomaterials 31 (2010) 2084e2096.
[23] E. Ma, J. Xu, Nat. Mater. 8 (2009) 855e857.
[24] F. Witte, H. Ulrich, M. Rudert, E. Willbold, J. Biomed. Mater. Res.
A 81A (2007) 748e756.
512 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
[25] F. Witte, H. Ulrich, C. Palm, E. Willbold, J. Biomed. Mater. Res.
A 81A (2007) 757e765.
[26] R.A. Miller, J.M. Brady, D.E. Cutright, J. Biomed. Mater. Res. 11
(2004) 711e719.
[27] X. Wen, P.A. Tresco, Biomaterials 27 (2006) 3800e3809.
[28] H. Shin, S. Jo, A.G. Mikos, Biomaterials 24 (2003) 4353e4364.
[29] W.S. Koegler, L.G. Griffith, Biomaterials 25 (2004) 2819e2830.
[30] B.C. Benicewicz, P.K. Hopper, J. Bioact. Compat. Pol. 6 (1991)
64e94.
[31] C.W. Lou, C.H. Yao, Y.S. Chen, T.C. Hsieh, J.H. Lin, W.H. Hsing,
Text. Res. J. 78 (2008) 958e965.
[32] D. J. Casey, L. Rosati, P. K. Jarrett, L. T. Lehmann, Bioabsorbable
surgical suture coating, US Patent, No. 4857602, 1989.
[33] H. J. F. Sinn, Package and method of loading for resilient surgical
sutures, US Patent, No.5249671, 1993.
[34] R. Datta, M. Henry, J. Chemical. Technol. Biot. 81 (2006) 1119e
1129.
[35] R. Mehta, V. Kumar, H. Bhunia, S. Upadhyay, J. Macromal. Sci.
C. 45 (2005) 325e349.
[36] D. Garlotta, J. Polym. Environ. 9 (2001) 63e84.
[37] R. Kulkarni, K. Pani, C. Neuman, F. Leonard, Arch. Surg. 93
(1966) 839e843.
[38] R. Kulkarni, E. Moore, A. Hegyeli, F. Leonard, J. Biomed. Mater.
Res. 5 (1971) 169e181.
[39] E.T.H. Vink, K.R. Rabago, D.A. Glassner, P.R. Gruber, Polym.
Degrad. Stabil. 80 (2003) 403e419.
[40] A. Daniels, M.K.O. Chang, K.P. Andriano, J. Heller, J. Appl.
Biomater. 1 (2004) 57e78.
[41] A. Reed, D. Gilding, Polymer 22 (1981) 494e498.
[42] K.A. Athanasiou, G.G. Niederauer, C. Agrawal, Biomaterials 17
(1996) 93e102.
[43] J.K. Francis Suh, H.W.T. Matthew, Biomaterials 21 (2000) 2589e
2598.
[44] E. Sachlos, J. Czernuszka, Eur. Cell. Mater. 5 (2003) 39e40.
[45] K. Athanasiou, J. Schmitz, C. Agrawal, Tissue Eng. 4 (1998) 53e63.
[46] I. McVicar, P. Hatton, I. Brook, Brit. J. Oral Max. Surg. 33 (1995)
220e223.
[47] P.B. Messersmith, E.P. Giannelis, J. Polym. Sci. Chem. 33 (1995)
1047e1057.
[48] G. Jimenez, N. Ogata, H. Kawai, T. Ogihara, J. Appl. Polym. Sci.
64 (1997) 2211e2220.
[49] P. Xing, L. Dong, Y. An, Z. Feng, M. Avella, E. Martuscelli,
Macromolecules 30 (1997) 2726e2733.
[50] L.N. Novikova, J. Pettersson, M. Brohlin, M. Wiberg, L.N.
Novikov, Biomaterials 29 (2008) 1198e1206.
[51] M. Yokouchi, Y. Chatani, H. Tadokoro, K. Teranishi, H. Tani,
Polymer 14 (1973) 267e272.
[52] G.J.M. de Koning, P.J. Lemstra, Polymer 34 (1993) 4089e4094.
[53] M. Yasin, S. Holland, A. Jolly, B. Tighe, Biomaterials 10 (1989)
400e412.
[54] Y. Azuma, N. Yoshie, M. Sakurai, Y. Inoue, R. Chujo, Polymer 33
(1992) 4763e4767.
[55] M. Avella, E. Martuscelli, P. Greco, Polymer 32 (1991) 1647e
1653.
[56] M. Avella, E. Martuscelli, M. Raimo, Polymer 34 (1993) 3234e
3240.
[57] R. Pearce, G. Brown, R. Marchessault, Polymer 35 (1994) 3984e
3989.
[58] R. Pearce, J. Jesudason, W. Orts, R. Marchessault, S. Bloember-
gen, Polymer 33 (1992) 4647e4649.
[59] M. Canetti, P. Sadocco, A. Siciliano, A. Seves, Polymer 35 (1994)
2884e2887.
[60] P. Sadocco, M. Canetti, A. Seves, E. Martuscelli, Polymer 34
(1993) 3368e3375.
[61] K.K. Yang, X.L. Wang, Y.Z. Wang, J. Macromal. Sci. C. 42 (2002)
373e398.
[62] A. Gertzman, D. R. Thompson, Annealed polydioxanone surgical
device and method for producing the same, US Patent, No.
4620541, 1986.
[63] F. V. Mattei, N. Doddi, Synthetic absorbable hemostatic compo-
sition, US Patent, No.4443430, 1984.
[64] D. Fiz, Bone fixation device, US Patent, No.5951558, 1999.
[65] A. Pezzin, V. Ekenstein, G. Alberda, C. Zavaglia, G. Ten Brinke,
E. Duek, J. Appl. Polym. Sci. 88 (2003) 2744e2755.
[66] W. Bai, D. Chen, Z. Zhang, Q. Li, D. Zhang, C. Xiong, J. Biomed.
Mater. Res. B 90 (2009) 945e951.
[67] A. Pezzin, E. Duek, Polym. Degrad. Stabil. 78 (2002) 405e411.
[68] W. Bai, D. Chen, Q. Li, H. Chen, S. Zhang, X. Huang, C.D.
Xiong, J. Polym. Res. 16 (2009) 471e480.
[69] I. Armentano, M. Dottori, E. Fortunati, S. Mattioli, J.M. Kenny,
Polym. Degrad. Stabil. 95 (2010) 2126e2146.
[70] L. Fambri, A. Pegoretti, R. Fenner, S. Incardona, C. Migliaresi,
Polymer 38 (1997) 79e85.
[71] J.W. Leenslag, A.J. Pennings, R.R.M. Bos, F.R. Rozema, G.
Boering, Biomaterials 8 (1987) 70e73.
[72] M. Zignani, T. Le Minh, S. Einmahl, C. Tabatabay, J. Heller, J.
Anderson, R. Gurny, Biomaterials 21 (2000) 1773e1778.
[73] M.P. Staiger, A.M. Pietak, J. Huadmai, G. Dias, Biomaterials 27
(2006) 1728e1734.
[74] P. Zartner, R. Cesnjevar, H. Singer, M. Weyand, Catheter. Cardio.
Inte. 66 (2005) 590e594.
[75] X.H. Xu, M.Q. Guo, L. Cao, P. Lu, Y. Liu, J. Mater. Sci-Mater. M.
22 (2011) 1735e1740.
[76] F. Witte, I. Abeln, E. Switzer, V. Kaese, A. Meyer-Lindenberg,
H. Windhagen, J. Biomed. Mater. Res. A 86A (2008) 1041e
1047.
[77] H. Kuwahara, Y. Al-Abdullat, N. Mazaki, S. Tsutsumi, T. Aizawa,
Mater. Trans. 42 (2001) 1317e1321.
[78] Y.B. Ren, J.J. Huang, K. Yang, B.C. Zhang, Z.M. Yao, H. Wang,
Acta Metall. Sin 41 (2005) 1228e1232 (in Chinese).
[79] N. Hort, Y. Huang, D. Fechner, M. Stormer, C. Blawert, F. Witte,
C. Vogt, H. Drucker, R. Willumeit, K.U. Kainer, F. Feyerabend,
Acta Biomater. 6 (2010) 1714e1725.
[80] Y.F. Zheng, Z.J. Li, X.N. Gu, S.Q. Lou, Biomaterials 29 (2008)
1329e1344.
[81] C.J. Boehlert, K. Knittel, Mat. Sci. Eng. A Struct. 417 (2006)
315e321.
[82] X.N. Zhang, S.X. Zhang, J.A. Li, Y. Song, C.L. Zhao, C.Y. Xie,
Y. Zhang, H.R. Tao, Y.H. He, Y. Jiang, Y.J. Bian, Mat. Sci. Eng. C
-Mat. 29 (2009) 1907e1912.
[83] X.N. Zhang, S.X. Zhang, C.L. Zhao, J.A. Li, Y. Song, C.Y. Xie, H.
R. Tao, Y. Zhang, Y.H. He, Y. Jiang, Y.J. Bian, Acta Biomater. 6
(2010) 626e640.
[84] Q.M. Peng, Y.D. Huang, L. Zhou, N. Hort, K.U. Kainer, Bio-
materials 31 (2010) 398e403.
[85] Y. Nakamura, Y. Tsumura, Y. Tonogai, T. Shibata, Y. Ito, Fund.
Appl. Toxicol. 37 (1997) 106e116.
[86] Y.F. Zheng, X.N. Gu, JOM 63 (2011) 105e108.
[87] A.C. Hänzi, I. Gerber, M. Schinhammer, J.F. Löffler, P.J. Uggo-
witzer, Acta Biomater. 6 (2010) 1824e1833.
[88] P.J. Uggowitzer, A.C. Hanzi, A.S. Sologubenko, Int. J. Mater. Res.
100 (2009) 1127e1136.
[89] E. Aghion, G. Levy, J. Mater. Sci. 45 (2010) 3096e3101.
[90] X.N. Gu, Y.F. Zheng, Y. Cheng, S.P. Zhong, T.F. Xi, Biomaterials
30 (2009) 484e498.
[91] Y.C. Xin, K.F. Huo, H. Tao, G.Y. Tang, P.K. Chu, Acta Biomater.
4 (2008) 2008e2015.
[92] F. Witte, N. Hort, C. Vogt, S. Cohen, K.U. Kainer, R. Willumeit,
F. Feyerabend, Curr. Opin. Solid St. M 12 (2008) 63e72.
[93] A. Yamamoto, S. Hiromoto, Mat. Sci. Eng. C Mat. 29 (2009)
1559e1568.
[94] G. Song, Corros. Sci. 49 (2007) 1696e1701.
[95] D. Xue, Y. Yun, M.J. Schulz, V. Shanov, Mat. Sci. Eng. C Mat. 31
(2011) 215e223.
[96] X. Gu, N. Li, W. Zhou, Y. Zheng, X. Zhao, Q. Cai, L. Ruan, Acta
Biomater. 7 (2011) 1880e1889.
[97] X. Lin, L. Tan, Q. Zhang, K. Yang, Z. Hu, J. Qiu, Y. Cai, Acta
Biomater. http://dx.doi.org/10.1016/j.actbio.2012.12.016.
 L. Tan et al.: J. Mater. Sci. Technol., 2013, 29(6), 503e513
[98] C. Wen, S. Guan, L. Peng, C. Ren, X. Wang, Z. Hu, Appl. Surf.
Sci. 255 (2009) 6433e6438.
[99] Y. Song, S. Zhang, J. Li, C. Zhao, X. Zhang, Acta Biomater. 6
(2010) 1736e1742.
[100] L. Xu, E. Zhang, K. Yang, J. Mater. Sci. Mater. Med. 20 (2009) 859e
867.
[101] F. Geng, L. Tan, X. Jin, J. Yang, K. Yang, J. Mater. Sci. Mater.
Med. 20 (2009) 1149e1157.
[102] Y.J. Lu, L.L. Tan, H.L. Xiang, B.C. Zhang, K. Yang, Y.D. L,
J. Mater. Sci. Tech. 28 (2012) 636e641.
[103] G. Dominique, Biomechanics and Biomaterials in Orthopedics,
Springer, Heidelberg, 2004, pp. 22e23.
[104] E. Truumees, H.N. Herkowitz, U.P.O.J. 12 (1999) 77e88.
[105] V.A. Dubok, Powder Metal. Met. Ceramic 39 (2000) 381e394.
[106] D.J. Hak, J. Am. Acad. Orthop. Sur. 15 (2007) 525e536.
[107] S. Larsson, T.W. Bauer, Clin. Orthop. Relat. R. 395 (2002) 23e32.
[108] M. Bohner, Injury 31 (2000) 37e47.
[109] E. Erbe, J. Marx, T. Clineff, L. Bellincampi, Eur. Spine J. 10
(2001) 141e146.
[110] H.L. Dai, X.Y. Wang, Y.C. Han, X. Jiang, S.P. Li, J. Mater. Sci.
Tech. 27 (2011) 431e436.
[111] S.K. Ghosh, S.K. Nandi, B. Kundu, S. Datta, D.K. De, S.K. Roy,
D. Basu, J. Biomed. Mater. Res. B 86 (2008) 217e227.
[112] C. Balcik, T. Tokdemir, A. senkoylu, N. Koc, M. Timucin, S. Akin,
P. Korkusuz, F. Korkusuz, Acta Biomater. 3 (2007) 985e996.
[113] T. Noshi, T. Yoshikawa, M. Ikeuchi, Y. Dohi, H. Ohgushi, K.
Horiuchi, M. Sugimura, K. Ichijima, K. Yonemasu, J. Biomed.
Mater. Res. 52 (2000) 621e630.
[114] R. Quarto, M. Mastrogiacomo, R. Cancedda, S.M. Kutepov, V.
Mukhachev, A. Lavroukov, E. Kon, M. Marcacci, New Engl. J.
Med. 344 (2001) 385e386.
[115] J. Brandt, S. Henning, G. Michler, W. Hein, A. Bernstein, M.
Schulz, J. Mater. Sci. Mater. Med. 21 (2010) 283e294.
[116] H.-S. Ryu, K.S. Hong, J.-K. Lee, D.J. Kim, J.H. Lee, B.-S. Chang,
D.-h. Lee, C.-K. Lee, S.-S. Chung, Biomaterials 25 (2004) 393e401.
[117] C.M. Mardziah, I. Sopyan, S. Ramesh, Trends Biomater. Artif.
Organs 23 (2009) 105e113.
[118] E. Thian, J. Huang, S. Best, Z. Barber, W. Bonfield, J. Biomed.
Mater. Res. B 76 (2006) 326e333.
[119] D.M. Ibrahim, A.A. Mostafa, S.I. Korowash, Chem. Cent. J. 5
(2011) 74e86.
[120] M. Jelinek, T. Kocourek, K. Jurek, J. Remsa, J. Miksovsky, M.
Weiserova, J. Strnad, T. Luxbacher, Appl. Phys. A-Mater. 101
(2010) 615e620.
[121] M. Santos, P. Valerio, A. Goes, M. Leite, L. Heneine, H. Mansur,
Biomed. Mater. 2 (2007) 135e141.
[122] J.L. Irigaray, H. Oudadesse, E. Jallot, V. Brun, G. Weber, P. Frays-
sinet, Materials in clinical applications, World ceramics congress and
forum on new materials, Florence, Italy, 28 (1999) 399e403.
[123] G. Daculsi, R. LeGeros, M. Heughebaert, I. Barbieux, Calcified
Tissue Int. 46 (1990) 20e27.
[124] D.J. Hak, J. Am. Acad. Orthop. Surg. 15 (2007) 525e536.
[125] S. Shigaku, F. Katsuyuki, Jikeikai Med. J. 52 (2005) 47e54.
[126] E.Erbe, T.Clineff, M.Lavagnino, L.Dejardin, S Arnoczky, In:
Annual Meeting of the Orthopaedic Research Society, San Fran-
cisco, California, U.S., February 25e28. 2001.
[127] K.A. Hing, L.F. Wilson, T. Buckland, Spine J. 7 (2007) 475e490.
[128] S.K. Nandi, S.K. Ghosh, B. Kundu, D.K. De, D. Basu, Small
Ruminant Res. 75 (2008) 144e153.
[129] M. Zhang, K. Wang, Z. Shi, H. Yang, X. Dang, W. Wang, J. Plast.
Reconstr. Aes. 63 (2010) 227e232.
[130] D.E. Cutright, S.N. Bhaskar, J.M. Brady, L. Getter, W.R. Posey,
Oral Surg. Oral Med. O. 33 (1972) 850e856.
[131] H.U. Cameron, I. Macnab, R.M. Pilliar, J. Biomed. Mater. Res. 11
(1977) 179e186.
[132] M. Bohner, Eur. Spine J. 10 (2001) 114e121.
[133] L.L. Hench, J. Wilson, An Introduction to Ceramics, World Sci-
entific, London, 1993.
[134] L.L. Hench, J.K. West, Life Chem. Rep. 10 (1996) 187e241.
513
[135] S.D. Cook, K.A. Thomas, J.F. Kay, M. Jarcho, Clin. Orthop.
Relat. R. 230 (1998) 303e312.
[136] L.L. Hench, R.J. Splinter, W. Allen, T. Greenlee, J. Biomed.
Mater. Res. 5 (2004) 117e141.
[137] M. Dusková, Z. Smahel, M. Vohradník, M. Tvrdek, J. Mazánek,
J. Kozák, Aesthetic. Plast. Surg. 26 (2002) 274e283.
[138] H. Zhang, X.-J. Ye, J.-S. Li, Biomed. Mater. 4 (2009), 045007 1e7.
[139] M. Vogel, C. Voigt, U.M. Gross, C.M. Muller-Mai, Biomaterials
22 (2001) 357e362.
[140] S.K. Nandi, B. Kundu, S. Datta, D.K. De, D. Basu, Res. Vet. Sci.
86 (2009) 162e173.
[141] H. Dorea, R. McLaughlin, H. Cantwell, R. Read, L. Armbrust, R.
Pool, J. Roush, C. Boyle, Vet. Comp. Orthop. Traumatol. 18
(2005) 157e168.
[142] U. Gross, R. Kinne, H.-J. Schmitz, V. Strunz, CRC Crit. Rev.
Biocompat. 4 (1988) 155e179.
[143] U. Gross, V. Strunz, J. Biomed. Mater. Res. 19 (2004) 251e271.
[144] U. Gross, J. Brandes, V. Strunz, I. Bab, J. Sela, J. Biomed. Mater.
Res. 15 (1981) 291e305.
[145] T. Yamamuto, L. L.Hench, J. Wilson, Bioactive Glasses and
GlasseCeramics: Handbook on Bioactive Ceramics, Vol. 1, CRC
Press, Boca Raton, Florida, 1990.
[146] R. Reck, Laryngoscope 93 (1983) 196e199.
[147] J. Heikkila, K. Mattila, O. Andersson, A. Yli-Urpo, A. Aho,
Bioceramics 8 (1995) 35e40.
[148] E. Suominen, J. Kinnunen, Scand. J. Plast. Surg. Hand Surg. 30
(1996) 281e289.
[149] I. Kinnunen, K. Aitasalo, M. Pollonen, M. Varpula, J. Cranio.
Maxill. Surg. 28 (2000) 229e234.
[150] J.H. Villaca, A.B. Novaes Jr., S.L. S. d. Souza, M. Taba Jr., G.O.
Molina, T.L. Lamano Carvalho, Braz. Dent. J. 16 (2005) 67e74.
[151] J.A. Leonetti, H.M. Rambo, R.R. Throndson, Implant Dent. 9
(2000) 177e182.
[152] J. Suonpaa, J. Sipila, K. Aitasalo, J. Antila, K. Wide, Acta Oto-
laryngol. 117 (1997) 181e183.
[153] M. Peltola, Acta Oto-laryngol. 120 (2000) 167e169.
[154] M.J. Peltola, J.T. Suonpaa, H. Andersson, H.S. Maattanen, K.M.
Aitasalo, A. Yli-Urpo, P.J. Laippala, J. Biomed. Mater. Res. 53
(2000) 161e166.
[155] I. Kinnunen, K. Aitasalo, M. Pollonen, M. Varpula, J. Cranio-
maxillofac. Surg. 28 (2000) 229e234.
[156] K. Aitasalo, I. Kinnunen, J. Palmgren, M. Varpula, J. Oral Maxil.
Surg. 59 (2001) 1390e1394.
[157] K. Ido, Y. Asada, T. Sakamoto, R. Hayashi, S. Kuriyama, Spinal
Cord. 38 (2000) 315e318.
[158] S. Asano, K. Kaneda, S. Satoh, K. Abumi, T. Hashimoto, M.
Fujiya, Eur. Spine J. 3 (1994) 39e44.
[159] P.V. Giannoudis, H. Dinopoulos, E. Tsiridis, Injury 36 (2005) 20e27.
[160] J.D. Lu, Michel, D. Jacques, J. Biomed. Mater. Res. B 63 (2002)
408e412.
[161] S. Radin, P. Ducheyne, J. Biomed. Mater. Res. 28 (1994) 1303e1309.
[162] G.K. De, Bioceramics: Material Characteristics versus in Vivo
Behavior, Academy of Sciences, New York, 1988, pp. 227e233.
[163] R. Li, A. Clark, L. Hench, J. Appl. Biomater. 2 (2004) 231e239.
[164] S. Wenisch, J. Stahl, U. Horas, C. Heiss, O. Kilian, K. Trinkaus, A.
Hild, R. Schnettler, J. Biomed. Mater. Res. A 67 (2003) 713e718.
[165] D. Heymann, G. Pradal, M. Benahmed, Histol. Histopathol. 14
(1999) 871e877.
[166] S.F. Hulbert, J.C. Bokros, L.L. Hench, J. Wilson, G. Heimke.
Ceramics in clinical applications: past, present and future. In:
Vincenzini P, editor. High tech ceramics. Amsterdam,
Netherlands: Elsevier, 1987, pp. 189e213.
[167] J. Black, Ceramics and Composites. In: Orthopedic Biomaterials
in Research and Practice, Churchill Livingston, Inc., N.Y., 1988,
pp. 191e211.
[168] Q. Wang, L. Tan, W. Xu, B. Zhang, K. Yang, Mat. Sci. Eng. B-
Adv 176 (2011) 1718e1726.
[169] T. Yan, T. Tan, D. Xiong, X. Liu, B. Zhang, K. Yang, Mat. Sci.
Eng. C-Mater. 30 (2010) 740e748.