TISSUE ENGINEERING

Volume 6, Number 4, 2000

Mary Ann Liebert, Inc.

The Future of Biodegradable Osteosyntheses

FABIAN W. CORDEWENER, D.D.S., Ph.D., and JOHN P. SCHMITZ, D.D.S., Ph.D.

ABSTRACT

In the last 3 decades, much progress has been made in the development of biodegradable
osteosyntheses. Despite this progress, these materials are still only used in small numbers,
and the scope of their application has been limited. The limitations of biodegradable os-
teosyntheses mainly are related to problems with their mechanical properties and, in par-
ticular, biocompatibility. These problems need to be solved so that biodegradable osteosyn-
theses can perform up to their full potential and thus, eventually, make their general clinical
application routine. This paper presents a historical perspective on the development of
biodegradable osteosyntheses, discusses the successful developmental achievements and the
still-existing problems, and gives a perspective on their future developm ent.

INTRODUCTION

B have seen an enormous developm ent over the last 3 decades. There is
IOD EGR A DA B LE O STEO SY NTH ES ES
good reason for this effort, as biodegradable osteosyntheses offer a number of major advantages over
traditional metallic implants. Biodegradable osteosyntheses, by their nature, do not need removal after im-
plantation. Significant economical savings could be realized, because operation time can be spared and pa-
tients do not have to leave their working environm ent for surgery and recovery. 1– 3 More importantly, the
patient does not have to experience additional surgical discomfort and risk. In addition, biodegradable os-
teosyntheses do not interfere with radiotherapy, computer tomography, and magnetic resonance imaging.
Furthermore, complications that are associated with metal implants such as infection, sensitization, and pos-
sible mutagenic effects are obviated. 4– 7 Finally, the use of biodegradable osteosyntheses may prevent os-
teoporosis due to stress protection because they allow a gradual transfer of functional forces to the healing
bone. 8,9
At the present time, about 30 years after the first papers were published on the subject of polylactic acid
implants,10,11 the majority of surgical implants used are still metal, primarily commercially pure titanium
or titanium alloy. Biodegradable osteosyntheses have not replaced titanium and are currently used only in
limited numbers. Clearly, the advantages of biodegradable implants do not yet outweigh the advantages of
metallic implants. The purpose of this paper is to present a brief historical perspective of the development
of biodegradable osteosyntheses. This paper will describe in what respects their developm ent has been suc-
cessful, and in what respects there are still unsolved problems. In addition, an overview will be presented
of future developm ents that may eventually lead to widespread applications.

Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at San Antonio, San
Antonio, Texas.

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THE CURRENT SITUATION

Since the first studies and experiments with biodegradable osteosyntheses, their development has come
a long way, and a vast knowledge about these materials has been acquired. The vast majority of biodegrad-
able osteosyntheses used today are produced from synthetic semicrystalline poly( a -hydroxy acid) polymers.
Poly(lactide) (PLA) is the material that is most often used, as it is most suitable to produce implants with
acceptable mechanical properties. Poly(glycolid e) (PGA) is another often used material; it degrades faster
and is used primarily in applications where high strength is not the most important factor. Polymer blends
of PLA and PGA are also often used to tailor the properties of a polym er to a specific application. 12,13 Be-
sides PLA, PGA, and PLA/PLG copolym ers, a number of other aliphatic polyesters such as poly(p-diox-
anone) (PDS) and poly( e -caprolactone) (PCL) have also been investigated for use as biodegradable os-
teosyntheses. PDS is used to make pins (Othosorb ® ) and orbital floor implants. 14,15 However, PDS and PCL
are primarily used for the production of biodegradable sutures such as Monocryl ® , a PCL/PGA monofila-
ment suture, and in PDS monofilam ent suture.
At the present time, there are a number of aspects where biodegradable osteosyntheses perform rather
satisfactorily. In other aspects, however, considerable problem s are encountered that stand in the way of
their general clinical use.

The successful areas

Mechanical Properties: The first challenge in the development of biodegradable osteosynthe ses was to
make their mechanical properties match or at least approach those of metal implants. Until the mid 1980s,
the production techniques were not always adequate and, consequently, the obtained osteosynthe ses often
had weak or unpredictable mechanical properties that rendered them unreliable. 11,16– 19 From about 1985
onwards, increased knowledge and improved production techniques made it possible to produce biodegrad-
able osteosynthe ses with sufficient strength and strength retention to provide adequate, sustained, fixation
of low to medium load-bearing fractures.20– 27 Currently, biodegradable implants are produced in the form
of pins and rods (Biofix ® ), interference screws (Bioscrew ® , Phusiline ® ), and plate/screw systems (Lac-
toSorb ® , Bionx ® ). These devices find their application mainly in orthopedic surgery and podiatry for fixa-
tion of epiphyseal and metaphyseal (malleolar, elbow) fractures, in maxillofacial surgery for repair of fa-
cial fractures,28– 31 and for fixation of osteotomies.32,33 However, the mechanical properties of biodegradable
materials are not yet equal to those of metal ones. As a consequence, the lack in strength and rigidity of
biodegradable implants has to be compensated by the use of larger, bulkier designs compared to metal ones.
Production Techniques: Biodegradable polymer devices are produced using compression molding, in-
jection molding, or extrusion techniques. Sometimes, implants are machined from polym er blocks. An ex-
ample of a more elaborate production technique is the so-called self-reinforcement (SR) technique, where
polym er filaments are sintered together to obtain pins and rods with excellent mechanical properties. This
technique has been used for PLA, PG, and PLA/PGA pins and rods, all of which have been marketed un-
der the Biofix ® brandname.21,27
Sterilization Methods: Sterility is a requirement for all surgical implants; biodegradable osteosyntheses
are no exception. Sterilization techniques may cause changes in biodegradable polym ers, and thereby de-
teriorate the mechanical properties and alter their degradation characteristics. Poly( a -hydroxy acid) poly-
mers are thermo-and moisture-labile and degrade mainly by hydrolysis of their ester bonds. 34,35 This ex-
cludes conventional steam sterilization, 36 which features temperatures over 100°C combined with a high
humidity. Therefore, the sterilization method of choice is either ethylene-oxide gas (ETO) -sterilization, or
gamma-irradiation, although these too have certain drawbacks. ETO sterilization is performed at approxi-
mately 50°C but, to be effective, requires a precondition ing phase at a relatively high humidity, which may
cause degradation. An additional concern about ETO sterilization is that gas residues with toxic or even
carcinogenic potential may be left in the sterilized polymer. 37,38 However, with proper aeration, these
residues can be practically eliminated.39,40 Gamma irradiation can induce very pronounced structural changes
in polymers, which may seriously affect the polymers’ material properties and degradation characteris-
tics.41,42 At present, most PLA, PLG, and PLA/PLG osteosynthe ses are sterilized using ETO. With proper
operating conditions, adverse effects on a polymers properties can be kept relatively small. Nevertheless,

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new sterilization techniques that may be more suitable for biodegradable osteosynthe ses are under investi-
gation. These will be discussed later in this paper.

The problem area

Biocompatibility: The main problem area in the developm ent of biodegradable osteosyntheses is the is-
sue of biocom patibility. This has turned out to be a very challenging issue. There are many aspects to the
biocompatibility of biodegrada ble osteosynthe ses, where the dynam ics of a degrading polym er implant, and
those of the surrounding tissue, present a complicated system that still poses a number of yet to be clari-
fied problem s.
For a long time, the biocompatibility of biodegradable PLA and PGA polym ers has been considered to
be beyond reproach. Degradation of these polym ers occurs primarily by hydrolysis 34,35 ; enzymatic activity
is thought to play a contributing role in the later stages of degradation. 43– 46 Free radicals, in particular hy-
droxyl radicals (OH ? ), also appear to play a role in the degradation process.47 The end products of degra-
dation of PLA and PGA, lactic acid and glycolic acid, are hypothesized to be eliminated from the body as
carbon dioxide and water, and an additionally small portion by excretion in the urine and feces.10,48– 50
Early studies of the biocom patibility and toxicity of PLA and PGA predominantly involved animal im-
plantation studies. These generally showed good tissue tolerance toward devices made from PLA, PG, or
PLA/PGA copolym ers, with little or no detectable toxic effects. Reactions to the implants were limited to
mild transient inflammatory reactions.11,16,48 –52 Encouraged by these findings, and with the concomitant
improvement of the mechanical properties, experimental clinical application of mainly PLA- and PGA-
based biodegradable osteosynthe ses began around 1985. The majority of the implants used were pins and
rods that later were marketed under the brandname Biofix ® . 21,26,53 Other implants that were tested include
plate/screw systems for the repair of zygom atic fractures, repair of skull defects in children, and for the re-
pair of orbital floor defects.24,54– 56 Initially, these implants appeared to be quite successful and good tissue
tolerance towards the implants was reported in these studies. Although in some cases secondary fracture
dislocations occurred, this was attributed to insufficient mechanical strength retention of the implants. 53
Unfortunately, in 1989 the first reports about complications associated with the clinical use of biodegrad-
able osteosynthe ses appeared. Since then, the number of reported complications has steadily grown. Thus
far, the list includes swelling, sterile sinus formation, synovial inflammation, bone resorption, and foreign
body reactions at the implantation site.53,54,57 –61 In some cases, osteoarthritis developed. 62 Most of these
complications occurred in the later stages of implant degradation. Sometimes, they were observed years af-
ter implantation.59 In total, complication rates ranging from 7 to 40% were reported in the literature.54,63– 65
This made it clear that a more cautious approach to implantation of these materials was in order, while the
cause of the observed complications should be determined.
Recent in vitro and in vivo biocompatibility and toxicity studies of PLA and PGA have indicated that these
polym ers themselves are not toxic and unlikely to cause adverse tissue reactions.66– 70 It is now suggested
that adverse reactions to poly( a -hydroxy) acid polymers can be attributed to physiological changes in the
tissue surrounding the implant caused by the implant degradation process. The main mechanism of degra-
dation of poly( a -hydroxy) acid polymers is bulk erosion by hydrolysis of ester bonds in the polym er back-
bone. 34,35,71– 74 Due to the degradation process, the physical properties of the polym er will continuously
change. Water penetrates the typically partly crystalline polymer structure and the amorphous zones are hy-
drolyzed. 74– 76 Residual monomer may leach out, as well as chemical residuals from sterilization (e.g., ETO)
and other additives. The crystallinity of the polymer will subsequently increase, partly because of loss of the
amorphous zones, and partly due to recrystallization of low-molecular-weight oligom ers generated by this
process.75 The molecular weight of the polymer will decrease, and a shift occurs in molecular weight dis-
tribution (polydispersity) . While the crystallinity increases, the polymer becomes more resistant to hydroly-
sis, and material changes will proceed at a slower rate. Eventually, the polymer will lose its mechanical prop-
erties and integrity, and will disintegrate. The specific order of events and the timescale along which they
take place depends largely on the specifics of the polymer. For poly( a -hydroxy) acid implants, the degra-
dation time will generally be longer when the initial mechanical properties are better. The mechanical prop-
erties in turn are strongly dependent on the molecular weight. 16,71,76– 81 The degradation process will induce
physiological changes in the tissue surrounding the implant, such as a drop in pH and changes in osmotic

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pressure. 82 When the implant disintegrates, numerous microscopic, highly crystalline, fragments and parti-
cles are released into the surrounding tissue. It has been estimated that this crystalline debris may take more
than 10 years to fully degrade and, therefore, the potential for adverse sequelae may remain present indefi-
nitely. 83,83 Particulation and fragmentation have also been implicated as possible causes for tumorigenesis.85
The recent biocompatibility and toxicity studies mentioned earlier indicate that a drop in pH and change
in osmotic pressure are implicated as most likely causes of any observed toxic response.66– 70 Macrophages
in particular are damanged, and fibroblasts are damaged to a much lesser extent. 86 In addition, toxic effects
are directly related to the amount of polymer particles introduced in the in vitro systems with evidence of
direct interaction with osteoblasts, affecting the bone remodeling process. 67,87
A simplified explanation for the observed adverse reactions is that high particle loads in the tissue over-
whelm the cleaning capacity of macrophages phagocytosin g the particles, which leads to cell damage, ly-
sis, and death. The pH and osmolarity changes even further hamper the normal function of the hosts’ de-
fense mechanism. Eventually, these events may lead to one or more of the clinically observed complications.
The actual onset of an increased tissue reaction may be triggered by the time the molecular weight of a
biodegradable implant has decreased to approxim ately 5,000–6,000, at which point the solubility of PLA
and PLA/PLG polym ers significantly increases.88,89
It is important to realize that, besides the specific polym er properties, other factors can influence the pos-
sible occurrence and the severity of any adverse reaction. Some of these are related to the implant, such as
size and geometry of the implant, surface texture,90 presence of additives, 91 and mechanical stress. Others
are related to the specific application, such as the implantation site, tissue-clearing capacity, and age of the
recipient.92–95 In vitro toxicity assays are generally not suitable for the detection of acute or chronic in-
flammatory foreign body reactions 96 and, therefore, in vivo testing and evaluation of biodegradable poly( a -
hydroxy acid) implants will remain necessary to evaluate certain aspects of an implant’s biocompatibility.

FUTURE PERSPECTIVES

Biocompatibility
Great effort is being made to solve the problems regarding the biocompatibility of biodegradable poly-
mers. These efforts are aimed at many different aspects, including the effects of additives, polymer struc-
ture and morphology, and tissue interaction with particulate material.
Implant Additives: To prevent the adverse effects of low pH around biodegradable PLA and PLG im-
plants, studies are being conducted to examine whether these can be prevented by the incorporation of ba-
sic salts within the implant. During in vitro tests, this technique was able to stabilize the pH during the en-
tire degradation process without affecting the degradation dynam ics of the implants. 97
To prevent adverse interference with ossification around biodegradable implants, PLA/PLG implants
loaded with recombinant human fibroblast growth factor-2 (rhFGF-2) are being evaluated. Compared to
nonloaded samples, rhFGF-2 loading was effective in overcoming retarding effects on ossification. It was
noted, however, that degradation might be influenced by the incorporation of rhFGF-2 in polymer im-
plants. 98 Similar experiments are conducted with incorporation of transforming growth factor- b (TGF- b )
in SR-PLA pins. When using these pins, bone healing in rats was enhanced compared to untreated implants.
This effect, however, appeared to be due mainly to faster callus formation and overall bone healing was
not accelerated.99 Another variation that is studied is the soaking of implants with monoclonal antibodies
to interferon- g (IFN- g ) to inhibit the function of macrophages and giant cells. The results clearly demon-
strated the importance of IFN- g in inflammatory reactions to biomaterials, and that IFN- g antibodies from
soaked implants were effective in delaying the activation of macrophages and foreign body giant cells.100
Although this latter study was conducted with dermal sheep collagen implants, it seems reasonable to as-
sume that this may also apply to biodegradable polymer implants. Finally, an interesting technique with re-
gard to implant additives is the use of ultrasound. Ultrasound could be used to manipulate drug release ki-
netics from biodegradable PLA/PLG carriers without surgical intervention. Studies in vitro showed that
ultrasound can significantly increase protein elution from PLA/PLG specimens, either by increasing the dif-
fusion rate of a drug from a polym er, or increasing the degradation of the polym er by mechanochemistry.101

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Polymer Structure and Morphology : Modifications in polymer structure and morphology are aimed at
preventing sudden acid release and particle overload in the surrounding tissues. An alternative method to
diminish acidic conditions, i.e., a pH drop around degrading implants, is to adjust the initial molecular
weight distribution (polydispersity) of the polym er. The feasibility of this method for modulating lactic
and/or glycolic acid release was demonstrated in vitro. The release rate of lactic acid increased for PLA
membranes as the percentage of low-molecular-weight component in the polym er blend increased.102 Other
studies are aimed at modifying the polym er degradation dynamics by the incorporation of metal salts. Re-
sults showed that such modification is possible over a wide range. 103
Another aspect being examined is the influence of polym erization initiators. The degradation character-
istics of PLA/PLG polymers initiated by either stannous-octoate or zinc showed marked differences for
fairly large parallel-sided specimens.104 To circumvent the effects of polymer disintegration resulting in
high particle loads in the surrounding tissues and sudden changes in conditions such as pH and osmolarity,
the possibilities of creating polymers that degrade by surface-erosion rather than bulk-erosion are being ex-
amined. To achieve surface erosion in polymers like PLA and PGA, it is very important to prevent water
penetration into the polymer. This requires the elimination of microvoids in the polymer, and the preven-
tion of microcracks during degradation. To achieve this, techniques like orientation by hot drawing or high-
pressure annealing of amorphous poly(lactide)s may prove useful.84 Another method to achieve increased
surface erosion may be the creation of crosslinks between the lamellae in the PLA polym ers structure with
1% spiro-bis-dimetylene-carbonate. 105 Compared to non-crosslinked PLA, such polymers show less swelling
and yield less and smaller crystalline degradation debris.83
The reduction of a polym er’s crystallinity facilitates hydrolysis, which may in turn facilitate in vivo degra-
dation. This was demonstrated for PLA, where the introduction of 4% D -lactide units in poly( L -lactide) to
distrub the crystallinity produced enhanced degradation rates, and smaller amounts of crystalline debris of
smaller size than from poly( L -lactide). 55,83 However, even initially noncrystalline PLA and PLG polym ers
may still partly recrystallize during degradation.106
Particulate/Tissue Interaction: A number of studies are being conducted to understand better the tissue
interactions with particulate debris from biodegradable polym ers. This may lead to methods that prevent
the occurrence of adverse effects. As mentioned earlier, it was found that toxic effects appear to be in part
related to the amount of polymer particles introduced in in vitro systems.87 This may be due to the irre-
versible inactivation of certain enzymes when they become bound to biodegradable polym er particles.107
Furthermore, the production of reactive oxygen species (free radicals) by macrophages, a major mechanism
by which inflammatory cells respond to foreign materials, may be strongly increased in the presence of pro-
tein-coated particles. 108 Rapid degradation techniques at elevated temperatures have been developed to study
the degradation characteristics of polymers in reduced amounts of time.109,110 Such techniques also give
the opportunity to study the morphology of particles generated by degradation, and to retrieve particles111
for use in in vitro assays and in vitro implantation studies.

Sterilization methods
Most of the currently employed sterilization techniques for biodegradable PLA and PLG osteosyntheses
adversely affect their physical and mechanical properties. This is strongly related to the fact that these ma-
terials are heat and moisture labile. Consequently, new methods are frequently aimed at either limiting the
exposure of implants to be sterilized to high heat, moisture, or both. This may be accomplished by modi-
fication of existing methods, or by the development of new procedures.
Heat treatment is one of the methods that is examined for sterilization of biodegradable polym ers. This
process takes place in a relatively dry atmosphere of an inert gas or vacuum, and at a temperature that is
considerably lower than that used for common dry sterilization procedures, which can be as high as 190°C.
When biodegradable injection-molded pins were subjected to heat of 105°C to 150°C under vacuum and/or
argon for 1 to 50 h, all samples were found to be sterile after 1 h at 135°C. 112 However, this method did
result in notable changes in the mechanical properties, molecular weight, and crystallinity of the samples,
which may well influence their clinical performance.
The sterilizing effects of low-temperature plasma treatment of various PLA polymers are being studied.
Treatment of samples with oxygen or carbon dioxide plasma for 15 and 30 min at 100 Watts yielded com-

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plete sterility. 113 Under similar conditions, nitrogen or argon plasma were only 70% effective. More im-
portantly, however, there were no changes in the mechanical properties of the treated implants, and only
minor changes were noted for molecular weight and crystallinity. 113 This method, therefore, appears to be
very promising.
An example of modification of an existing method is a special steam sterilization process that was de-
veloped by Rozema et al.36 Although the actual sterilization temperature employed equals that of regular
steam sterilization, the duration of the cycle is much shorter, and exposure to moisture is kept to a mini-
mum by very carefully controlled cycle steps. This cycle demonstrated to be effective at obtaining sterility
for contaminants less than 10 4 microorganism s per gram based on the IMO-concept, 114 a mathematical
model used to compare the efficacies of sterilization cycles to the efficacies of the cycles in the European
Pharmacopoeia. There was a significant loss in molecular weight of the sterilized samples, but the effects
on the mechanical properties were only minimal.36
One very elegant method for sterilization of biodegradable poly( a -hydroxy acid) osteosyntheses is au-
tosterilization by injection molding. The attractiveness of this method is that it is intrinsic to the implant
production process. Injection molding of poly( DL -lactic acid) and poly( L -lactic acid) granules, contaminated
with thermoresistant spores of Bacillus stearothermophilus, led to a reduction of 99.99% of viable spores
in the produced samples.115 For these experiments, heavily contaminated (. 10 5 spores/gram) raw material
was used and, although not completely effective, the results are very encouraging. It appears likely that for
less heavily contaminated raw material produced under strictly controlled conditions, total effectiveness
may be achieved.

Mechanical properties
The mechanical properties of PLA and PGA osteosyntheses are still inferior to those of their metal coun-
terparts. Currently, reliable, sustained fixation is only possible for less-demanding applications. However,
if biodegradable osteosynthe ses are to be used for more demanding fracture fixation, stronger materials will
be needed. The most important consideration for the developm ent of stronger materials is to keep the di-
mensions of biodegrada ble implants within acceptable limits. The whole purpose of using biodegradable
implants is their capacity to degrade eventually. To facilitate innocuous implant degradation, it is impor-
tant to introduce as little material as possible into the patient. Reducing the size of a biodegradable implant
will, if everything else stays equal, always be beneficial to its biocompatibility.
Several efforts to improve mechanical properties of biodegradable implants are aimed at obtaining a high
degree of fibrillar or molecular orientation. The SR-technique is an early example of a technique applied
to biodegradable polym ers to obtain fibrillar orientation. The benefit of the technique is that very good val-
ues are obtained for bending and shear strength of the produced rods and pins. 27 Another way to obtain fib-
rillar orientation for biodegradable devices is solid-state extrusion as was shown by Weiler et al. 116 Solid-
state extrusion is a technique where polymer objects are produced by forcing solid polym er through a heated
metallic block and die. In conventional extrusion, the polym er is preheated to above its glass-transition tem-
perature. This is the temperature at which the polymer changes from its solid to a rubbery state, or vice
versa. Solid-state extruded PLA rods were found to have greatly improved bending modulus and bending
and shear strength compared to similar, conventiona l melt-extruded rods.116 This improvement is ascribed
to a highly oriented, fibrillated morphology of the produced samples. The effects of manipulation of mol-
ecular orientation in a polym er were explored by Burg et al.117 A so-called solid state uniaxial orientation
(SS-UO) process was used to orient two types of lactide polym er films. Measurement of flexural modulus
after degradation of the films in phosphate-bu ffered solution showed that, although orientation did not have
an overall significant effect on the flexural modulus, there was a significant material/orientation interaction.
A specific problem concerning the mechanical properties of biodegradable, semicrystalline, and amor-
phous PLA and PGA polym ers is that they are brittle under tensile and bending loads. For application as a
fixation device, this is a major shortcom ing. Blending of these polymers with biodegradable rubbers may
offer a solution to this problem . With incorporation of a poly( L -lactide-co- e -caprolactone) rubber, the im-
pact strengths of semicrystalline PLA copolymers could be dramatically increased. Crystallinity of the PLA
matrix had a pronounced positive effect on the toughness attained at a certain rubber level. Similar results
were found with incorporation of a poly(trim ethylene carbonate-co- e -caprolactone) rubber with PLA/PGA
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blends, whereas the amount of glycolide incorporated had a negligible effect on the impact properties. 118,119
Rubber toughening as described above does normally result in a decrease of the tensile strength and bend-
ing modulus of the polym er. However, in a dog study, fixation of mandibular fractures with rubber-tough-
ened PLA plates and screws showed uneventful fracture healing and good tissue compatibility up to 45
weeks after implantation. 120

EPILOGUE

The foregoing discussion describes the complexity underlying developm ent of truly biocom patible, me-
chanically strong biodegrada ble polym er osteosynthe ses. Inherent to its nature, a change in one of the ini-
tial properties of a biodegradable polym er will always affect most, if not all, other properties, and thus the
subsequent clinical performance. Whether it is a polymer additive, a change in the polym er structure and
morphology or sterilization procedure, every change may have far-reaching consequences for the mechan-
ical performance and biocom patibility of the produced implant. In addition to this, the polymer implant has
to function in the human body, a system that also is highly dynam ic. Fixation of a fracture or defect with
a biodegradable osteosyntheses brings two continuously changing systems together.
The problem s of biocom patibility are certainly not all severe; however, one must reckon with the possi-
bilities for the development of unforeseen complications that may occur even a very long time after im-
plantation of a biodegradable material. One such problem may be the reported migration of particles from
PLA implants to efferent lymph nodes. 121 For biodegrada ble polym er implants to gain a more widespread
acceptance and use, the biocom patibility problem s have to be unequivocally solved. In addition, still bet-
ter mechanical properties are needed to make biodegradable implants more competitive with metallic im-
plants, and to extend their possible use to larger fractures and defects. Finally, their acceptance and use may
depend on the treatment conventions and protocols that are observed, and that may show global differences.
For example, in many European countries metallic implants are routinely removed, whereas in the United
States this is less common practice, thereby partly surpassing the advantage of biodegradable implants that
a removal operation is not necessary. Presently, the application of biodegradable polym ers in large implants
for the fixation of large fractures or defects should not be encouraged.

ACKNOWLEDGMENT

This work was supported by NIH/NIDCR grant DE 12542-01A 1.

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Address reprint requests to:

John P. Schmitz, D.D.S., Ph.D.
Department of Oral and Maxillofacial Surgery
The University of Texas Health Science Center at San Antonio
7703 Floyd Curl Drive
San Antonio, TX 78284

E-mail: schmitz@uthscasa.edu

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