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Composite Materials for Biomedical Applications: A Review

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Journal of Applied Biomaterials & Biomechanics 2003; 1: 3-18 REVIEW

Composite materials for biomedical


applications: a review
E. SALERNITANO1, C. MIGLIARESI2
1
ENEA - Italian Agency for New Technology, Energy and Environment - Materials and Technologies Division, S. Maria
di Galeria (Roma) - Italy
2
Department of Engineering Materials and Industrial Technologies, University of Trento - Italy

ABSTRACT: The word “composite” refers to the combination, on a macroscopic scale, of two or more materials, different for com-
position, morphology and general physical properties. In many cases, and depending on the constituent properties, composites
can be designed with a view to produce materials with properties tailored to fulfill specific chemical, physical or mechanical re-
quirements. Therefore over the past 40 years the use of composites has progressively increased, and today composite materials
have many different applications, i.e., aeronautic, automotive, naval, and so on.
Consequently many composite biomaterials have recently been studied and tested for medical application. Some of them are cur-
rently commercialized for their advantages over traditional materials. Most human tissues such as bones, tendons, skin, liga-
ments, teeth, etc., are composites, made up of single constituents whose amount, distribution, morphology and properties deter-
mine the final behavior of the resulting tissue or organ. Man-made composites can, to some extent, be used to make prostheses
able to mimic these biological tissues, to match their mechanical behavior and to restore the mechanical functions of the dam-
aged tissue.
Different types of composites that are already in use or are being investigated for various biomedical applications are presented
in this paper. Specific advantages and critical issues of using composite biomaterials are also described (Journal of Applied Bio-
materials & Biomechanics 2003; 1: 3-18)

KEY WORDS: Biomaterial, Composite, Biocompatibility, Bio-functionality, Medical device, Prosthesis, Implant

Received 21/01/03; Revised 04/02/03; Accepted 06/02/03

INTRODUCTION ogy and usually physical properties, made to pro-


duce specific physical, chemical and mechanical
The use of natural or synthetic materials to substi- characteristics. The combination of different ele-
tute or integrate body functions or organs, dam- ments results in a material that maximizes specific
aged by traumatic or pathologic events, to assist tis- properties. The advantage of composites is there-
sue healing or to correct abnormalities, dates far fore that they show the best qualities of their con-
back to the beginning of medicine into ancient civ- stituents, and often exhibit some properties that
ilizations. Therapeutic innovations and the design the single constituents do not have. Moreover, com-
and implementation of complex medical devices posite materials allow a flexible design, since their
permit increased patient survival, significantly im- structure and properties can be optimized and tai-
prove quality of life and contribute to increase life lored to specific applications.
expectancy. Different types of composites, already in use or cur-
The word “composite” refers to a heterogeneous rently investigated for various biomedical applica-
combination, on a macroscopic scale, of two or tions, are presented in this paper. Specific advan-
more materials, differing in composition, morphol- tages and critical issues related to the use of com-

© Società Italiana Biomateriali 1722-6899/003-16$08.00/0


Composite materials for biomedical applications: a review

posite biomaterials versus traditional materials are composites materials in dentistry, mainly polymeric
also pointed out. matrix composites, has considerably grown in the
The remainder of this paper is organized as follows. last years substituting in some cases more tradition-
In Section 1 the cardiovascular applications of com- al materials. Polymer matrix composites are used in
posite materials are described. This is followed by a restorative dentistry to fill cavities, to restore frac-
description of the applications in dentistry (Section tured teeth and to replace missing teeth.
2) and oral and maxillofacial surgery (Section 3). Sec-
tion 4 deals with applications in tissue engineering. In 2.1 Dental restorative materials
the following Section the applications of composite
materials in orthopedics are reported. Concluding re- Composite materials are used in clinical practice to
marks are offered in the last Section. restore anterior and posterior teeth. They have re-
placed polymethylmethacrylate (PMMA) fillings
1. CARDIOVASCULAR APPLICATIONS while amalgams are still used for posterior teeth be-
cause they exhibit better compressive mechanical
Various congenital or acquired lesions related to properties. In most applications, dental composite
the heart and blood vessels lead to severe function- consists of a polymeric acrylic or methacrylic ma-
al diseases requiring surgical treatments. Cardiovas- trix reinforced with ceramic particles. The com-
cular devices are therapeutic supports for heart and mercial formulations of matrices are mainly based
blood vessels. Thrombus formation is the most crit- on bisphenol-A-glycidyldimethacrylate (Bis-GMA);
ical issue for materials placed in contact with blood triethylenglycoldimetachrylate (TEGDMA) is added
and is strongly dependent on surface characteris- to reduce the viscosity.
tics, implantation site, duration, local hemodynam- The most critical aspects for long-term perfor-
ics, etc. The development of a perfect hemocom- mance of dental composites are the dimensional
patible material is still an unsolved problem. stability, following the polymerization shrinkage,
At present, composites are not used in clinical prac- wear resistance, and mechanical properties. Wear
tice but there are some studies on the possibility to and mechanical properties strongly depend on the
use these materials as vascular grafts. Porous poly- filler-matrix adhesion; microcavities, resulting from
ethylene terephthalate (PET), polytetrafluoroethyl- material detachment, could play a decisive role in
ene (PTFE) or polyurethane (PU) impregnated the adhesion of bacterial plaque. Finite elements
with collagen or gelatin have been studied (1). analyses have shown that the maximum stresses
Graft impregnation allows the preclotting proce- generated by shrinkage are in the region of the in-
dure to be avoided which is needed to minimize terfaces (3). The higher the interface stiffness, the
blood leakage; it improves the dimensional stability lower the deformation of the restorative material,
of the graft and seals the pores. After the collagen but the stresses increase.
and gelatin in vivo degradation, the porous wall of The research is devoted to optimize the perfor-
the graft allows the ingrowth and firm anchorage of mance of the material and to overcome problems
the host tissue to the material. An arterial prosthe- associated with the composites that are currently
sis made of PU fibers and a mixture of PU and used. The monomer-polymer conversion greatly af-
PELA (a copolymer of lactid acid and polyethylene fects the mechanical and biological properties of
glycol (PEG)) has been obtained by filament wind- dental composites and can be varied and controlled
ing technology (2). At the time of implantation the by changing the cure conditions (4, 5, 6). Low de-
graft is dense preventing any blood loss, but the grees of conversion during the resin polymerization
matrix is resorbable in vivo, thus resulting in the are responsible for the loss of mechanical, chemical
formation of a porous wall during the healing and physical properties. TEGDMA release has been
process, that allows the tissue ingrowth into the mainly studied and the quantity released was some-
pores. Fiber orientation, amount and properties times higher than the cytotoxic limit. The cytotoxic
are selected in order to produce elastic and me- effects became less important when the curing time
chanical properties that closely match the proper- of the resin was increased and with preincubation
ties of the natural vessel. periods in a biological medium (7).
Wear is still a cause of clinical failure, particularly in
2. APPLICATIONS IN DENTISTRY high stress areas such as molar restorations. The
wear rate determined by occlusal loading of some
The hard dental tissues, mainly enamel and den- commercial dental composites has been tested with
tine, are natural composites made of collagen and respect to the reinforcement particles dimensions
hydroxyapatite (HA) microcrystals. The use of (8). Wear rate for composites with small particles

4
Salernitano and Migliaresi

was higher than for those with large particles. The reinforced with silica-zirconia particles, has been
in vitro experimental results do not reflect exactly tested to investigate the effect of moisture on the
the in vivo behavior of the materials because the ef- stability of the matrix-filler interface (16). The ad-
fects of feeding and patient’s conditions are not dition of a filler increases the moisture sorption.
considered. A composite material may perform sat- The presence of a silane coupling agent improves
isfactorily in one patient while, in another patient, the material stability against the hydrolytic degra-
the same material may wear, degrade or fracture. dation. Filler particles of small dimension (<20 µm)
The consumption of alcoholic beverages, for exam- lead to a better surface finish, but are less resistant
ple, produces damages in the composite because to hydrolytic degradation (11).
the alcohol acts as a plasticiser of the matrix (9). The possibility of aligning the filler particles using
Most research efforts are devoted to overcoming an electric field has been analyzed to improve the
the problems related to the polymerization shrink- mechanical properties of dental composites (17).
age of the composite matrix (10). The polymeriza- The analyzed matrix consisted of 90% UDMA and
tion kinetics appear to be the most important para- 10% 1,6-hexanediol dimethacrylate (HDDMA), as
meter contributing to the magnitude of the inter- diluent agent, and the filler was silanated silica-zir-
nal stresses. The stress distribution is nearly the conia. The alignment of the reinforcement increases
same in self - and light-curing composites but the both the elastic modulus along the alignment di-
magnitude of the internal stresses doubles in light- rection and the maximum compressive stress.
cured composites. The addition of inorganic filler Some studies are dedicated to the development of
particles reduces matrix shrinkage, while diluent innovative materials to be used in posterior fillings
monomers with a molar volume lower than that of and multiple-unit restorations. An antibacterial
Bis-GMA, as TEGDMA, increase matrix shrinkage monomer (MDPB) has been incorporated in
and water uptake causing decay of the mechanical Bis-GMA based composites to improve durability
properties. Bis-GMA dimensional stability and me- and stability (18). The results have shown that the
chanical properties may be improved by using antibacterial effect did not decrease even after ag-
monomers with a greater molar volume (11). Low ing in a wet environment for a long period and the
viscosity dimethacrylate monomers requiring less material did not release antibacterial components
diluent monomers have been studied (12). Many in the oral cavity. Improvements in the mechanical
research efforts are also directed to the develop- properties, mainly brittleness and toughness, have
ment of non-contracting resins and fillers with ex- been achieved with an innovative fibrous reinforce-
pansion capacity, but the optimal material has not ment (19, 20). The analyzed matrix consisted of 50
been found yet (13). wt% Bis-GMA and 50 wt% TEGDMA, while the
Adhesion between the matrix and the filler is a crit- filler was silicon carbide or nitride whiskers. Silica
ical issue for material performance. Coupling particles were fused on the whiskers to facilitate
agents improve bonding between composite con- silanisation, to minimize whiskers entanglement
stituents. Different coupling treatments have been and to enhance whiskers retention in the matrix by
analyzed to evaluate the reduction of contraction providing roughness. Silicon nitride whisker rein-
stresses caused by resin polymerization. The tested forcement confers a twofold improvement in the
matrix was made by 25 wt% Bis-GMA, 35 wt% flexural strength of dental composites, offering, at
TEGDMA and 40 wt% urethandimethacrylate the same time, a high elastic modulus and fracture
(UDMA); the reinforcement was unsilanated, non- toughness, and a low brittleness with respect to cur-
functional silanated and functional silanated silica rent dental materials. Silicon carbide whiskers dou-
particles (14). Particles not treated with a function- bled the fracture toughness with respect to the cur-
al silane agent do not bond to the matrix, providing rent dental composites, while the brittleness was re-
internal sites for stress relief. Hardness and mois- duced to one half. HA-Ca polycarboxylate compos-
ture sorption measurements can be used to moni- ites are studied for dental restorations (21). The
tor the properties of dental composites. Hardness is material has shown good adhesion to teeth wall. HA
related to the stability of the resin-filler interface addition improves biocompatibility and mechanical
and may monitor the effectiveness of silanation properties. In situ composites made of porous ap-
process (15). A composite made of a blend of atite and 40 wt% PMMA have been studied for ap-
UDMA and ethylene-glycol dimethacrylate, rein- plications as dentine restoration materials (22). A
forced with glass and silica particles, has been test- reinforcement shaped as a three-dimensional fi-
ed. The hardness increases with volume fraction of brous scaffold has also been studied (23). The
the filler and it is significantly higher for silanated fibers are made of 25 wt% alumina and 75 wt% sili-
filler than the equivalent unsilanated filler. UDMA, ca and the matrix is based on Bis-GMA and

5
Composite materials for biomedical applications: a review

TEGDMA. The reinforcement is well incorporated 3.1 Dental implants


into the matrix, reduces the polymerization shrink-
age and improves the wear resistance. Further work Dental implants have been developed to over-
is required to optimize the material production. come the problems associated with bridges and
Composite posts made of unidirectional carbon removable dental prostheses. The damaged or
fibers embedded in an epoxy-resin matrix have missing tooth is replaced by an artificial perma-
been proposed in (24, 25). Minimizing the mis- nent implant. Research and clinical practice are
match of the elastic modulus between the post and devoted to reach a total bone regeneration and
the dentine reduces the occurrence of root frac- to inhibit both migration of epithelial cells to
tures and restoration failures. While traditional the implant and fibrous encapsulation.
metallic posts are subject to corrosion and fatigue Composite materials have been studied and de-
failures, composite posts meet the requirements of veloped mainly for application as endosseus ele-
mechanical strength and corrosion resistance. An ment. Composites made of SiC and carbon or
ideal post should have varying stiffness along its carbon fibers reinforced carbon have been pro-
principal direction: higher stiffness in the upper posed (1). These materials have some advan-
section, for better retention and rigidity of the tages over ceramics and metal alloys: they com-
restoration, and lower stiffness, close to that of den- bine sufficient strength with a low elastic modu-
tine, in the lowest section, to avoid dangerous stress lus, similar to that of natural teeth, minimizing
concentration. A functional composite post, with a the alteration of the stress field affecting the
constant cross-sectional geometry and made of long-term success and host response. Moreover,
epoxy resin reinforced with unidirectional carbon they have far superior fatigue properties. Some
fibers, at different concentration along its axis is studies have addressed the combination of Ti
under investigation (1). with HA to optimize and satisfy both mechanical
requirements and biological response of the host
2.2 Fixed and removable dental prostheses tissue to the implant. Graded composites com-
bining Ti and HA has been tested in (27). The
Fixed bridges and removable dental prostheses are graded structure in the longitudinal direction
used to replace one or more teeth, thus restoring contains more Ti in the upper section and more
the masticatory, phonetic and aesthetic functions. HA in the lower section. As a matter of fact, in
Their main disadvantages are: fixed bridges inter- the upper section the occlusal force is directly
fere with the adjacent teeth through the points of applied and Ti offers the required mechanical
attachment, removable dentures are uncomfort- performance; in the lower part, which is im-
able and do not transfer the occlusal stresses to the planted inside the bone, the HA confers the
bone. bioactive and osteoconductive properties to the
Some composite materials are used as bridges material. This composite has been tested in vivo,
(carbon, Kevlar, ultra high molecular weight poly- no inflammation has been observed and new
ethylene (UHMWPE) or glass fibers reinforced bone has grown at the interface between the
PMMA) and as removable prostheses (glass fibers bone and the implant. Ti alloy substrate has
reinforced polycarbonate (PC), polyamides, been combined also with HA granules spread
polypropylene (PP) or PMMA) (1). Good results, over the surface (28), but further studies are
in terms of mechanical properties and aesthetic needed to evaluate the biofunctionality and bio-
appearance, have been obtained, for applications compatibility of this material.
as bridges, combining two different composite Other studies are devoted to guided tissue re-
materials made of a methacrylic matrix rein- generation. A composite membrane consisting
forced with glass fibers and inorganic particles of polyethylene glycol terephthalate (PEGT)
(26). and polybutylene terephthalate (PBT) copoly-
mer reinforced with 30 wt% HA grains has been
3. APPLICATIONS IN ORAL AND MAXILLOFACIAL SURGERY proposed in (29). This composite has excellent
mechanical properties and in vivo experimental
The most important reasons for oral and maxillofa- results reveal good biocompatibility and a grad-
cial surgery are: replacement of damaged or miss- ual degradation, mainly influenced by the
ing teeth, replacement of resorbed bone tissue, re- PEG/PBT ratio. The experimental results are
placement or repair of temporomandibular joint promising but more in vivo testing and clinical
and facial bones and fixation of fractured facial studies have to be performed before clinical ap-
bones. plication.

6
Salernitano and Migliaresi

3.2 Temporomandibular joint prostheses Fig. 1 - Miniplates made


of 40 wt% u-HA rein-
forced PLLA.
Maxillofacial surgery is necessary for patients af- (Reprinted from Biomateri-
flicted with arthritis of the temporomandibular als, Vol. 22. Shikinami Y,
joint. Wear is one of the most important reasons for Okuno M, Bioresorbable de-
long-term failure of temporomandibular joint pros- vices made of forged compos-
theses. At present, the composite materials are not ites of hydroxyapatite (HA)
particles and poly-L-lactide
used in clinical practice. A composite cup made of (PLLA): Part II: practical
PTFE and carbon or alumina has been tested as an properties of miniscrews and
alternative to UHMWPE cup, but the clinical results miniplates, 3197-211, copy-
have shown significant inflammatory response near right 2001, with permission
the implant site (30). Further studies are needed to from Elsevier Science).
develop the optimal material and prosthesis geom-
etry.

3.3 Cranial bones repair

Fracture fixation devices are employed to guaran-


tee rigidity during the healing process. Intense re-
search activity has been devoted to the use of bioac-
tive ceramics, mainly TCP and HA, because they
have composition and morphology close to those of
the mineral phase of natural bones. These osteo-
conductive materials promote and assist the heal-
ing of the bone defect, by acting as a temporary
scaffold for bone ingrowth. A biodegradable and
osteoconductive composite made of tricalci-
umphosphate (TCP) particles and gelatin has been
proposed in (31). This material has been tested
in vivo with good results. It has shown itself to be
biocompatible, osteoconductive and biodegrad-
able, with no need for a second surgical operation
to remove the device after healing has occurred.
Further research is needed to obtain the repair of
large defects. Miniscrews and miniplates made of
poly-L-lactid acid (PLLA) matrix reinforced by
u-HA (raw hydroxyapatite neither calcined nor sin- folds with cells may provide an alternative to both
tered) particles, respectively 30 wt% and 40 wt%, organ transplantation and implantation of me-
have been manufactured and tested (Fig. 1) (32). chanical medical devices unable to perform all
They have shown easy handling and shaping ac- functions of a tissue or an organ.
cording to the implant site geometry, total resorba- Some composite materials have been studied to ver-
bility, good ability to bond directly to the bone tis- ify their performance in applications as scaffold for
sue without interposed fibrous tissue, osteoconduc- cellular growth in tissue engineering. Some studies
tivity, biocompatibility and high stiffness retainable are devoted to the development of a scaffold which
for the period of time necessary to achieve bone combines specific biological properties and electri-
union. cal characteristics, improving bone and nervous tis-
sue regeneration. Composites made of hyaluronic
4. APPLICATIONS IN TISSUE ENGINEERING acid and polypirrone have been synthesized and
characterized (33). The composite has been tested
Tissue engineering is an emerging area in medicine in vitro and in vivo showing good results. For tissue
involving cells manipulation to promote the regen- engineering of bone and cartilage, a composite
eration and healing of defective natural tissues or consisting of a three-dimensional mesh composed
the development of biological substitutes that re- of 80 wt% polycaprolactone (PCL) fibers with 20
store, maintain or improve tissue and organ func- wt% HA particles on the surface has been evaluat-
tions. The combination of natural or synthetic scaf- ed (34). The ideal scaffold material has not been

7
Composite materials for biomedical applications: a review

collagen fibers, giving the bone strength and flexi-


bility, and an inorganic portion, composed of HA
microcrystals and mineral salts, conferring hard-
ness to the bone. The bone tissue is continuously
replaced and remodelled according to the applied
stresses by the osteoblasts and the osteoclasts, and it
is able to self-regenerate after injuries. However,
when injury is too severe and loss of volume is too
high, healing is incomplete, fibrous tissue forms,
mechanical functionality is not restored and bone
grafts are necessary. The ideal bone graft is repre-
sented by autografts, but their amount is limited,
their properties and shape do not match exactly
those of the bone to be replaced, and multiple sur-
gical operations are needed. The use of allograft is
accompanied by biological and mechanical difficul-
Fig. 2 - Osteoblasts adhesion on HAPEXTM surface. ties and the risk of infection transmissions exists;
(Reprinted from Acta Mater, Vol. 46. Bonfield W, Wang M, Tan- for these reasons synthetic bone grafts are under
ner KE, Interfaces in analogue biomaterials, 2509-18, copyright extensive investigation.
1998, with permission from Elsevier Science). Some studies are devoted to the development of a
composite graft consisting of demineralised bone
developed yet and further investigations are need- powder packed between two collagen layers (35).
ed. Other studies deal with the combination of PCL The laminate has been tested in vitro and in vivo
and HA with different morphology. The composite showing cell migration through the collagen layers
is obtained by infiltration of ε-caprolactone and the interaction with the bone demineralised
monomer into porous apatite blocks and in situ powder.
polymerization (22). The material is biodegradable Great attention is payed to the use of bioactive ce-
and may have application as cancellous or trabecu- ramics because of their ability to bind to the natur-
lar bone replacement material or for cartilage re- al bone tissue. The contact with blood plasma in-
generation. The polymer molecular weight increas- duces the surface coating with a bone-like HA layer
es with the polymerization time, leading to an im- where the osteoblasts can proliferate. Most studies
proved compressive strength. deal with the combination of high density polyeth-
ylene (HDPE) and HA particles as bone replace-
5. ORTHOPEDIC APPLICATIONS ment materials (1, 36-41). The resulting composite
has been tested in vitro, in vivo and clinically evalu-
Orthopedics is the medical area where application ated. The successful results have allowed its com-
of the biomaterials is highly developed both for mercialization in 1995 with the trade name of
commercialization and research purpose. The use HAPEXTM. The effects of the reinforcement con-
of composites in orthopedics offers a variety of new tent, the size of the HA particles and the addition
implant design and the possibility to tailor specific of coupling agents on the biological and mechani-
device properties. Composite materials can repro- cal properties have been analyzed. The range of HA
duce both the macroscopic and microscopic struc- fraction has been optimized between 20 and 40
ture and the most important mechanical properties vol%, giving a bioactive and fracture tough implant:
of the natural tissues. HA fractions less than 20 vol% caused the material
Composites materials are studied and tested to im- to become inert promoting a fibrous encapsulation
prove the performance and the long-term stability of the implant and a ductile-brittle fracture transi-
of femoral stems and bone cement, to replace car- tion exists at about 40 vol%. Composites with small
tilage, to reconstruct tendons and ligaments and as HA particles show a high torsional modulus, ten-
bone grafts. sional modulus and tensile strength, but a low
strain to failure. HAPEXTM stiffness and strength are
5.1 Bone graft below the values associated with cortical bone; con-
sequently, this bone substitute cannot be used in
The bone tissue combines a cellular component, major load-bearing applications. The experimental
the osteocytes, and a matrix. The matrix is a com- results have shown a good adhesion and prolifera-
posite made of an organic portion, composed of tion of osteoblasts on HA surface particles (Fig. 2)

8
Salernitano and Migliaresi

(37), increasing with the HA content. The mechan- use in bone regeneration (48). The matrix porosity
ical performance depends on the filler-matrix in- facilitates the migration of osteoblasts from the sur-
terface which affects the long-term success and sta- rounding bone to the implant site. The HA fibers
bility in the biological environment. The examina- enhance material mechanical properties and pro-
tion of the fracture surfaces revealed that only me- mote the bone regeneration. Further studies are
chanical bond occurs between HA and polyethyl- needed for the optimization of the composite graft
ene (PE). To improve the mechanical performance porosity to allow cell seeding without loss of me-
of HAPEXTM, it is necessary to introduce a coupling chanical properties.
agent at the filler-matrix interface for an effective Among the bioactive ceramics, TCP, as well as HA,
stress transfer and to promote chemical bonding stimulates great interest for application as bone
between the reinforcement and the matrix. Further graft. A bone replacement composite made of
improvement could be obtained with the molecular α-TCP reinforced with polyammide (PA) fibers has
orientation in the polymer matrix and the addition been proposed in (49). The addition of fibers pro-
of woven, high performance PE fibers. Many stud- duces a moderate increase of the compression
ies deal with the development of a bioactive mater- strength because of the weak coupling of the fibers
ial for bone replacement with composition and bi- with the matrix. Higher compression strengths can
ological response similar to that of natural bone. be obtained only through modification of fiber sur-
Composites obtained by the combination of HA face or by using coupling agents. Composites con-
particles and collagen fibers have been analyzed in stituted by TCP and glutaraldehyde cross-linked
(42). The graft has revealed a very high biocom- gelatin have been analyzed and tested in vitro to
patibility, excellent biological properties and good measure the material cytotoxicity (50, 51). The ex-
mechanical performance (43). HA/alumina com- perimental results have shown that the glutaralde-
posites have been proposed as bone replacement hyde cross-linking agent added into the composite
materials (44). In vivo results have shown that no should be lower than 8% to decrease the toxicity on
soft tissue is present, the composite bone-bonding the osteoblasts and to avoid the inhibition of cellu-
is a function of the content of HA, while the me- lar growth caused by the release of residual or un-
chanical properties are connected to the alumina cross-linked glutaraldehyde. TCP has been also
content. P2O5 glass reinforced HA composites have combined with biodegradable PP fumarate to veri-
been developed to synthesize a bioactive graft ma- fy the possible application as temporary replace-
terial with a stiffness close to that of a natural bone ment for trabecular bone (52). In vivo results
(45). The elastic properties are strongly dependent proved that the composite is biocompatible and al-
on the material porosity. Some studies are devoted lows a progressive new bone growth inside the de-
to the development of partially resorbable compos- grading material. The composite maintains a com-
ites made of a polymeric matrix, such as PEG, PBT, pressive strength and modulus greater than the
PLLA, polyhydroxybutyrate (PHB), alginate and minimum value for trabecular bone replacement.
gelatin, and a bioactive filler (1). The material In addition to HA and TCP, bioglasses are also stud-
achieves a good integration into the bone since the ied as bone replacement materials. Composite ma-
matrix resorption yields a large number of bioactive terials have been prepared using 37 wt% bioactive
particles coming in contact with the tissues. A cou- glass powder, 27 wt% PLA, 27 wt% PMMA and 9
pling agent was added to the composite made of wt% antibiotic, gradually released to prevent infec-
PEG/PBT copolymer (ratio 70/30) matrix and HA tions and inflammations (53). In vitro experimental
reinforcement improving the mechanical proper- results have shown the growth of an apatite-like lay-
ties by covalent bonding of the HA with the poly- er on the composite surface. Further investigation
mer matrix (46). Elastomeric D,L-lactide and is needed to evaluate the long-term effects of the
ε-caprolactone copolymers (ratio 60/40) rein- degradation products, and to verify whether the
forced with HA powder was analyzed to character- growth of a surface apatite layer inhibits the antibi-
ize the effect of the HA content (47). The incorpo- otic release. Bioglass reinforcements have been
ration of HA reduces the degradation rate and has tested also in combination with a PE matrix (37).
effect on the mechanical and handling properties. The matrix/reinforcement adhesion is weak be-
HA reinforcement morphology different from par- cause there is only mechanical coupling. The com-
ticles, such as HA fibers, have been studied and posite has shown mechanical properties very close
characterized. Biodegradable composite foams of to that of natural spongy bones with bioglass con-
PLGA, a copolymer of polyglycolic acid (PGA) and tent higher than 30 vol%. The adhesion between
poly lactid acid (PLA), (PLA/PGA ratio 85/15) re- the matrix and the reinforcement is weak, if com-
inforced with HA short fibers have been tested for pared to HA/PE composites, and the elastic modu-

9
Composite materials for biomedical applications: a review

may offer the desired high strength and bone-like


elastic properties. Composite fixation devices based
on a thermosetting matrix may induce toxic reac-
tions following the release of unreacted monomers
(1). Thus, the research activity is oriented to the de-
velopment of thermoplastic composites, such as
carbon fibers reinforced PMMA, polysulfone, PP,
PE, PBT or polyetheretherketone (PEEK) (1). Me-
chanical and biocompatibility tests have shown
good results, but there are not yet enough data on
long-term in vivo performance.
A novel composite made of unidirectional carbon
fibers, embedded in a matrix of liquid crystalline
Fig. 3 - Internal fixation devices made of u-HA reinforced PLLA. polymer, has been proposed in (56). This material
(Reprinted from Biomaterials, Vol. 20. Shikinami Y, Okuno M, has been tested in vitro and in vivo showing a flex-
Bioresorbable devices made of forged composites of hydroxyapatite
(HA) particles and poly-L-lactide (PLLA): Part I Basic characteris- ural strength higher than that of some metals used
tics, 859-77, copyright 1999, with permission from Elsevier Science). in orthopedic applications, an elastic modulus
quite close to the corresponding value of cortical
bone and a good chemical resistance. The initial
mechanical properties are retained after implanta-
lus is low, but the osteoconductive properties are tion.
high and this composite needs short times to be in- The use of composite materials made of a polymer-
tegrated with the bone tissue surrounding the im- ic biodegradable matrix is an interesting research
plant site. field. Their main advantages over metals are: no
Carbon fibers-reinforced carbon has also been test- second surgical operation is necessary, the frac-
ed in vivo (54). The results have shown that a me- tured bone has a low tendency to refracture after
chanical bonding between the implant and the host the removal of the implant, the device may be en-
tissue does exist, mainly due to the initial porosity gineered to degrade at a rate allowing a gradual
of the material, and there was no connective tissue transfer of the load from the implant to the healing
encapsulation around the implants. bone. Furthermore, there are no tissue reactions
A composite implant of a coral (mainly CaCO3) caused by metallic corrosion and drugs can be in-
and collagen has been tested in vivo for use in the serted and gradually released into the surrounding
healing of bone defects (55). There was no infec- tissues. Totally bioresorbable internal fixation de-
tion after implantation and the implant is well inte- vices made of PLLA reinforced with raw u-HA par-
grated in the natural tissue with no interposed fi- ticles have been manufactured and characterized
brous tissue. (Fig. 3) (57, 58). The composite has ultra-high
strength, excellent processability and an elastic
5.2 Bone fracture internal fixation devices modulus close to that of natural bone. Moreover, it
can retain its high strength during bone healing,
Internal fixation devices are temporarily implanted shows optimal degradation and resorption behav-
inside the body to hold together the bone frag- ior, and maintains osteoconductivity and bone
ments and promote healing. bonding capability. This composite has been tested
The critical issues associated with the use of metal- in vitro, to analyze the degradation process, and in
lic internal osteosynthesis devices are: metals are vivo, to verify the biocompatibility and the bioactiv-
exposed to corrosion in the physiological environ- ity, showing good results.
ment and the stiffness mismatch between the bone Composites made of PLA reinforced with HA
and the metallic implants induces the stress-shield- fibers, with almost stoichiometric composition,
ing phenomenon affecting bone remodeling and have been studied in (59). The composite is able to
healing process. The research spent in this field is consume a large amount of energy in the fracture.
justified with the assumption that an ideal internal Polymeric composites reinforced with bioglass par-
fixation device should have a high mechanical ticles have been studied and tested in vitro to verify
strength to avoid fracture, but a stiffness close to the bioactivity and osteoconductivity after immer-
that of the natural bone tissue (but overall rigidities of sion in physiological solution (60). PLA composite
device and bone and not elastic moduli should be com- rods reinforced with 15-25 wt% bioglass particles,
pared; Author’s note). Polymeric composite materials PLA plates coated with bioglass spheres, with a total

10
Salernitano and Migliaresi

glass content of 17.5 wt%, and polyethyleneoxide prosthesis because of UHMWPE wear, erosion and
(PEO)/PBT copolymer rods reinforced with up to creep deformation. To increase their long-term
40 wt% bioglass particles have been analyzed. All performance, many research efforts are devoted
these materials show a good bioactivity leading to both to improve the mechanical properties of
the formation of an apatite layer on the surface. UHMWPE, by adding reinforcements, and to de-
Bioglass reinforced PEO/PBT has shown the best velop new alternative materials. Acetabular cups
and fastest apatite formation. made of UHMWPE, reinforced by carbon fibers or
A critical issue of biodegradable matrices is the UHMWPE fibers have been investigated (1, 30), but
degradation rate control during fractured bone the effect of the fibers on wear behavior are not
healing. The lost of device mechanical properties clear yet, and the reported results are contradicto-
during the degradation should be synchronized ry. A carbon reinforced PEEK has been proposed as
with the healing rate. At present, the non optimal an alternative for UHMWPE (61, 62). Experimental
mechanical properties limit the application of results have shown that the wear rate decreases with
biodegradable composites to internal fixation de- high fiber content, and that the best option for
vices used in reduced load conditions. Neverthe- good wear characteristics and dimensional stability
less, the future perspectives are promising. is an acetabular insert made of 30 wt% pitch-based
carbon fibers reinforced PEEK and a zirconia head.
5.3 Joint prostheses With this combination, the wear rate has been re-
duced by almost two orders of magnitude, com-
The use of composite materials in artificial joints is pared to a conventional UHMWPE/metal or
a promising research field. The implant properties UHMWPE/ceramic combination. Carbon fibers re-
can be varied and tailored to suit the correct me- inforced epoxy resin has been analyzed as an or-
chanical and physiological response. Prostheses thopedic bearing surface for acetabular cups in
with stress and strain distribution close to physio- (63). The combination of alumina femoral heads
logical ones have more chances of long-term stabil- and composite cups results in excellent long-term
ity and clinical success. The current results are behavior minimizing the wear debris and biological
promising, but more experience is needed regard- response. The wear rate is respectively 5 and 30
ing the clinical use of composite artificial joints. As times lower than UHMWPE cups coupled with alu-
a matter of fact, to carry out clinical experiments mina and UHMWPE cups coupled with metal.
extended periods of time are needed and some Composite materials have been investigated also as
concerns persist on the improvement in biocom- coatings or as the main constituent for femoral
patibility using composite materials. stems. Bioactive composite coatings have been ob-
tained combining a bioglass and a titanium alloy
5.3.1 Hip (Ti6Al4V) (64). The bioglass gives osteoconductive
properties to the coating, while Ti makes it tougher.
The hip prosthesis is the most implanted artificial For metallic prostheses with a bioactive coating
joint. Clinical data show that about 90% of artificial there is still a mismatch between the natural bone
hip joints are successful for the first 10 years. Even- tissue and implant mechanical properties. Compos-
tual revision surgery reduces the long-term success. ite femoral stems have been developed to reduce
The main failure reasons of total hip replacements the problems associated with the stress shielding
are: the stress shielding phenomenon, the relative and the micromotion. Stems with a controlled stiff-
movement of the prosthesis, leading to the devel- ness, close to that of natural bone, can be obtained
opment of a soft tissue interface between the bone by combining a stiff material with a more flexible
tissue and the prosthesis, and the presence of wear one and varying the thickness of layers. A femoral
particles that may induce adverse biological reac- stem made of a metallic cobalt-chrome core sur-
tions in the body. Moreover, metallic components rounded by a composite layer has been analyzed in
undergo corrosion phenomena in the physiologi- (65). The composite layer was made of an epoxy
cal environment, which may induce stem fracture resin reinforced with carbon and glass fibers. The
and cytotoxic and allergenic processes. studies on femoral stems entirely made of compos-
Composite materials are not currently used in clin- ites have shown good results. The strength of com-
ical practice for total hip replacement, but they are posite prosthetic components may be changed
studied with great interest for application as ac- without affecting the stiffness and the modulus can
etabular cup and femoral stem. Acetabular cups are be varied without altering the strength. Finite ele-
made of ultra high molecular weight polyethylene ments analyses reveal that composite stems allow a
(UHMWPE) and are still the weakest link in a hip more uniform and effective stress transfer, close to

11
Composite materials for biomedical applications: a review

the physiological one, than metallic stems (1, 65- ial component to overcome the problems associat-
68). Nevertheless, there are two limiting factors: ed with UHMWPE creep and wear. Creep deforma-
given an applied load, higher strains are generated tion induces sinking of the prosthesis while wear
inside more flexible implants and the shear stresses particles induce a foreign body reaction. However,
at the interface between the implant and the bone the results are contradictory and not clear enough
is high for those implants with a low stiffness. Car- to foresee the long-term material performance. A
bon fibers reinforced PEEK is one of the most composite tibial component made of UHMWPE
promising composites considered for the femoral and UHMWPE or carbon fibers has been proposed
component (69). In vitro aging results have not (1). The reinforcement addition reduces the stress
shown a significant loss of compressive strength and concentration during the articular movement and
modulus. In vivo results have shown mechanical improves the mechanical properties. The results
properties very close to that of natural femurs, min- concerning the wear resistance with carbon fibers
imal tissue reaction and a mechanical stability of reinforcement are contradictory. Hence, some
about 6 months (1). Polysulfone and carbon rein- studies are oriented to combine a UHMWPE sur-
forced with carbon fibers have been also proposed face with a composite substrate so that the wear re-
for femoral stems (1). The experimental results sistance would not be affected. No significant dif-
have shown fast bone bonding, when compared to ference in the wear performance has been ob-
metallic prostheses, a good stability without the re- served with UHMWPE fibers.
lease of soluble elements and a high static and fa-
tigue resistance. Some studies are devoted to the 5.3.3 Bone cement
analysis of laminate composites because the loads
applied to the hip joint are not unidirectional. A The bone cement is a grouting material used to en-
composite stem made of 120 epoxy resin laminae, sure a firm fixation of the joint prostheses. The
reinforced with carbon fibers, stacked according to most widely used commercial formulations are
a specific sequence has been tested (1). Ther- based on PMMA, are self-polymerizing and have
mosetting polymers may release toxic unreacted minimal adhesive properties. Thus the bonding
monomers in the surrounding tissues. Thus, ther- with the bone and the implant surface is a mechan-
moplastic polymers are preferred as composite ma- ical one consequent to the polymer setting and
trices. The use of polyetherimide (PEI) is very hardening. The critical issues of commercial bone
promising due to its excellent biocompatibility. cements based on PMMA are the exothermic na-
PEI reinforced with carbon and glass fibers has ture of polymerization, that may locally induce
been tested in vivo (70). Composite implants do bone necrosis, the shrinkage associated with the re-
not induce foreign body reactions and their re- action, that may lead to mechanical failure and in-
sponse is comparable to that of metallic devices. A stability associated with the deterioration of the ce-
composite laminate femoral stem made of a se- ment/implant or cement/bone interfaces, and the
quence of laminae of PEI reinforced with carbon release of cytotoxic unreacted monomers and addi-
and glass fibers has been manufactured and char- tives in the surrounding tissues and in the blood
acterized (71). The laminate prosthesis is charac- stream.
terized by a stiffness similar to that of the sur- Much effort has been made to improve the me-
rounding bone, ensuring a load transfer between chanical properties of bone cement and to over-
the implant and the bone similar to the physio- come the key problems. The first attempts tried to
logical one, and by a high strength, preventing the combine PMMA with fibrous reinforcements, such
implant from fracture. as carbon, Kevlar, stainless steel, Ti, glass or PE
fibers (1, 30). The addition of fibers resulted in big
5.3.2 Knee improvements in the mechanical performance, but
fibrous cements have not been accepted in clinical
The knee joint is the most exposed to traumatic practice because of a loss of material workability,
and degenerative injuries. Knee geometry and consequent to the viscosity increase, and the diffi-
kinematics are more complex than those of hip, culty of obtaining a uniform distribution of the re-
even if with lower loads. This is why different inforcement inside the matrix. Better results have
geometries and types of knee joint replacements been obtained with particles reinforced cements.
have been developed and the long-term success of The performance of a partially resorbable bone ce-
the implants is lower than for hip replacements. ment made of a gelatin reinforced with TCP parti-
At present, composite materials are not used in cles has been evaluated (1). This composite allows
clinical practice. They have been tested for the tib- the bone ingrowth and the direct chemical bond-

12
Salernitano and Migliaresi

ing between the TCP particles and the bone tissue 5.4 Artificial tendons
following the matrix resorption. On the other
hand, the mechanical properties of partially re- The tendons can be considered as unidirectional
sorbable bone cements are lower than that of fibers reinforced composites made of collagen
PMMA cement. The introduction of a bioactive fibers, aligned along the principal direction and im-
phase may enhance the prosthesis fixation by en- mersed in an elastine-mucopolysaccharide hydro-
couraging the direct bone apposition rather than gel. When stress is applied the collagen fibers line
the encapsulation of the implant by the fibrous tis- up along the stress direction; if the stress is higher
sue. Bone cements made of PMMA and bone or than the fibers strength resistance, a fracture oc-
bioglass particles have been proposed (1). The me- curs. Hence, the mechanical behavior depends on
chanical properties and the bioactivity of cements the matrix properties at low stress values and on
constituted by PMMA and HA have been also inves- fibers properties at high stress values. The tendon
tigated (72, 73). The addition of HA allows the di- tissue allows a large extensibility without perma-
rect bone apposition and offers a better substrate nent deformations. Most of the commercial ten-
for osteoblasts attachment and proliferation, com- dons prostheses undergo mechanical failure due to
pared to a PMMA cement. As a drawback, the an inadequate fatigue, especially bending and fric-
PMMA/HA cement has shown a low flexural, com- tion, resistance.
pressive and tensile strength. Further investigations Great attention is given to the design and fabrica-
are needed to optimize the PMMA/HA ratio in or- tion of composite tendon prostheses reproducing
der to obtain improved mechanical performance. the structure, resistance and flexibility of the natur-
A composite cement based on PMMA and HA par- al tissue. Most of the artificial tendons studied until
ticles has been compared to a cement made of now are based on polyesters and hydrogels. The
PMMA and bioglass particles (30 wt%) (74). When mechanical behavior of a composite made of poly-
implanted in vivo, PMMA disturbed the osteocon- 2-hydroxyethylmethacrylate (PHEMA) matrix and
ductive bone formation on the surface of bioactive PET fibers reinforcement has been studied in (79,
materials. This effect was less evident with bioglass 80). The composite reproduces the stress-strain
than with HA. curve showed by the natural tendons under low
New composite cements with matrix different from strains. A different mechanical response can be ob-
PMMA have been developed. Composites with poly- tained varying the alignment of the fibers. A com-
ethylenmethacrylate (PEMA) based matrix and HA posite made of ethylene-butene copolymer and
reinforcement cement have been tested (75, 76). UHMWPE has been tested in (81), to characterize
The presence of HA increases the matrix fatigue the fatigue resistance as a function of the copoly-
and flexural properties and reduces the water up- mer composition and the fibers alignment. Good
take responsible for the release of unreacted long-term performance is ensured by more
monomers and polymerization residues, the break- branched copolymers and high angles between the
down of the polymer itself, the penetration of mi- reinforcement and the applied load direction. A
croorganisms and the decrease of mechanical prop- composite material based on polyester and chitin
erties. In vitro experimental results have shown that has been analyzed to evaluate chitin effects (82).
this composite cement produces lower temperature The chitin is a wound healing accelerator and, in vivo,
at bone/cement interface and gives higher conver- it induces collagen and elastic fibers in the pros-
sion rates than commercial PMMA cements. A com- theses. Further investigation is needed to clarify this
posite cement based on Bis-GMA and 70 wt% of alu- mechanism.
mina powder has been tested in vivo, showing an The surgical and long-term implant success de-
excellent osteoconductivity and a high mechanical pends on the implanted materials, but also on the
strength (77, 78). The alumina fillers were sur- firm fixation of the prosthetic element to the bone.
rounded by bone-like tissue and no interposed soft The biological attachment of autogenous tendons
tissue was observed. to the bone tissue has been studied in vivo by injec-
The ideal bone cement has not been developed yet. tion of a composite made of 40 wt% collagen and
Among its characteristics, this material has to be easy 60 wt% powdered HA, between the grafted tendon
workable and should allow good adhesion to the and the bone tunnel (83). The collagen was gradu-
bone by penetrating into the internal cavities of the ally degraded and replaced by the regenerating
bone tissue. Also, the mechanical properties have to bone in direct contact with the grafted tendon with-
be adequate to the implant stabilization and should out an interposed fibrous tissue layer. The collagen
not prevent the bone remodelling, offering a low re- fibers of the grafted tendons penetrate the newly
action temperature and a high dimensional stability. formed bone, increasing the implant stability.

13
Composite materials for biomedical applications: a review

Fig. 4 - Commercial artifi-


cial ligament explanted
because of fatigue failure
and synovitis onset.
(Reprinted from Biomateri-
als, Vol. 21. Guidoin M-F,
Marois Y, Bejui J, Poddevin
N, King MW, Guidoin R,
Analysis of retrieved polymer
fiber based replacements for
the ACL, 2461-74, copy-
right 2000, with permission
from Elsevier Science).

Further investigations are needed to discover the lyzed for tendons replacement have been tested al-
ideal material for tendons replacement, which so for artificial ligaments applications, as the
might ensure long-term performance and stability. UHMWPE reinforced ethylene-butene copolymer
The complexity is increased by the variation of the (81) and the PET reinforced PHEMA (80). Experi-
geometry and properties of a tendon during mental results show that PET may induce synovitis.
growth and development, mainly the cross-section- Thus, terephtalate polyester woven fibers have been
al area, modulus and strength, as a function of the combined with an extracellular matrix based on
mechanical loading. collagen (85). The prostheses have been tested
in vivo showing no fracture, no signs of inflamma-
5.5 Artificial ligaments tion or foreign body reaction and the growth of ori-
ented fibrous tissue between the bone and the pros-
The ligaments have a complex fibrous anatomy and thesis.
a non-uniform structure and, as for tendons, their Artificial ligaments are being progressively dis-
geometry and properties vary during growth. missed, leading to a more frequent use of auto-
Most ligament injuries are related to the knee ante- grafts from rotulian tendons. Hence, in many cases,
rior cruciate ligament (ACL). Commercial artificial the prosthesis has the function to support the auto-
ligaments are polymeric or polymer-composite de- graft (augmentation devices).
vices. The success rate ranges only between 30 and
60%. Mechanical failures (Fig. 4) (84) are mainly 5.6 Artificial cartilage
due to the weak fatigue resistance, especially in the
aggressive human environment and under cyclic Cartilage replacement materials are used to repair
loads. The inadequate fiber resistance to abrasion congenital, developmental or acquired defects. A
and flexural and torsional fatigue, and synovitis are composite constituted by PET fibers reinforced
among the main reasons of long-term failures of PHEMA has been proposed to replace interverte-
artificial ligament. A biodegradable prosthesis, bral discs. It is possible to design a material with me-
made of PLLA and ialuronic acid esther, has been chanical properties comparable to those of natural
studied. The gradual degradation allows the re- discs by varying the fiber content and the matrix
placement of natural tissue. Some composites ana- composition. Further improvements for long-term

14
Salernitano and Migliaresi

performance are required. An innovative biocom- •there are no satisfactory standards yet for the test-
posite made of a single UHMWPE long fiber with a ing of the biocompatibility of composite implants
three-dimensional structure, coated with u-HA mi- because the ways in which the different compo-
croparticles, has been developed for potential ap- nents of a composite material interact to control
plications as articular cartilage, menisci and inter- the overall response to an implant are not com-
vertebral discs (86, 87). When implanted, the sur- pletely understood;
rounding tissues fill the textural space of this struc- •there are no adequate standards for the assess-
ture as a matrix, consequently forming a compos- ment of composites fatigue performance because
ite. The implant becomes a part of the natural tis- the fatigue behavior of composite materials are far
sue as a consequence of mechanical and physiolog- more complex and difficult to predict than that of
ical integration with the natural tissue. u-HA parti- traditional materials.
cles confer surface bioactivity, allowing enhanced The mentioned critical issues have to be solved be-
interactions with the surrounding natural tissues. fore widespread commercial use can be made of
The biocomposite has been tested in vivo showing composites in biomedical applications. However,
no fiber wear, no infection, good biocompatibility the future perspectives for the use of composite ma-
and mechanical properties, but a reliable method terials in medicine are encouraging and promising
to repair large defects has not been found yet. both in existing implants, where the use of more
flexible materials may enhance the prostheses sta-
bility, and in other important clinical areas where
CONCLUSIONS the availability of new materials may allow the de-
velopment of entirely new devices or surgical tech-
The use of composite materials for biomedical ap- niques. In any case the success of biomaterials re-
plications offers many new options and possibilities search and applications depends on the effective
for implants design. As a matter of fact, composite co-operation of clinicians, chemists, biologists, bio-
materials and components can be designed to obtain engineers and materials scientists.
a wide range of mechanical and biological proper-
ties. The implant structure and its interactions with
the surrounding tissues can be optimized by varying
the constituents, the type and distribution of the re-
inforcing phase and adding coupling agents.
Current applications of composite biomaterials in
medicine are still remarkably less than expected a
few years ago. In many biomedical applications, the
research and the testing of composites has been in-
troduced and highly developed, but only in a very
few cases an industrial production and commercial
distribution of medical devices partially or entirely
made of composites has started. The use of these
materials requires a complete understanding of the
objectives and limitations involved. The main criti-
cal issues are summarized as follows:
•there are not enough reliable experimental and
clinical data supporting the long-term perfor-
mance of composites with respect to monolithic
traditional materials;
•the design of composite materials and compo-
nents is far more complex than that of conven-
tional monolithic materials as a consequence of
the large number of additional design variables Address for correspondence:
that must be considered; Elena Salernitano, MD
•the available fabrication methods may limit the ENEA - Ente per le Nuove Tecnologie, l’Energia e l’Ambiente
possible reinforcement configurations, may be Centro Ricerche Casaccia - s.p.59
time consuming, expensive, highly skilled and Via Anguillarese, 301
may require special cleaning and sterilization 00060 S. Maria di Galeria (Roma) - Italy
processes; elena.salernitano@casaccia.enea.it

15
Composite materials for biomedical applications: a review

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