close

Вход

Забыли?

вход по аккаунту

?

bk-2017-1253.ch008

код для вставкиСкачать
Chapter 8
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
Construction of Bio-Inspired Composites for
Bone Tissue Repair
Junchao Wei,*,1 Lina Wang,1,2 Lan Liao,3 Jiaolong Wang,3 Yu Han,4
and Jianxun Ding*,4
1College
of Chemistry, Nanchang University, Nanchang 330031, P. R. China
of Science, Nanchang Institute of Technology, Nanchang 330029,
P. R. China
3Department of Prosthodontics, Affiliated Stomatological Hospital of
Nanchang University, Nanchang 330006, P. R. China
4Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied
Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
*E-mail: weijunchao@ncu.edu.cn (J. Wei); jxding@ciac.ac.cn (J. Ding)
2College
Materials with excellent mechanical properties and biofunctions
are key points of bone tissue repair. With the increase of
knowledge about bone tissue structure and the development of
nanotechnology, tough materials have been designed to mimic
the structure of bone. Based on the structure of bone and nacre,
we briefly introduced the factors affecting the mechanical
properties of composites and also introduced the most widely
used techniques, such as, electrospinning, phase separation,
and three-dimensional (3D) printing method, to acquire porous
scaffolds. In addition, the biofunctionalization of scaffolds was
also introduced in this chapter.
1. Introduction
Due to various diseases, accidents and aging of population, bone defect has
been a common problem. Autologous bone graft is the gold standard for treating
bone defect, however, it also brings a lot of side effects to patients. Although
Allograft and Xenograft has brought some promise, sometimes donors’ shortage
and immune response limit their application, and thus much work has been
carried out to design alternative bone graft materials, which may be composed of
© 2017 American Chemical Society
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
polymers, metals, and ceramics. Tissue engineering, which applies the principles
of engineering and life sciences towards the development of biological substitutes
to restore, maintain or improve the tissue functions (1, 2), has been an exciting
and promising method to repair the bone defect. During the process of tissue
engineering, the tissue engineering scaffold is a key factor to affect the functional
reconstruction of tissues. The general requirement for a tissue engineering
scaffold is that the scaffold materials should not only fill the defect area, but also
supply both structure and mechanical support (3), even bio-functions to realize
the regeneration of bone (4). And thus, much attention has been paid to the
materials used in bone tissue engineering (5, 6).
The materials of bone tissue engineering scaffolds or bone tissue regenerative
composites should have proper mechanical properties to support the growth of
bone tissue, furthermore, as for the load-bearing place, the mechanical properties
are the key factors, and this point is very important for bone substitutes or bone
fixation devices. Secondly, the porous structure should also be realized for the
supplement of the ample space to support the growth of new tissues. Thirdly,
enough biofunctions such as biocompatibility, bioactivity, bone conductivity
and bone inductivity are also critical factors for materials used in bone tissue
engineering. So far, various methods have been developed to fabricate polymer
composites used in bone tissue repair. Bio-inspired idea has been widely used
to design new materials or scaffolds that can mimic the functions of native bone
tissue. However, before designing ideal bio-inspired composites, it is vital to
understand the structure of native tissue and also it is much helpful to understand
the interactions between polymers, nanofillers, and cells.
In this chapter, we firstly give a brief introduction of bone structure and the
reason why it is tough and strong, and then materials used in bone tissue repair
was introduced, finally, methods about how to construct bone-inspired composites
were introduced. This short review may give an idea about how to construct strong
and tough materials used in bone tissue engineering, and also give some suggestion
on how to design biofunctionalized scaffolds.
2. Materials for Bone Tissue Repair
2.1. Natural Strong and Tough Materials—Bone & Nacre
Bone is mainly composed of collagen (mostly type I) and hydroxyapatite
(Ca10(PO4)6(OH)2, HA). Both the HA and collagen consists about 95% weight
of the total bone and formed a tough, strong and low weight materials. Collagen
is a kind of natural polymer, its mechanical strength is very low, while HA is a
kind of inorganic bioceramic, its mechanical properties is poor, and much brittle.
However, an interesting thing is that the natural bone is typically strong and tough,
due to the hierarchical structure of HA and collagen, and especially that the HA and
collagen arranged in an order way. Briefly, the HA nanoplates are mostly arranged
along its c-axis and arranged parallel to the collagen fibrils, the arrangement repeat
periodically (Figure 1).
154
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
Figure 1. Hierarchical structure of Bone. Reproduced with permission from ref.
(7). Copyright 2014, Nature publishing group.
The scheme of bone’s resistance to external force is based on its multiple
deformation scales, ranging from nanoscale protein to microscale physiological
structure (7, 8). As for the cortical bone, the origins of its fracture resistance
ability rise from both intrinsic mechanisms that promote ductility and extrinsic
mechanisms that act to shield the growing cracks (8). The intrinsic ductility origins
from the smallest length scales, which is mainly from the molecular uncoiling of
mineralized collagen. Most importantly, when the load is added to the bone, the
stress may transfer between the HA plates and the collagen fibrils, when the stress
is too high, fibrillar sliding may happens, which will make the materials tough to
resist to the tension. Besides, many other factors contribute to the bones, such as
the collagen fibers structure, the phase interaction between HA and collagen, the
intermolecular crosslinking, these factors realize the increased strength of bone.
These factors make it possible to dissipate energy. So, in order to design strong
composites, basic requirements are: realizing the ordered arrangement of fillers,
and enhancing the phase compatibility between fillers and polymer matrix.
Nacre is another kind of strong materials. It is a brick-and-mortar structure
consisting of 95% vol. layered aragonite (CaCO3) plates and a thin layer of protein
molecules (Figure 2). Generally, the mechanical properties of both CaCO3 and
protein molecules are very poor. However, the mechanical toughness of nacre is
three orders of magnitude higher than that of CaCO3. The fracture toughness of
CaCO3 is 0.25 Mp·m1/2, while that of nacre is about 10 Mpa·M1/2, nearly 40 times
that of CaCO3 (9). The mineral aragonite is brittle, and it provides the strength of
nacre. Due to the existence of protein chains (Figure 2a), it is possible for nacre
to realize elastic deformation when external load added. The organic molecules
work as glue to connect with the plate aragonites and realize the stress distribution,
so the nacre shows toughness (Figure 2b).
155
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
Figure 2. Hierarchical structure of nacre. Structure illusion of nanoparticle glued
by protein chains (a), the schemes of its toughness (b) and the brick-and-mortar
structure (c). Reproduced with permission from ref. (7). Copyright 2014, Nature
publishing group.
During recent years, much work has been carried out to prepare nacre or bonelike bioinspired materials. Great progresses have been carried out, most of which
are focused on the structure-properties characteristic. The unique structure of
bone is not only the arrangement of compositions, but also its complex formation
process, in which cells function and involvement place an important role. The
exact understanding of the biomineralization process and structure has contributed
a lot to the design of polymer composites, although much more things need to be
deciphered clearly. Nowadays, although it is difficult to prepare materials that
can completely mimic the structure of bone or nacre, bioninspired idea has been
used to prepare materials from different points, such mechanical properties, porous
structure and biofunctions, which may realize their further application in bone
regeneration.
2.2. Materials Used for Bone Tissue Repair
There are three kinds of materials used in bone tissue repair: metals, ceramics
and polymers (3). They can be used in different parts due to their properties.
Metals, such as titanium alloy and stainless alloy which are biocompatible and
have good mechanical properties, have been used as bone plates or bone screws,
however, this kind of materials always need second operation. Ceramics are most
inorganic materials exist in bioactive glass, HA, tricalcium phosphate (TCP) and
so on, these materials with bone conductivity or bone inductivity are the most
widely investigated inorganic materials, however, these materials are brittle and
can not be used in load bearing parts.
Polymers with good mechanical properties and excellent biocompatibilities
may satisfy the requirements of tissue regeneration, and have been widely used in
tissue engineering. According to the source of polymers, they can be classified as
natural and synthetic polymers. Generally, both degradable and nondegradable
polymers can be used in bone tissue repair. For example, ultra-high molecular
156
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
weight polyethylene and polyether ether ketone (PEEK) have been used as bone
substitute or artificial kneel, however, when tissue engineering is considered,
biodegradable polymers show much more potential, such as collagen, gelatin,
poly(L-lactide) (PLLA), poly(lactide-co-glycolide) (PLGA) and so on, have
been widely used. However, pure polymers can only mimic part functions of
native tissues, they still lack of enough biofunctions to induce bone formation,
or biomechanical properties to satisfy bone loading requirements, so polymer
composites, especially polymers complexed with inorganic bioceramics have been
widely designed. An ideal polymer composite may have hierarchical structure
and possess the advantages of different composites, realizing a synergistic effect
to put forward the applications in bone repair.
Up to now, various polymer composites have been used in bone
tissue repair field, such as polymer-polymer blends and polymer-inorganic
nanocomposites. The most widely investigated bioceramic/polymer composites
are hydroxyapatite/polymer composites. Collage, gelatin, PLLA, PLGA and
their HA composites have been widely investigated or reviewed (10). Besides,
multicomponent composites contains more than two kinds of polymers or two
kinds of inorganic component are also well investigated due to their combination
of multi-advantages of different composites and show much better synergistic
effects. Although much progress has been achieved, there still need a long way
to prepare ideal composites which can mimic the properties of natural tissue and
realize the rapid bone substitute or rebuilt of bone tissue.
3. How To Mimic the Properties of Bone
During the bone repair process, five special targets should be considered,
osteogenesis, vascularization, growth factors, mechanical environment and
osteoconductive scaffolds (3). To realize successful bone regeneration, at least
three of the targets should be involved. Thus, it is vital to design materials with
proper mechanical properties, especially for load-bearing parts. The excellent
properties are inevitable, besides, the materials should also have a proper structure
and bioproperties to support the growth of new tissues.
3.1. Construction of Composites with Excellent Mechanical Properties
Bone tissue has excellent mechanical properties, thus many efforts have been
focused on preparing bone inspired composites, for one purpose to obtain strong
and light weight materials, and another purpose is to prepare bone regenerative
materials or related medical devices, especially for load bearing bone repair, the
mechanical properties are always the vital factors.
Up to now, plenty polymer composites have been designed, however, mostly,
the mechanical properties are far from their theoretical value. A critical challenge
is to transfer the excellent mechanical properties from nanoscale to macroscale
(11). As for filler-reinforced composites, the obtained properties are always
far from their ideal results. The key problem is that they could not realize the
homogeneous dipsersion of nanofillers and easily control their arrangement.
157
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
Another factor is that the phase interaction between the fillers and polymer matrix
are not as strong as the natural bone composition (12).
Nicholas Kotov’s research demonstrated that it is possible to produce
composites with properties that can compare with the theoretical values by tuning
the spatial and orientation of nanofillers (11). They used a bottom up method called
layer-by-layer assembly to prepare a kind of poly(vinyl alcohol)/Montmorillonite
(PVA/MTM) composites. With the LBL method, an interlayer structure was
formed which can mimic the structure of nacre, due to the controlled structure
organization, the clay platelets in polymer matrix arranged orderly, due to much
hydroxyl groups of PVA chains and SiO4 groups in MTM, the phase interaction
between PVA and MTM are strong. Besides, when the film was crosslinked
with GA, the interaction will be much stronger, and the mechanical properties
can arrive to its theoretical value. The final tensile strength of the crosslinked
PVA/MTM was 400±40Mpa, and the modulus was 106±11Gpa.
By tuning the arrangement of nanofillers, various strong bio-inspired
composites have been designed. Recently, Robert O Ritchie has reported a kind
of hydroxyapatite/poly(methyl methacryalate) (HA/PMMA) composites with
layered structure (preparation scheme is shown in Figure 3) (13), which can
mimic the nacre structure and work as a kind of tissue engineering scaffolds.
The strength, elastic stiffness and work of fracture were 100 Mpa, 20 Gpa and
2075 J·m-2, respectively. These results are nearly two orders of magnitude than
monolithic HA.
Figure 3. Schematic illustration of fabrication of HA/PMMA composite with
nacre-mimetic structure. Reproduced with permission from ref (13). Copyright
2015, John wiley and Sons.
158
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
Another important factor to enhance the mechanical properties of polymer
composites is to improve the phase compatibility of nanofillers and polymer
matrix. Up to now, many works have been reported to tune the surface properties
of nanoparticles by grafting polymer chains on the surface of nanofillers (14–18).
As for bone tissue regenerative materials, bioceramics such as hydroxyapatite,
bioactive glass are most important to endow polymers with bone conductivity
or bone inductivity. However, pure bioceramic particles are brittle and their
phase interaction with polymers are always too weak, and thus polymer grafted
bioceramics have been prepared. For example, Chen’s group have used
ring opening polymerization method to graft polymers on the surface of HA
(19–21), PLLA was grafted on the surface of HA and the tensile strength of
PLLA-g-HA/PLLA (75 Mpa) was much higher than that of pure HA/PLLA
composite (less than 60 Mpa). Besides, PLLA-g-HA can also be used to prepare
porous scaffold and showed excellent osteogenesis properties (22). Wei used
poly(benzly-l-glutamate) to modify the surface of HA not only change its
biocompatibility, but also increase its phase compatibility with Polymer matrix,
and the results showed that only 0.3% content can make the mechanical properties
increased a lot (18). Besides, Wei’s group also used PBLG to modify the surface
of SiO2@GO hybrid and then prepared its PLLA composites, the results showed
that the tensile strength of PLLA composites can arrive to 88.9 Mpa, much higher
than that of pure PLLA, PLLA/GO or PLLA/SiO2 (23).
3.2. Construction of Porous Scaffolds for Bone Tissue Repair
The natural bone is porous structure, while tissue engineering scaffolds also
need porous structure to support the growth of tissues. Many methods, such as
electrospinning, phase separation and 3-D printing have been used to prepare
porous structure scaffolds to realize the regeneration of bone tissue. Here, we will
give a brief introduction about these methods.
3.2.1. Electrospinning
Electrospinning method has been widely used to construct fibrous porous
scaffold to mimic the fibrillar architecture of extracellular matrix (ECM). These
fibrous biomimetic scaffolds can supply microenvironment for the regenerative
of bone tissue. The basic progress of electrospinning contains three parts (Figure
4a). Firstly, polymer solutions were extruded from a conductive spinneret, and
then voltage was applied between the spinneret and grounded collector. When
the electric potential in the polymer solution overcomes the surface tension of
polymer solution droplet, the droplet will eject to the collector, during this period,
the solvent will evaporate, and polymer fibers will be collected on the collector.
159
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
Figure 4. Schemes of basic electrospinning process (a) and fibers with different
orientation, random fiber (b), parallel fiber (c), crossed fiber (d), patterned fiber
net (e), 3D fibrous stack (f), wavy fiber (g), helical fiber (h), and twisted fibers (i).
Reproduced with permission from ref. (26). Copyright 2014, Elsevier.
The electrospinning fibers have showed potential applications in tissue
engineering, the morphologies of electrospun fibers, such as fiber size, porosity,
fiber orientation may affect the attached cells behaviors, thus many efforts have
been worked to tune the structure or morphologies of fibers (24). Firstly, the
polymer concentration is a key factor, it has to exceed a critical concentration so
that enough polymer chains entangle within the polymer solution, then polymer
fibers can be formed via electrospinning. Otherwise, dilute polymer solutions
will spray into beads or uniform polymer fibers with much more beads aggregate.
It is also important to choose polymers with proper molecular weight. If the
molecular weight is too low, the polymer chains can not entangle well and it
is difficult to form fibers. If the molecular weight is too high, the polymer
entangles a lot and increases the solution viscosity, which means the surface
tension of droplet is much higher, and thus it is also difficult to form fibers, unless
high pressure voltage was used. So it is vital importance to tune the polymer
solution, some times other additive, such as surfactant or amphiphilic molecules
should be added. Besides, the solvent can also be a critical factor to affect the
solution viscosity, proper solvent, sometimes mix solution is a prerequisite to
obtain designed fibers (25). In addition, with different kinds of jet or needle, and
different kinds of collectors can realize different morphologies electrospun fibers,
160
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
fibers with different morphologies or arrangement such as random or orientation
aligned fibers can be prepared via different technologies (26).
Electrospinning as an important method to prepare new tissue engineering is
not only used to prepare polymer materials, up to now, various polymer blend or
polymer-inorganic composites have been prepared, Such as PLA/PCL (27), PLLA
grafted hydroxyapatite/PLLA (28), gelatine/chitoasan/hydroxyapatite/graphene
oxide. With the increasing requirements for tissue engineering, various functional
molecules (growth factor, proteins) and drugs can be loaded with fibers and enrich
the properties of tissue engineering scaffolds (29, 30) (see part 3.3).
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
3.2.2. Phase Separation
Phase separation is a simple method to prepare porous or fibrous structure
that can mimic the native structure of ECM and has been widely used in tissue
engineering scaffolds. The basic principle of phase separation is based on the
thermally unstability of polymer solutions and tend to separate into two or more
phases under certain conditions (31–33), briefly, either exposuring the polymer
solution to a immiscible solution or cooling down to a certain temperature, phase
separation would happen and form a polymer-rich phase and a polymer-poor
phase. The basic procedure of phase separation includes polymer dissolution,
phase separation and gelation, solvent extraction, freezing and freeze drying (31).
By tuning the parameters of phase separation, porous scaffolds with different
pore sizes and shapes can be obtained (34), for example, by tuning the temperature
below or above the polymer solutions, both closed and open pores can be obtained,
respectively; Under lower temperature, the solvent can crystallize quickly and the
crystal size will be smaller, when the solvent crystal was removed, the scaffolds,
with smaller pores will be obtained, otherwise, scaffolds with large pores can
be formed. even the cooling rate and freezing temperature may have also vital
affection on the pore structure (35). For example, when frozen at -80 °C and 190
°C, PLLA scaffolds with different pore sizes 47±8 and 22±4μm were prepared
(36), many other kinds of scaffolds, such as chitosan, PLLA/chitosan have also
been prepared by phase separation method (37).
Sometimes it is difficult to realize precise control of the microstructure, some
modified methods or combination of phase separation methods and other methods,
such as solvent casting, porogen leaching and supercritical method have been
used (38), polymer solution can be cast around salt sugar and other porogen. By
tunning the size of porogen agents, scaffolds with different porous structures can
be obtained, and thus it is vital important in tissue engineering, due to that the pore
size has an important effect on the cell behavior and bone formation (39).
3.2.3. 3D Printing
Although various methods such as elecrospinning, phase separation solvent
casting, and salt leaching and many other methods have been designed to prepare
porous scaffolds, it is still a challenge to precise control the hierarchical structure
161
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
such as pore size, shape and pore interconnectivity. Inspired by the complex
structure of biological materials, especially some native tissue structure such
as bone or nacre, 3D printing has been used to fabricate various scaffolds with
intricate microstructure (40, 41). 3D printing applies additive manufacturing
approaches, combine computer assisted design (CAD) software and printing
machine together to prepare products by a layer-by-layer method, and the basic
procedure has been introduced in many references (42, 43).
The basic characteristics of 3D printing can be described as follows (44): A)
supply of building blocks or raw materials in a continuous or stepwise method.
B) A programme that contains the structure information should be supplied to
determine the assembly of materials. C) Mechanisms or equipments that can fulfill
the programme and control the assembly of building blocks. D) A consolidation
step to fix the deposited materials and make the printed structure as designed.
Up to now, various technologies, such as deposition modeling,
stereolithography, ink-jet printing have been used to prepare tissue engineering
scaffolds and can easily realize on-demand fabrication of customized products
with precise structures (44, 45). For bone tissue engineering, 3D printing is
very convenient to construct scaffolds with desired structure. Meantime, with
the development of 3D technology, various materials, such as ceramic, metallic,
polymers and polymer composites can be used for 3D print (46, 47). Cho used
sterolithography method and prepared three-dimensional (3D) porous scaffolds
of poly(propylene fumarate)/diethyl fumarate (PPF/DEF) (48), which have
sufficient mechanical stability and are non-toxic. After post-modification, the
scaffold can enhance the adhesion and proliferiation of MC3T3-E1 preosteoblast
cells, showing potential application in bone tissue repair. Polyester, such as
PLA, PCL, PLGA have been widely used in bone tissue engineering, when
combined with 3D technology, various scaffolds have been prepared with these
biodegradable polymers (49). Inorganic materials, such as HA, α-TCP, β-TCP
and bioactive glass have also been used as 3D printing materials to build bone
tissue engineering scaffolds (50). In order to combine the bone inductivity
of bioceramics and the biodegradability of polymers, bioceramics, HA, TCP,
bioactive glass have been used as fillers to prepare polymer composites used for
bone tissue engineering. For examples, PLLA/HA, chitosan/HA, collagen/HA
and alginate/bioactive glass have been prepared with 3-D printing (51–53).
Via 3-d printing method, scaffolds which can mimic the structure of native
bone tissue can be prepared easily; however, the mechanical properties of
porous scaffolds are still challenges. The porous structure always results in low
mechanical properties, and always used in non-load bearing place. However, by
tuning the delicate printing method, it is a good method to realize the requirements
of complicated structures. For example, PolyJet 3-D printing method based
on ink jet technology can realize deposition of multi-materials, which enables
the possibility to prepare both strong and tough materials. This method would
be much useful to prepare polymer composites that can mimic the bone (44,
54). Buelher had used multi-material 3D printing to print composites with
bone-inspired topologies that exhibit superior fractural mechanical properties,
and the computational model predictions of the fracture behaviors and trends
in mechanical properties are in accordant with the experimental results,
162
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
demonstrating that it is possible to design composite materials and then use
3-D printing to synthesize the desired materials with expected mechanical
performance (54).
3-D printing will have much more promising perspective in tissue
engineering. However, many critic requirements, such as specific technical,
material and cellar aspects of the printing process will bring more challenges
(43). The increasing resolution requirements may make 3-D printed products
mimic the tissue structure more exactly. The ideal materials should not only be
biocompatible, but also can be easily manipulated by the printing technology
to acquire complex 3-D structure and maintain its bioproperties. The cells used
should be easily available, and can reproduce all the functions of tissue or organ
system (43), so multidiscipline should forged together to meet the challenges and
thus further improve the application of 3-D printing in tissue engineering.
3.3. Composites with Special Biofunctions
Although most biocompatible polymers or polymer composites can be made
into scaffolds that can mimic the structure of native tissue, but it is difficult to
mimic the biofunctions. The cell functions and growth factors play critical roles
in the process of tissue regeneration, so various methods have been used to prepare
composites with special biofunctions.
Firstly, the native biomacromolecues or polymers found in the ECM can be
used as ideal scaffolds to mimic the biofucntions. Collagen, the most organic
content of bone, has been used for a long time. It is not only used alone, but
also blended with various polymers or inorganic particles. Other materials, such
as hydroxyapatite, the inorganic component of bone, have also been widely used in
tissue engineering or bone repair, due to its bone conductivity or bone inductivity
properties.
In order to further improve the biofunctions, increasing works have been
focused on the combination of scaffolds and biomacromolecules, such as protein
or growth factors (BMP, IGF). The growth factors can control osteogenesis,
bone tissue regeneration and ECM formation via recruiting and differentiation
osteoprogenitor cells to specific lineages (55). So it is critical to incorporate
protein or growth factors in the tissue engineering scaffolds. Generally, there are
two kinds of method to prepare biomacromolecules contained scaffolds. One
method is pre-treat method, which means that biomolecules were added into
the scaffolds while the preparation process. The other method can be called
post-treatment method, which means the biomacromolecules were adsorbed or
anchored on the scaffolds by physical or chemical interactions. For example,
biomolecules contained electrospinning scaffolds can be prepared via different
blend electrospinning, coaxial electrospinning and covalent immobilization
methods (56), and these methods can realize the functional molecules be adsorbed
or covalently anchored on the surface of fibers or encapsulated within the fibers.
The configurations of biomolecules have key effects on their signal
transduction activity, and thus it is critical to keep the structure of growth factors.
Mussel-inspired method with 3,4-dihydroxyphenethylamine (DOPA) contained
peptide has been widely used, recently Ito’s group designed a method to prepare
163
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
DOPA containing insulin-like growth factor-1(IGF-1) and anchor the IGF-1 on the
surface titanium (Figure 5). This method can be used to prepare novel cell-growth
enhancing materials and thus have much potential in tissue engineering (57).
Zhang’s group also used the mussel-inspired method and immobilized collagen
mimetic peptide and osteogenic growth peptide on the surface of L-lactic
acid oligomer modified hydroxyapatite/Poly(lactide-co-glycoclide) composite
film (58). The results demonstrated that it is a good method to immobilize
biomacromolecues on the surface of implants with bioinspired method and realize
their enhanced osteointegration of bone implants.
Figure 5. Preparation of DOPA contained IGF-1 derivatives and its
immobilization on the surface of titanium. Reproduced with permission from ref
(57). Copyright 2016, John wiley and Sons.
To encapsulate special cells in the scaffolds is also a good method to improve
the biofunction of scaffolds, for example bio-printing has been designed to prepare
cells contained scaffolds (43), and it can combine the biocompatible materials,
cells and other components into a functional living tissue and thus will have much
more applications.
4. Perspective
In this chapter, we briefly introduce the structure of bone and how to
construct the bio-inspired composites used in the field of bone tissue repair.
Due to the requirements of bone tissue regenerative, tough materials with
excellent mechanical properties and scaffolds with porous structure and special
biomolecules are needed in bone tissue repair. Although many progresses
164
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
have been achieved, there still need a long way to prepare ideal scaffolds or
substitutes that can real mimic the bone structure or properties. However, by
further understanding the structure of native bone and the interactions between
materials and tissues, new hints maybe brought out to the materials design, and
the challenges will be overcame via the combination of materials, engineering,
biology, medicine, and others. To our opinion, in the next few years, more
interests will be placed on the design of new functional materials with special
biofunctions, or prepared new functional polymer composites, which may be used
for bone implant medical devices or manufactured into scaffolds with desired
structure. As a basic requirement, how to realize enhancements of both toughness
and strength, and make the mechanical properties satisfied for bone tissue will
still be an interesting point. New preparation method or modification method will
be continuously investigated to realize the multi-functions of tissue engineering
scaffolds, such as how to keep the long term stability of growth factors or realize
its controlled release in the scaffolds, and how to control the scaffold structure
exactly, especially in the nanoscale level. Furthermore, reproducing all the
functions of living tissue or organs is still a huge challenge, by mimicking the
structure of bone tissue, the structures of scaffolds and their affection on the
biofunctions will be an interesting topic, scaffolds loaded with living cells will
arouse more interest to mimic the biofunction of living tissue, and have much
more potential application in regenerative medicine.
Acknowledgments
This work was financially supported by the National Natural Science
Foundation of China (Nos. 51463013, 51663017, 81660444, and 51673187),
the Natural Science Foundation of Jiangxi Province of China (No.
20151BAB206011), the Health and Family Planning Commission Science
Foundation of Jiangxi Province of China (No. 20161082), and Natural Science
Foundation of Nanchang Institute of Technology (No. 2012KJ028).
References
1.
2.
3.
4.
5.
6.
7.
8.
Tian, H.; Tang, Z.; Zhuang, X.; Chen, X.; Jing, X. Prog. Polym. Sci. 2012,
37, 237–280.
Langer, R.; Vacanti, J. P. Science 1993, 260, 920–926.
Jahan, K.; Tabrizian, M. Biomater. Sci. 2016, 4, 25–39.
Carrow, J. K.; Gaharwar, A. K. Macromol. Chem. Phys. 2015, 216,
248–264.
Bose, S.; Tarafder, S. Acta Biomater. 2012, 8, 1401–1421.
Pina, S.; Oliveira, J. M.; Reis, R. L. Adv. Mater. 2015, 27, 1143–1169.
Wegst, U. G. K.; Bai, H.; Saiz, E.; Tomsia, A. P.; Ritchie, R. O. Nat. Mater.
2015, 14, 23–26.
Launey, M. E.; Buehler, M. J.; Ritchie, R. O. Annu. Rev. Mater. Res. 2010,
40, 25–53.
165
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
9.
10.
11.
12.
13.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
Barthelat, F.; Tang, H.; Zavattieri, P. D.; Li, C. M.; Espinosa, H. D. J. Mech.
Phys. Solids 2007, 55, 306–337.
Wang, J.; Wang, L.; Zhou, Z.; Lai, H.; Xu, P.; Liao, L.; Wei, J. Polymers
2016, 8, 115.
Podsiadlo, P.; Kaushik, A. K.; Arruda, E. M.; Waas, A. M.; Shim, B. S.;
Xu, J.; Nandivada, H.; Pumplin, B. G.; Lahann, J.; Ramamoorthy, A.;
Kotov, N. A. Science 2007, 318, 80–83.
Bonderer, L. J.; Studart, A. R.; Gauckler, L. J. Science 2008, 319, 1069–1073.
Bai, H.; Walsh, F.; Gludovatz, B.; Delattre, B.; Huang, C.; Chen, Y.;
Tomsia, A. P.; Ritchie, R. O. Adv. Mater. 2016, 28, 50–56.
Li, W.; Xu, Z.; Chen, L.; Shan, M.; Tian, X.; Yang, C.; Lv, H.; Qian, X.
Chem. Eng. J. 2014, 237, 291–299.
Kuila, T.; Bose, S.; Mishra, A. K.; Khanra, P.; Kim, N. H.; Lee, J. H. Prog.
Mater. Sci. 2012, 57, 1061–1105.
Wei, J.; He, P.; Liu, A.; Chen, X.; Wang, X.; Jing, X. Surface Macromol.
Biosci. 2009, 9, 1237–1246.
Wei, J.; Liu, A.; Chen, L.; Zhang, P.; Chen, X.; Jing, X. Macromol. Biosci.
2009, 9, 631–638.
Wei, J.; Dai, Y.; Chen, Y.; Chen, X. Sci. China-Chem. 2011, 54, 431–437.
Hong, Z. K.; Qiu, X. Y.; Sun, J. R.; Deng, M. X.; Chen, X. S.; Jing, X. B.
Polymer 2004, 45, 6699–6706.
Hong, Z. K.; Zhang, P. B.; He, C. L.; Qiu, X. Y.; Liu, A. X.; Chen, L.;
Chen, X. S.; Jing, X. B. Biomaterials 2005, 26, 6296–6304.
Qiu, X. Y.; Hong, Z. K.; Hu, J. L.; Chen, L.; Chen, X. S.; Jing, X. B.
Biomacromolecules 2005, 6, 1193–1199.
Zhang, P.; Hong, Z.; Yu, T.; Chen, X.; Jing, X. Biomaterials 2009, 30, 58–70.
Guo-Wang, P. Y.; Ding, J. X.; Guo, W.; Wu, H. Y.; Wei, J. C.; Dai, Y. F.;
Deng, F. J. RSC Adv. 2016, 6, 5688–5694.
Lin, J.; Wang, X.; Ding, B.; Yu, J.; Sun, G.; Wang, M. Crit. Rev. Solid State
Mater. Sci. 2012, 37, 94–114.
Lin, J.; Ding, B.; Yu, J.; Hsieh, Y. ACS Appl. Mater. Interfaces 2010, 2,
521–528.
Sun, B.; Long, Y. Z.; Zhang, H. D.; Li, M. M.; Duvail, J. L.; Jiang, X. Y.;
Yin, H. L. Prog. Polym. Sci. 2014, 39, 862–890.
Li, H. T.; Qiao, T. K.; Song, P.; Guo, H. L.; Song, X. F.; Zhang, B. C.;
Chen, X. S. J. Biomater. Sci., Polym. Ed. 2015, 26, 420–432.
Wei, J. C.; Guo-Wang, P.; Han, Q.; Ding, J. X.; Chen, X. S. J. Controlled
Release 2015, 213, E62–63.
Place, L. W.; Sekyi, M.; Taussig, J.; Kipper, M. J. Macromol. Biosci. 2016,
16, 371–380.
Braghirolli, D. I.; Steffens, D.; Pranke, P. Drug Discovery Today 2014, 19,
743–753.
Holzwarth, J. M.; Ma, P. X. Biomaterials 2011, 32, 9622–9629.
Ma, P. X. Mater. Today 2004, 7, 30–40.
Ma, P. X. Adv. Drug Delivery Rev. 2008, 60, 184–198.
Akbarzadeh, R.; Yousefi, A.-M. J. Biomed. Mater. Res., Part B 2014, 102,
1304–1315.
166
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Downloaded by GEORGETOWN UNIV on October 26, 2017 | http://pubs.acs.org
Publication Date (Web): October 25, 2017 | doi: 10.1021/bk-2017-1253.ch008
35. Mannella, G. A.; Carfì Pavia, F.; Conoscenti, G.; La Carrubba, V.; Brucato, V.
J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 979–983.
36. Budyanto, L.; Goh, Y. Q.; Ooi, C. P. J. Mater. Sci.: Mater. Med. 2009, 20,
105–111.
37. Salehi, M.; Nosar, M. N.; Amani, A.; Azami, M.; Tavakol, S.; Ghanbari, H.
Int. J. Polym. Mater. Polym. Biomater. 2015, 64, 675–682.
38. Salerno, A.; Fernandez-Gutierrez, M.; Roman del Barrio, J. S.; Domingo, C.
J. Supercrit. Fluids 2015, 97, 238–246.
39. Karageorgiou, V.; Kaplan, D. Biomaterials 2005, 26, 5474–5491.
40. Martin, J. J.; Fiore, B. E.; Erb, R. M. Nat. Commun. 2015, 6, 8641.
41. Le Ferrand, H.; Bouville, F.; Niebel, T. P.; Studart, A. R. Nat. Mater. 2015,
14, 1172–1179.
42. Berman, B. Business Horizons 2012, 55, 155–162.
43. Murphy, S. V.; Atala, A. Nat. Biotechnol. 2014, 32, 773–785.
44. Studart, A. R. Chem. Soc. Rev. 2016, 45, 359–376.
45. He, C. L.; Tang, Z. H.; Tian, H. Y.; Chen, X. S. Acta Polym. Sin. 2013,
722–732.
46. Bose, S.; Vahabzadeh, S.; Bandyopadhyay, A. Mater. Today 2013, 16,
496–504.
47. Guvendiren, M.; Molde, J.; Soares, R. M. D.; Kohn, J. ACS Biomater. Sci.
Eng. 2016, 2, 1679–1693.
48. Shin, J. H.; Lee, J. W.; Jung, J. H.; Cho, D.-W.; Lim, G. J. Mater. Sci. 2011,
46, 5282–5287.
49. Serra, T.; Planell, J. A.; Navarro, M. Acta Biomater. 2013, 9, 5521–5530.
50. Brunello, G.; Sivolella, S.; Meneghello, R.; Ferroni, L.; Gardin, C.;
Piattelli, A.; Zavan, B.; Bressan, E. Biotechnol. Adv. 2016, 34, 740–753.
51. Lin, K.-F.; He, S.; Song, Y.; Wang, C.-M.; Gao, Y.; Li, J.-Q.; Tang, P.;
Wang, Z.; Bi, L.; Pei, G.-X. ACS Appl. Mater. Interfaces 2016, 8,
6905–6916.
52. Li, X.; Cui, R.; Sun, L.; Aifantis, K. E.; Fan, Y.; Feng, Q.; Cui, F.; Watari, F.
Int. J. Polym. Sci. 2014, 829145.
53. Yongxiang, L.; Chengtie, W.; Anja, L.; Michael, G. Biofabrication 2013, 5,
015005.
54. Dimas, L. S.; Bratzel, G. H.; Eylon, I.; Buehler, M. J. Adv. Funct. Mater.
2013, 23, 4629–4638.
55. Bose, S.; Roy, M.; Bandyopadhyay, A. Trends Biotechnol. 2012, 30,
546–554.
56. Ji, W.; Sun, Y.; Yang, F.; van den Beucken, J. J. J. P.; Fan, M.; Chen, Z.;
Jansen, J. A. Pharm. Res. 2011, 28, 1259–1272.
57. Zhang, C.; Miyatake, H.; Wang, Y.; Inaba, T.; Wang, Y.; Zhang, P.; Ito, Y.
Angew. Chem. 2016, 128 (38), 11619–11623.
58. Wang, Z.; Chen, L.; Wang, Y.; Chen, X.; Zhang, P. ACS Appl. Mater.
Interfaces 2016, 8 (40), 26559–26569.
167
Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 2
ACS Symposium Series; American Chemical Society: Washington, DC, 2017.
Документ
Категория
Без категории
Просмотров
8
Размер файла
1 116 Кб
Теги
2017, 1253, ch008
1/--страниц
Пожаловаться на содержимое документа