Abstract—during the last decades, bone tissue repair and
regeneration have been increasing interest in the clinical
therapy scientific field, and with the development of materials,
biology and tissue engineering, the bone tissue engineering has
been as an efficient method to treat bone defects. This review
summarizes several aspects related to bone tissue engineering
for bone repair and regeneration: the biomaterials in the bone
tissue engineering, the stem cell behavior in bone tissue
engineering, and the development of biomaterials and bone
tissue engineering. We also highlight several latest
advancements in bone tissue engineering. Finally, a brief
summary of the bone tissue engineering challenges in the field
are provided with suggestions for future research directions.
I. INTRODUCTION
ONES are important structural components for the
vertebrates, which is composed of 60% hydroxyapatite,
10% water and 30% collagen proteins. Bones play important
roles to provide mechanical support for locomotion,
protecting vital organs, and regulating the metabolism of
calcium and phosphorus, and so on. All these functions
requires a healthy bone balance system [1]. However,
millions of people in the world suffer from bone defects due
to many reasons, including trauma, tumor, bone diseases,
congenital defects and aging. These defects are increasingly
becoming the major clinical cases.
The biomaterials are indispensable in the bone repair
therapies; recent advances in the bone repair research have
highlighted the cell-material composite of tissue engineering
which provide the unique self-repair capacity to remodel.
Once implanted, the cell-material composite help the body to
heal itself [2].The constructs are seeded with stem cells,
usually derived from the bone marrow, and then different into
the bone cells under the process of proliferation and
Manuscript received Juny 22, 2011. This work was supported in part by
the Chongqing University of Science and Technology under Grant
CK2010B18.
First Author, Wenfeng Xu, was with the Department of Chemical and
Environmental Engineering, Chongqing University of Art and Science,
Chongqing, China, 402160 (corresponding phone: 023-49682200; fax:
023-49682200, e-mail: xwf_228@163.com).
Second Author, Xiaoling Liao﹡, was the paper’s corresponding author
with the Institute of Biomaterials and Living cell Imaging, Chongqing
University of Science and Technology, Chongqing, China,
401331(corresponding phone: 023-65023701, fax: 023-65023701; e-mail:
zxc_228@163.com).
Third Author, Bo Li, was with the Institute of Biomaterials and Living
cell Imaging, Chongqing University of Science and Technology, Chongqing,
China,401331(corresponding phone: 023-65023701, fax: 023-65023701;
e-mail: leewave@126.com).
Fourth Author, was with the Institute of Biomaterials and Living cell
Imaging, Chongqing University of Science and Technology, Chongqing,
China,400050(corresponding phone: 023-65023701, fax: 023-65023701).
differentiation in vitro conditions [3]. The new bone tissue
regeneration is charged by these bone cells under tightly
controlled microenvironment including chemical and
mechanical stimuli, for example, the surface chemical and
physical characteristics of the scaffold, the shear stress of the
humour, and so on [4].
In this paper, we summarize and provide an overview of
published studies on the biomaterials in the bone tissue
engineering, the stem cell behavior in bone tissue
engineering. We also highlight several latest advancements in
bone tissue engineering. Finally, a brief summary of the bone
tissue engineering challenges in the field are provided with
suggestions for future research directions.
II. BIOMATERIALS FOR BONE TISSUE ENGINEERING
Although slight bone fractures can be easily self-repaired,
serious bone defects or diseases (i.e., comminuted fracture,
osteoporotic and cartilaginous tissues) are difficult to
regenerate and remodel by itself-healing [5]. In this case,
surgery is often required to implant bone graft or artificial
materials at the site of injury or disease [6]. According to
statistics, there are more than 12 million operations requiring
bone substitutes in our world alone each year and the demand
continues to rise drastically. For example, there will be a
174% increase for first-time total hip replacements, and a
673% increase for first-time total knee replacements by the
year 2030 (AAOS 2006c). Such statistics does not include the
steadily growing number of revision surgeries resulted from
the average lifespan (only 10 to 15 years) of an orthopedic
implant [7]. It is clear that the bone implants are becoming a
highly demanded resource for the clinical needs, which will
have significant socio-economic benefits over worldwide.
The traditional bone repair procedure involves the use of
autografts (from the patient iliac crest) and allografts (from
the cadaver bone) [8]. Autograft is still considered as the gold
standard in the reconstruction of bone defects until now,
because it has the structural stability and natural osteogenic
ability [9]. Although the autograft and allograft procedures
have been fairly successful, there are serious limitations such
as limited supply of donor bone tissue, unpredictable
rejection characteristics, infection and donor site morbidity
[10]. Particularly, large bone defects are a major clinical
problem since autologous bone grafts are not available in up
to 40% of these patients [11]. Therefore, there is a pressing
need for more reliable and abundant bone substitutes to
replace or repair bone defects in clinics.
In the past decades, with the development of materials
science and biology, a series of bone graft substitutes have
been produced. Indeed, there are currently over 100 approved
bone replacement materials in Germany alone [12], through
which three different generations have been evolved [13]: the
Biomaterials and Bone Tissue Engineering
Wenfeng Xu, Xiaoling Liao﹡, Bo Li and Taifu Li
B
224
first-generation “bioinert” materials; the second-generation
“bioactive and biodegradable” materials; and the
third-generation “cell- and gene-activating” materials
(designed to stimulate specific cellular responses at the
molecular level with the aim of developing materials that,
once implanted, will stimulate the body to heal by itself).
These three generations of materials are shown in Table 1 as
follows [14]
During the 1960s and 1970s, the first-generation
materials were developed with the simple goal of achieving
“a suitable combination of physical properties to match those
of the replaced tissue with a minimal toxic response in the
host” [1]. In 1980, around 2 to 3 million prosthetic parts were
implanted in patients in the United States, which had
enhanced these patients’ life quality for 5 to 25 years with
such “inert” biomaterials [3]. In the mid-1980s, the second
generation “bioactive” materials were developed and applied
in clinics for orthopedic and dental applications. By the
1990s, bioactive composites including hydroxyapitite
particles have become important in the repair and
replacement of bones [1]-[4]. Although some of the above
first and second generation substitutes have been successfully
applied to replace or repair bone defects in clinics, they are
limited in part due to the fact that they are man-made, and
thus cannot respond to physiological loads change or
biochemical stimuli. For most first and second generation
biomaterials, stress shielding effect results from the mismatch
of the mechanical properties between the host bone and the
implant. In addition, the surface properties inhibiting the new
tissue regeneration which can lead to the loosening of implant
from host bones. This became the main reason of orthopedic
implant failure, and also a third to half of prostheses failed
within 10 to 25 years [4]. New strategy is hence needed to
further improve the repair and regeneration of bone tissues.
During the first decade of the 21st century, the new third
generation, “cell- and gene-activating” biomaterials (also
called bone tissue engineering materials), have been tailored
into the extracellular matrix (ECM) scaffolds. This allows the
bone progenitor cells to seed on scaffolds for proliferation
and differentiation in vitro, thus better mimicking naturally
surrounding tissue before being implanted into the patients
[3]. Bone tissue engineering has gained increasing
recognition to treat bone defect since it can stimulate new
bone tissue regeneration in the host by inducing bone cells
adhesion and proliferation. This provides a more effective
approach than the traditional methods (Laurencin, Ambrosio
et al. 1999; Hench and Thompson 2010). This hybrid
construct is a typical third-generation “cell- and
gene-activating” material [4-6]. After a minimally invasive
surgery to insert the hybrid construct to the disease or injury
site, the self-healing process occurs by stimulating the
specific response of cells at a molecular level, activating
specific gene expression to regulates regeneration, and
gradually replacing the missing bone with newly formed
tissue [15]. Thus, the new bone repair therapy can be simply
defined as the ‘science of persuading the body to heal by its
intrinsic repair mechanisms’ [15]-[17].
To date, one of the most advanced bone tissue
engineering methods is to transplant hybrid cell-material
constructs into patients, which incorporate cells, a 3D porous
scaffold, and bioactive factors as an integrated bone graft
substitute. Recently, many new biomaterials scaffold
appeared, specially, the activated biomaterials particles and
3D porous activated biomaterials scaffold.
For example, Xu [18]-[20] preparated the porous Carbon
fiber/Polylactic acid/Chitosan (CF/PLA/CS) composites
scaffold by using process of solvent blending and
freeze-drying technique (Fig.1).The results shows that the
sizes of pores in the composites were from 20 μm to 500 μm,
the pores distributed well, and connected each other.
Abstract—during the last decades, bone tissue repair and
regeneration have been increasing interest in the clinical
therapy scientific field, and with the development of materials,
biology and tissue engineering, the bone tissue engineering has
been as an efficient method to treat bone defects. This review
summarizes several aspects related to bone tissue engineering
for bone repair and regeneration: the biomaterials in the bone
tissue engineering, the stem cell behavior in bone tissue
engineering, and the development of biomaterials and bone
tissue engineering. We also highlight several latest
advancements in bone tissue engineering. Finally, a brief
summary of the bone tissue engineering challenges in the field
are provided with suggestions for future research directions.
I. INTRODUCTION
ONES are important structural components for the
vertebrates, which is composed of 60% hydroxyapatite,
10% water and 30% collagen proteins. Bones play important
roles to provide mechanical support for locomotion,
protecting vital organs, and regulating the metabolism of
calcium and phosphorus, and so on. All these functions
requires a healthy bone balance system [1]. However,
millions of people in the world suffer from bone defects due
to many reasons, including trauma, tumor, bone diseases,
congenital defects and aging. These defects are increasingly
becoming the major clinical cases.
The biomaterials are indispensable in the bone repair
therapies; recent advances in the bone repair research have
highlighted the cell-material composite of tissue engineering
which provide the unique self-repair capacity to remodel.
Once implanted, the cell-material composite help the body to
heal itself [2].The constructs are seeded with stem cells,
usually derived from the bone marrow, and then different into
the bone cells under the process of proliferation and
Manuscript received Juny 22, 2011. This work was supported in part by
the Chongqing University of Science and Technology under Grant
CK2010B18.
First Author, Wenfeng Xu, was with the Department of Chemical and
Environmental Engineering, Chongqing University of Art and Science,
Chongqing, China, 402160 (corresponding phone: 023-49682200; fax:
023-49682200, e-mail: xwf_228@163.com).
Second Author, Xiaoling Liao﹡, was the paper’s corresponding author
with the Institute of Biomaterials and Living cell Imaging, Chongqing
University of Science and Technology, Chongqing, China,
401331(corresponding phone: 023-65023701, fax: 023-65023701; e-mail:
zxc_228@163.com).
Third Author, Bo Li, was with the Institute of Biomaterials and Living
cell Imaging, Chongqing University of Science and Technology, Chongqing,
China,401331(corresponding phone: 023-65023701, fax: 023-65023701;
e-mail: leewave@126.com).
Fourth Author, was with the Institute of Biomaterials and Living cell
Imaging, Chongqing University of Science and Technology, Chongqing,
China,400050(corresponding phone: 023-65023701, fax: 023-65023701).
differentiation in vitro conditions [3]. The new bone tissue
regeneration is charged by these bone cells under tightly
controlled microenvironment including chemical and
mechanical stimuli, for example, the surface chemical and
physical characteristics of the scaffold, the shear stress of the
humour, and so on [4].
In this paper, we summarize and provide an overview of
published studies on the biomaterials in the bone tissue
engineering, the stem cell behavior in bone tissue
engineering. We also highlight several latest advancements in
bone tissue engineering. Finally, a brief summary of the bone
tissue engineering challenges in the field are provided with
suggestions for future research directions.
II. BIOMATERIALS FOR BONE TISSUE ENGINEERING
Although slight bone fractures can be easily self-repaired,
serious bone defects or diseases (i.e., comminuted fracture,
osteoporotic and cartilaginous tissues) are difficult to
regenerate and remodel by itself-healing [5]. In this case,
surgery is often required to implant bone graft or artificial
materials at the site of injury or disease [6]. According to
statistics, there are more than 12 million operations requiring
bone substitutes in our world alone each year and the demand
continues to rise drastically. For example, there will be a
174% increase for first-time total hip replacements, and a
673% increase for first-time total knee replacements by the
year 2030 (AAOS 2006c). Such statistics does not include the
steadily growing number of revision surgeries resulted from
the average lifespan (only 10 to 15 years) of an orthopedic
implant [7]. It is clear that the bone implants are becoming a
highly demanded resource for the clinical needs, which will
have significant socio-economic benefits over worldwide.
The traditional bone repair procedure involves the use of
autografts (from the patient iliac crest) and allografts (from
the cadaver bone) [8]. Autograft is still considered as the gold
standard in the reconstruction of bone defects until now,
because it has the structural stability and natural osteogenic
ability [9]. Although the autograft and allograft procedures
have been fairly successful, there are serious limitations such
as limited supply of donor bone tissue, unpredictable
rejection characteristics, infection and donor site morbidity
[10]. Particularly, large bone defects are a major clinical
problem since autologous bone grafts are not available in up
to 40% of these patients [11]. Therefore, there is a pressing
need for more reliable and abundant bone substitutes to
replace or repair bone defects in clinics.
In the past decades, with the development of materials
science and biology, a series of bone graft substitutes have
been produced. Indeed, there are currently over 100 approved
bone replacement materials in Germany alone [12], through
which three different generations have been evolved [13]: the
Biomaterials and Bone Tissue Engineering
Wenfeng Xu, Xiaoling Liao﹡, Bo Li and Taifu Li
B
224
first-generation “bioinert” materials; the second-generation
“bioactive and biodegradable” materials; and the
third-generation “cell- and gene-activating” materials
(designed to stimulate specific cellular responses at the
molecular level with the aim of developing materials that,
once implanted, will stimulate the body to heal by itself).
These three generations of materials are shown in Table 1 as
follows [14]
During the 1960s and 1970s, the first-generation
materials were developed with the simple goal of achieving
“a suitable combination of physical properties to match those
of the replaced tissue with a minimal toxic response in the
host” [1]. In 1980, around 2 to 3 million prosthetic parts were
implanted in patients in the United States, which had
enhanced these patients’ life quality for 5 to 25 years with
such “inert” biomaterials [3]. In the mid-1980s, the second
generation “bioactive” materials were developed and applied
in clinics for orthopedic and dental applications. By the
1990s, bioactive composites including hydroxyapitite
particles have become important in the repair and
replacement of bones [1]-[4]. Although some of the above
first and second generation substitutes have been successfully
applied to replace or repair bone defects in clinics, they are
limited in part due to the fact that they are man-made, and
thus cannot respond to physiological loads change or
biochemical stimuli. For most first and second generation
biomaterials, stress shielding effect results from the mismatch
of the mechanical properties between the host bone and the
implant. In addition, the surface properties inhibiting the new
tissue regeneration which can lead to the loosening of implant
from host bones. This became the main reason of orthopedic
implant failure, and also a third to half of prostheses failed
within 10 to 25 years [4]. New strategy is hence needed to
further improve the repair and regeneration of bone tissues.
During the first decade of the 21st century, the new third
generation, “cell- and gene-activating” biomaterials (also
called bone tissue engineering materials), have been tailored
into the extracellular matrix (ECM) scaffolds. This allows the
bone progenitor cells to seed on scaffolds for proliferation
and differentiation in vitro, thus better mimicking naturally
surrounding tissue before being implanted into the patients
[3]. Bone tissue engineering has gained increasing
recognition to treat bone defect since it can stimulate new
bone tissue regeneration in the host by inducing bone cells
adhesion and proliferation. This provides a more effective
approach than the traditional methods (Laurencin, Ambrosio
et al. 1999; Hench and Thompson 2010). This hybrid
construct is a typical third-generation “cell- and
gene-activating” material [4-6]. After a minimally invasive
surgery to insert the hybrid construct to the disease or injury
site, the self-healing process occurs by stimulating the
specific response of cells at a molecular level, activating
specific gene expression to regulates regeneration, and
gradually replacing the missing bone with newly formed
tissue [15]. Thus, the new bone repair therapy can be simply
defined as the ‘science of persuading the body to heal by its
intrinsic repair mechanisms’ [15]-[17].
To date, one of the most advanced bone tissue
engineering methods is to transplant hybrid cell-material
constructs into patients, which incorporate cells, a 3D porous
scaffold, and bioactive factors as an integrated bone graft
substitute. Recently, many new biomaterials scaffold
appeared, specially, the activated biomaterials particles and
3D porous activated biomaterials scaffold.
For example, Xu [18]-[20] preparated the porous Carbon
fiber/Polylactic acid/Chitosan (CF/PLA/CS) composites
scaffold by using process of solvent blending and
freeze-drying technique (Fig.1).The results shows that the
sizes of pores in the composites were from 20 μm to 500 μm,
the pores distributed well, and connected each other.
การแปล กรุณารอสักครู่..