Degradation rates of polymers and

copolymersof polylactic and

polyglycolic acids
Duane E. Cutright, Colonel, DC, USA,* Bienvenido Perez,
Lieutenant Colonel, DC, USA,** Joe D. Beasley, III, Major,
DC, USA,*** Wayne J. Larson, Lieutenant Colonel, DC, USA,**** and
Wil1ia.m R. Posey, Lieutellant Colonel, DC, USA*****
UNITED STATES ARMY INSTITTJTE OF DENTAL RESEARCH, WALTER REED ARMY
MEDICAL CENTER, WASHINGTON, D. C.

S everal researchers have shown that the tissue reaction to polylactic acid
(PLA) and polyglycolic acid (PGA) is minimal. These same studies have shown
that these polymers are biodegradable and replaced by conned&e tissue and/or
bone.
Numerous studies at this institute have shown that PLA and PGA are
acceptable in various forms for fracture fixation and soft-tissue approximation.
Cutright and Hunsuck’ repaired orbital blow-out fractures in monkeys with
PLA sheets and repaired mandibular symphysis fractures in monkeys with
multiple strands of PLA sutures. 2 A comparative study of PLA and PGA was
done by Cutright and co-workers. S Hunsuck and Cutright* used pins of PLA
for mandibular fixation in clogs. Getter and Cutright used a combination of
plates and screws for mandibular fracture fixation. All of the above-mentioned
studies showed good tissue receptivity, with-slow resorption, attended by varying
numbers of phagocytic cells and without an inflammatory reaction after the
initial wound had healed. The disappearance of these materials has been variable
according to the size, shape, and type of material used. The PGA sutures have

*Chief, Division of Oral Pathology.

**Chief, Department of Clinical Oral Pathology, and Assistant Chief, Division of Oral
Pathology.
***Chief, Experimental Pathology Section, Division of Oral Pathology.
****Division of Ord Pathology.
‘*‘**Former Staff Member, Division of Oral Pathology.

142
Volume 37 Polymers and copolymers of PLA and PGA 143
Number 1

been shown to disappear as early as 50 days,6 whereas the large PLA pins were
still not completely degraded at 12 months.4 This has been verified by C,, studies
by Brady and associates.7
A complete review of PGA and its properties has been reported by Frazza
and Schmitt,6 who showed disappearance rates from the implant site of 99 per
cent at 4 months. It was also shown histologically that the PGA sutures have
disappeared by 50 days. However, work by Cutright and co-workers3 has shown
longer times, up to 120 days, before resorption is complete.
Studies on the physical characteristics of both PLA and PGA have been
published by Frazza and Schmitt6 and Kulkarni and associates.* Their labora-
tory findings have shown that these materials have sufficient initial strength to
be used for fracture fixation in various forms, i.e., pins, plates, sutures, and
sheets.
Ideally, fractures of the jaws should remain fixed for between 4 and 8 weeks,
with longer times being required occasionally. Also ideally, the fixation device
should be biodegradable, with as little tissue reaction as possible, thereby
obviating the need of a second operation for removal of the device. PGA and
PLA are both tissue degradable, but over periods of time are not satisfactory for
jaw fixation. Therefore, we intended in this experiment to attempt to find a
polymer or copolymer of PLA and PGA which would sufficiently fix the bone
fragments for 4 to 10 weeks and yet disappear rapidly after the bone was
satisfactorily healed.

METHODS AND MATERIALS

Five different polymers and copolymers of PLA and PGA were prepared by
Battelle Columbus Laboratories, Columbus, Ohio. The different compositions
were 100 per cent PLA, 75 per cent PLA to 25 per cent PGA, 50 per cent PLA
to 50 per cent PGA, 25 per cent PLA to 75 per cent PGA, and 100 per cent
PGA. From each of the five different compositions, 100 cylindrical pellets that
measured approximately 1,600 by 1,750 microns were made. The physical proper-
ties will be given in another paper that is to be published. In addition to the five
compositions, we found that slow cooling and fast cooling produced different
crystal formations in the 100 per cent PLA and the 100 per cent PGA. These were
then included in the experiment as part (one half) of the 100 per cent PGA and
PLA groups. Two hundred and seventy-five male white albino rats were used for
this experiment. They were anesthetized with pentobarbital, and both hind legs
were clipped. An incision, 1 cm. in length, was made on the anteromedial surface
of each leg so as to expose the upper metaphyseal area of the femur. A No. 6 round
dental bur was used to bore through the cortex into the medullary spaces of both
legs. Pellets of the same composition were placed in both legs, except for the
100 per cent PLA and 100 per cent PGA. Animals of these two groups had slow-
cooled pellets placed in the left leg, and fast-cooled ones in the right leg. The
wounds were then tightly sutured, and the animals were returned to marked
cages. The duration of the experiment was 220 days, with harvesting of samples
every 20 days. Five animals were killed at each time period, which gave ten
samples per time period of each material, except the 100 per cent PLA and 100
144 Cubight et al. Oral Rurg.
January, 1974

Table I. Perccntagr of tlcgraclation (computed)

100
r
t=j 100% PGA

CXZ 100% PLA

I 50% P LA.

- 25% P.LA

IO

20. 40 60 80 I 180 200

TIME IN DAYS

per cent PGA, for which there were five fast-cooled pellets and five slow-cooled
pellets in each group.
When the animals were killed, the complete femur was removed, carefully
cleaned of soft tissue, and fixetl in buffc~d formalin. These were then decalcified,
grossed in the same plane, ant1 preparcci by sectionin, 0’ at 6 microns ant1 stained
with hcmatox~lin and eosin.
Material for slides from each of four sites was taken in step serial fashion.
On the slides, each pellet or space previously occupied by the pellet was
measured in two directions, i.e., height and breadth, using a microscopic microm-
cter attachment. The average figure obtainetl by means of t,he micrometer was
compared to the known original size, and a percentage figure of the decrease in
size (degradation) was t,hus obtainetl.

FINDINGS

For all degradation rates, WC Table I.

The number of samples retrieved varied from a low of four for 50 per cent
PIA at 100 days to a high of ten in many instances, with an average retrieval
of 7.85 samples for each material at each time period.

100 per cent PLA

The PlA pellets dissolved a\va,v in processing. So inflammation was present

at any time period. As early as 20 days, the pellets were all surrounded by a thin
ring of bone. The bone was against the pellet, with areas of marrow occasionally
between the pellet and the bone. The slow-cooled and fast-cooled samples showed
no differences at any period. The bony capsule gradually thickened with time
(Fig. 1R). Rcmodelling of this bony capsule was evident at 80 days, with many
basophilic resting and reversal lines. The size of the pellet remained nearly
stationary until 120 claim, when it measured 1,540 microns (Table I). h’o eri-
Volume 37 Polymers and copolymers of PLA and PGA 145
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Fig. IA. 100 Per cent polylactic acid at 40 days. (Magnification, x30.) The thin ring of
bone completely encircles the space occupied by the pellet. The bone and marrow surrounding
the pellet have a normal appearance histologically. No inflammatory cells are present.
Fig. 1B. 75 Per cent polylactic acid at 40 days. (Magnification, x30.) Very small fibers of
connective tissue can be seen in the pellet. Bone completely encircles the pellet, and the
surrounding tissues have a normal appearance.
Fig. 1C. 50 Per cent polylactic acid at 40 days. (Magnification, x33.) Just inside of the
bony ring can be seen many foam cells. Some can even be seen deep within the pellet.

Fig. 1D. 25 Per cent polylactic acid at 40 days. (Magnification, x33.) Much of the pellet
has degraded and it is surrounded by a thick ring of foam cells.
Fig. 1E. 100 Per cent polyglycolic acid at 40 days. (Magnification, x30.) The pellet is
completely encircled by bone. The surrounding bone and marrow have a normal appearance
histologically.
146 Cutright et al. Oral Surg.
January, 1974

Fig. bA. 75 Per cent polylactic acid at 80 days. (Magnification, x33.) Bone, marrow cells,
and connective tissue surround the pellet. Small, round, ragged areas of degradation can he
seen throughout the pellet.
Fig. BR. 50 Per cent polylactic acid at 80 days. (Magnification, x30.) The pellet has
softened and is surrounded hy hone. Connective tissue has been formed around much of the
pellet.
Fig. 2X. 75 Per cent polylactic acid at 80 days. (Magnification, x45.) The center portion
of the pellet shows hrightly colored birrfringent spots. The pellet has softened and :I wide
ring of phagocytic foam cells surrounds it. Small bone spicules are developing within the
foam cells.

dence of degradation was found until the appearance of a few foam cells at 100
days. The foam cells were never a prominent part of the degrading process with
100 per cent PTJA, but were occasionally present after 100 days. The only con-
sistent evidence of degradation was the slow general decrease in size of the
pellets to 955 microns at 220 days (Fig. 3A). At 220 days, the bony capsule
was slightly thicker but had maintained a rather uniform thickness even with
the decrease in pellet size. The marrow and a few connective tissue fibers were
still present between the bony ring and the pellet (Fig. 5A).

75 per cent PLA

No inflammatory cells were present at any time period. The 75 per cent PLA
dissolved during processing, leaving only the outline of the area in the tissue.
Phagocytic cells present as foam cells were prominent at 40 days, some of which
could be found in the marrow at some distance from the pellet (Fig. 1B). The
pellets showed the same capsule of bone and connective tissue as had the other
types of materials throughout the experiment. At 60 days, the pellets had a
homogeneously eosinophilic appearance, which indicated liquefaction. Also, con-
nective tissue and bone spicules were present within the pellet. The degradation
pattern showed many small, jagged, irregular, round areas at 80 days (Fig.
2A). Only occasionally did particles of the 75 per cent PLA polarize. The 100-
day samples showed a ring of foam cells, connective tissue, and a bony capsule.
The average size of the pellets had decreased to 1,332 microns. At 120 days, the
Volume 37 Polymers and copolymers of PLA and PGA 147
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Fig. 3A. 100 Per cent polylactic acid at 120 days. (Magnification, x48.) Pellet is encircled
with bone and marrow cells. No histologic evidence of resorption is present.
Fig. SB. 75 Per cent polylactie acid at 120 days. (Magnification, x48.) The bony ring has
thickened. The pellet shows oval areas of resorption and is nearly replaced by foam cells.
Fig. 3C. 50 Per cent polylactic acid at 120 days. (Magnification, x48.) The pellet has been
entirely degraded and replaced by bone, foam cells, and marrow cells. Remodelling and reorien-
tation of the bony trabeculae has occurred.

Fig. 30. 25 Per cent polylactic acid at 120 days. (Magnification, x48.) Bony ring has
thickened and the pellet has been replaced by foam cells.
Fig. S’E. 100 Per cent polyglycolic acid at 120 days. (Magnification, x48.) The bony ring
is thin, and a thin layer of connective tissue lies between it and the pellet. Degradation is
minimal.
148 Cutright et al. Oral Surg.
January, 1974

Piy. 4. 75 Per cent polylactic acid at 140 days. (Magnification, x48.) The bony encapsula-
tion is prolifeFating into the pellet. The remaining pellet shows areas of degradation and many
foam cells.

pellets showed the peculiar round areas of degradation throughout the pellet.
These circles had very jagged edges. The pellet material was homogeneous and
eosinophilic (Fig. 3B). The pellets were surrounded with a ring of foam cells
and an outer ring of bone. Five of the samples showed bone within the pellet. By
140 days, the ring of foam cells and bone had become much thicker and showed
trabeculae growing into the pellet (Fig. 4). The average size of the pellet that
remained was 823 microns. The degradation via the phagocytic foam cells con-
tinued, and at 180 days, only small pieces of four pellets remained. Their average
size was 20 microns. At 200 days, only particles of one pellet were found. The
final time period of 220 days showed no pellets remaining, but foam cells could
be demonstrated in the marrow in one animal (Fig. 5B).

50 per cent PLA

Much of the pellet dissolved during the processing. The birefringence was
spotty. Foam cells were common at 40 days (Fig. 1C). By 60 days, the pellet
was completely surrounded by a ring of foam cells. One sample showed bone
already developing within the pellet. The average size of the pellet that remained
was 776 microns (Table I). The 80-day samples showed extensive breakdown of
the pellet (Fig. 2B). The N-day samples showed extensive infiltration of the
pellet with connective tissue and bone. There were many phagocytie cells, and
the average diameter of the pellets that remained was 658 microns. By 120 days,
the pellets had essentially disappeared (Fig. 3C), although small particles
remained until 160 days. At 180 days, no pellets were present, and only the
reorientation and remodelling of the cortical plate gave evidence that any pellets
had been placed.
Volume 37 Polymers and copolymers of PLA and PGA 149
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Pig. 58. 100 Per cent polylactic acid at 220 days. (Magnification, x48.) The hone en-
circling the pellet shows thickening.
Fig. 5B. 75 Per cent polylactic acid at 220 days. (Magnification, x48.) The only evidence
of the pellet is the small clump of foam cells (left center).
Fig. 5C. 100 Per cent polyglycolic acid. (Magnification, x48.) Very little evidence of
resorption is present.

25 per cent PLA

No inflammatory cells were present. The 25 per cent PLA did not dissolve
during fixation and showed spotty birefringence throughout the pellet.
The 20-day samples were ringed by bone and a small amount of connective
tissue between the bone and pellet and showed red marrow against the pellet in
a few areas. The first evidence of degradation was found at 40 days and showed
the growth of capillary buds and connective tissue into the margins of the pellet
(Fig. 1D). The pellets had decreased in size to an average of 1,320 microns at
40 days. It was possible to identify two different particles in the pellets: one was
clear and polarized, and the other was more eosinophilic and did not polarize. By
60 days, the pellets were homogeneously eosinophilic, which indicated liquefac-
tion. A thick layer of foam cells surrounded the pellet just inside the bony capsule.
The 80-day samples showed increased numbers of foam cells and some granu-
lation inside the bony encapsulation. Within this deeper layer, new bone
trabeculae formed an incomplete second ring of bone. Other samples showed
scattered trabeculae of bone within the pellet area (Fig. 2C). We estimated the
average amount of degradation to be 20 per cent. The average size of the pellet
that remained was 1,140 microns. In some samples, the pellets had been com-
pletely replaced with foam cells and bone trabeculae at 100 days. The average
size of the pellets that remained was 400 microns. By 120 days, the average
amount of degradation was 95 per cent, and only traces of the pellets remained.
In some samples, foam cells could still be seen among the remodelling trabeculae
(Fig. 30). At 140 days, evidence of two pellets could be found, and each
measured less than 100 microns. The last evidence of 25 per cent PLA was
found at 160 days and consisted only of remodelling of the cortical bone.
150 Cutright et al. Oral Burg.
January, 1974

100 per cent PGA

No inflammatory cells were present in any sample at any time period. The
pellets were surrounded by bone, marrow, and connective tissue. Little histologic
change occurred during the first 140 days (Figs. 1E and 3E). By 160 days,
extensions of connective tissue could be seen penetrating into the pellet margins.
A few foam cells were present, and the bony capsule was thickened. The average
size of the pellet that remained was 1,400 microns. The last time period tested,
220 days, showed only the increased thickness of the bony capsule, a few exten-
sions of fibrous connective tissue into the pellet margins, and a decrease in
average pellet size to 1,345 microns (Fig. 5C).

DISCUSSION
Throughout the experiment there was never any evidence of inflammatory
cells as a reaction to the copolymers, thus substantiating our previous reports
of the excellent tissue tolerance to these materials. This quality was also demon-
strated by all the polymers and copolymers in the early samples (20 days) by
the growth of bone directly against the pellet. Where there was no bone, new
and active marrow lay directly against the pellet. Only the 100 per cent PGA
regularly showed a thin layer of connective tissue between the bone and the
pellet.
The birefringent quality of the PGA could be detected with a polarizing
attachment on the microscope. The amount of birefringence appeared to be
directly proportional to the amount of PGA present. The small birefringent dots
in the 25 per cent PGA copolymer appeared to be nearly homogeneous in the
100 per cent PGA polymer.
The rate of disappearance of the polymers and copolymers shown in Table I
represents the average rate and time of disappearance, because all pellets of the
same composition did not disappear simultaneously.
The rate of degradation varied markedly among the various types of pellets
of the same composition. For example, one pellet of 25 per cent PLA had been
completely degraded at 100 days. However, pellets of 25 per cent PLA exhibited
the fastest rate of degradation. The average amount degraded was 77 per cent at
100 days, and reached 98 per cent by 120 days. The second fastest degrading
material was the 50 per cent PLA. These pellets required approximately 20 days
more than the 25 per cent PLA and were essentially 100 per cent degraded by 140
days, although traces remained at 160 days. The third fastest material in rate of
disappearance was the 75 per cent PLA, which showed approximately 98 per
cent resorption by 180 days, with only foam cells and particles of one pellet at
220 days. The 100 per cent PLA was the fourth fastest material to degrade. It
showed degradation only by a decrease in average size of the pellet to 955
microns and a calculated percentage degradation of 43 per cent at 220 days. The
slowest polymer or copolymer to degrade was the 100 per cent PGA; pellets of
this composition showed an average size of 1,395 microns at 220 days, or only
17 per cent degradation. These results agree with our previous findings on PLA
and PGA, and are also in disagreement with published figures for PGA sutures.”
Volume 37 Polymers and copolymers of PLA and PGA 151
Number 1

However, these pellets are not directly comparable to braided sutures. Therefore,
more research is needed in this area.
No significant differences could be found between the fast-cooled and slow-
cooled polymers. This seems to indicate that the different crystal formation did
not affect the body’s ability to degrade the material.
All of the pellets became encapsulated with bone by 20 days. This encapsula-
tion remained throughout the experiment and thickened and replaced the pellet
as it was resorbed. In the copolymers, which tended to degrade fastest, the bone
would occasionally form a second ring, with many trabeculae inside the first
ring of bone. This quality of bone establishing itself before the formation of
fibrous connective tissue is an important characteristic of these materials when
used for bone fixation. Similar but slightly slower replacement was described by
Cutright and Hunsuck’ in the floor of the orbit. Bone around and within the
pellet undergoes physiologic resorption and remodelling at an early time.
The resorption of solid plates of PGA was reported by Cutright and
Hunsuckl to occur by the formation of small outgrowths of capillaries into the
plates. The blind buds gradually received nuclei and then became patent. Foam
cells were not found when pure PLA was used. In this study, a similar process
occurred with the 100 per cent PLA and PG,4, but most resorption of the
copolymer pellets was by phagocytic foam cells. However, when the pellet
liquefies, the capillaries appear to penetrate throughout the pellet and cause
small, round, ragged areas of resorption, as was shown in Figs. 6 and 10. No
significance has as yet been attributed to these two methods of resorption. Many
times, the foam cells would form a thick ring around the remaining pellet and
just ahead of the dense connective tissue and bone. When the pellet was being
rapidly removed, these foam cells could be followed for some distance into the
marrow, where they gradually disappeared, leaving no histologic trace of their
further movement. The first appearance of foam cells was in the go-day sample
of the 50-50 copolymer. From this time on, they appeared constantly in the
copolymers, but did not show in the polymers until 110 days, when a phagocytic
foam cell was occasionally present around the 100 per cent PLA.
It had been noted in some samples of PLA in earlier studies that the material
would start to degrade and then would rapidly liquefy. This feature was found
in this study also, especially in the copolymers that degraded the fastest. The
pellet would appear histologically as a homogeneous, granular, eosinophilic
material surrounded by connective tissue. Foam cells and blood vessels would
form around the periphery of the liquefied pellets and rapidly migrate into
them.
As soon as the pellet has been degraded, there is immediate remodelling and
resorption of the bony t,rabeculae within the marrow space occupied by the
pellet. Coincident with the final phagocytie reaction is the regeneration of active
red marrow and the final reorientation and remodelling of the cortical plate.
This study has shown that resorption rates can be altered by varying the
proportions of PLA to PGA, and that these times encompass those periods
required for the fixation of various types of fractures. Remaining, however, is
152 Cutright et al. Oral Surg.
.January, 1974

the question of the strength of these materials at the various postoperative

times. These characteristics are being investigated and will be reported on later.

SUMMARY
This study has substantiated the following previously reported characteristics
of these polymers and copolymers: They are biodegradable. The degradation is
accomplished by capillary ingrowth and/or phagocytic foam cells. The degrada-
tion is not accompanied by inflammation. The pellets are replaced by fibrous
connective tissue and/or bone and marrow tissue. Bone is deposited directly
upon and within these materials, thus providing good continuing stabilization.
Furthermore, this study has established that, by varying the proportions of
PLA to PGA, resorption times can be varied from less than 100 days to periods
in excess of 220 days. These materials degrade in the following order: 25 per
cent PLA degrades first ; .iO per cent PLA degrades second; 75 per cent PLA
degrades third; 100 per cent PLA degrades fourth; 100 per cent PGA degrades
the slowest. The fast-cooled and slow-cooled polymers with different crystal
formations do not affect the degradation rates. The ranges of resorption en-
compass the times require<1 for fracture fixation.
Studies are presently in progress on other proportions of these polymers and
on tlifferent polymers.
REFERENCES
1. Cutright, D. E., and Hunsuck, E. E.: The Repair of Fractures of the Orbital Floor, ORAJ,
SURG. 33: 28-34, 1972.
2. Cutright, D. E., Hunsuck, E. E., and Beasley, J. D., III: Fracture Reduction Using a
Biodegradable Material, Polylactic Acid, J. Oral Surg. 29: 393-397, 1971.
3. Cutriaht. D. E.. Beaslev, J. D., III, and Perez, B.: Histologic Comparison of Polylactic
and Polyglycolie Acid Sutures, ~RAI, &JRG. 32: 165173, 1971. -
Hunsuck, E. E., and Cutright, D. E.: Unpublished data.
t: Getter, L.. and Cutright, D. E.: Fracture Fixat,ion Using Biodegradable Material, J. Oral
Surg. 50: 344-348, 1972.’
6. Frazza, E. J., and Schmitt, E. E.: A New Absorbable Suture, J. Biomed. Mater. Res.
Symposium 1:. 43-58, 1971.
7. Brady, J. M., Cutright, D. E., Miller, R. A., Hunsuck, E. E., and Battistone, G. C.: Resorp-
tion Rate, R,outs of Elimination and Ultrastructure of the Implant Site of Polylactic Acid
in the Abdominal Wall of the Rat, J. Biomed. Mater. Res. 7: 155-166, 1973.
8. Kulkarni, R. K., Moore, S. G., Higyeli, A. F., and Leonard, F.: Biodegradable Polylnctic
Acid Polymers, J. Biomed. Mater. Res. 5: 169, 181-191, 1966.

Reprint requests to :
Colonel Duane E. Cutright
Division of Oral Pathology
U. S. Army Institute of Dental Research
Walter Reed Army Medical Center
Washington, D. C. 20012