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The repair of fractures of the orbital floor using biodegradable polylactic acid
The repair of fractures of the orbital floor using biodegradable polylactic acid D. E. Cutright, E. E. Hunsuck, UNITED
STATES
WALTER
REED
Lieutenant Lieutenant ARMY ARMY
INSTITUTE MEDICAL
Colonel, DC, USA,” and Colonel, DC, TJXA+* OF DENTAL
RESEARCH,
CENTER
In the repair of blowout fractures, resorption of polylactic acid (PLA) was accomplished by a peculiar phagocgtic process involving phagocytic cells, giant ceIIs, and villous projections. PT,A tissue compatibility was found to be very good. Clinically, the function of the eye was normal. This study substantiates previous studies concerning the tolerance of tissues for PLA.
S
ince 1965, there has been an increasing interest in the use of biodegradable materials for suturing, fracture fixation, etc. Those biodegradables which represent normal constituents of the metabolism of lactic acid have shown the most promise. The tissue reaction and disappearance rate of polylaetic acid (PLA) and polyglycolic acid (PGA) have been previously rep0rted.l.* These studies have shown very good tissue compatibility and demonstrated the feasibility of using these polymers in surgery. Both PLA and PGA have been made into sutures. Since 1968, here at the United States Army Institute of Dental Research, we have used PLA in various forms (Fig. 1.) and for different purposes (Figs. 1 and 2). Miniature pigs, mongrel dogs, Macaca rhesus monkeys, and white rats have been used in the experiments. For fracture fixation, we have for soft-tissue used pins, plates, sutures, and screws; approximation, we have used sutures; for space obliteration, we have used these materials in a sponge form. The versatility of the material, because of its physical properties, allows its use in treating a number of conditions. The aforementioned experimental procedures have been successfully test,ed at the United States Army Institute of Dental Research. In conducting the research described in this report, the investigators adhered to the “Guide for Laboratory Animal Facilities and Care,” as promulgated by the Committee on the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Academy of Sciences-National Research Council. ‘Chief, Division of Oral-Pathology, United States Army Institute of Dental ‘Research, Walter Reed Army Medical Center, Washington, D. C. 20012. ““Brooke General Hospital, Brooke Army Medical Center, Fort Sam Houston, Texas.
28
Biodegradwble polylactic
Fig.
1. The methods
Fig.
2. Experimental
of PLA
usage
forms
of PLA
at the United
States
used in closing
hard
acid in frac~ture repair
Army
and
Institute
soft
29
of De1 It: tl Res lea1 dl.
tissues.
Because of the favorable results shown in the previous studies, th .e pr mt in order to evaluate the use of a PL A she in =I jeriment was undertaken orb lital fractures of the blowout type. ME WTHODS AND
MATERIALS
Twelve Macaca rhesus monkeys were used in the experiment. 1‘hey antesthetized with intramuscular Sernylan, 5 mg. per kilogram, an Id atrl
ere .ne,
0.02 mg., supplemented with sufficient intravenous pentobarbital sodium fog relaxation. The animals were prepared and draped in the usual manner, and a curvilinear incision was made in the region of the infraorbital rim. The infraorbital rim was reached by means of alternate sharp and blunt dissection. The periosteum was incised anal reflected superiorly, allowing the operator to visualize the floor of the orbit. With the use of a blunt instrument and a mallet, a fracture was made in the floor of the orbit without involving the infraorbital rim. After the fracture had been made, a sheet of polylactic acid approximately II.5 mm. thick was inserted into the orbital floor (Fig. 3). The sheet was adapted to the floor, and areas of excess were marked. The sheet was then removed, recontoured, and reinserted into the floor of the orbit, and the orbital contents were allowed to return to place. The wound was closed in layers with polylactic acid sutures of the same diameter as 4-O silk. Subcuticular sutures were used, thus eliminating the need for skin sutures (Fig. 4). The animals were killed, two at a time, at the following postoperative periods : 4, 8, 12, 18, 24, and 38 weeks. At the time of sacrifice, each animal was injected with Microfil,” as previously described, in order to study the vascular reaction around tho PLA plate.” The orbital area was dissected free, fixed, decalcified, and grossed into l-cm. thick blocks. These were then sectioned at 6 microns and stained with hematoxylin and co&n. CLINICAL
FINDINGS
The animals were observed daily for the first week, a,nd every 2 weeks thereafter. The first postoperative day showed minimal intraorbital edema and discoloration. This soon disappeared, and the position and movement of the eye were always normal. Healing and recovery were uneventful. The lo-day postoperative orbital area is shown in Fig. 5. “Canton
Biomedical
Products,
P. 0. Box
2017,
Boulder,
Colo.
%0303.
Volume Number
Biodegradable
33 1
Fig.
5. Wound
closure
polylactic
IO days
acid 4~ fractwe
repair
31
postoperatively.
Fig. 6. Four weeks postoperatively. Early differentiation of primitive cells into phagoeytic cells is seen against the PLA plate (top). The reaction is primarily osteoblastic. The blood vessels are partly fllled with Microfil. (Magnification, x140.) Fig. 7. Eight weeks postoperatively. Inflammation is decreasing. Giant cells are beginning to form against the PLA (left middle). (Magnification, x120.)
FINDINGS Four weeks
The 4-week samples demonstrated bone resorption resulting in a recontouring of the preoperative bone patterns. By this time, however, most of the reaction had become osteoblastic rather than osteoclastic (Fig. 6). At this time the inflammatory reaction was very mild and chronic in nature. Histologically, it showed only scattered plasma cells, lymphocytes, fibroblasts, and early deposition of collagen.
Big. 8. Eighteen weeks posi opcr:ltiT-ely. Note the lattice xrrxngenrcnt (uf~per ri,gRt,i x120.) Fig. 9. Twenty-four weeks postoper:rtively. seen. (Magnification, x120.)
Tlr~ rillous projections :1n11 one sm:dl gi:tnt The
villous
rell
extensions
are s~vn against the PLA. (ce?zt~r/. (Magnification, into
tile
PLA
The sinus side showed minimal osteoclastic activity as the bony being resorbed. New bone was being formed near the border of the and, in conjunction with the PLA, was forming a new orbital floor. clumping of phagocytic cells could be found. These cells resembled Eight
:UY~ easily
callus was PLA sheet, Occasional giant cells.
weeks
The 8-week tissue samples resembled the 4-meek ones. The bone was being remodeled across the floor of the orbit. This bony plate was in apposition to the fibrous connective-tissue capsule surrounding the PLA sheet. Inff ammation was chronic and minimal, with occasional elongated multinuclear phagocytic cells clinging to the PL,4 (Fig. 7). The edges of the PLA were slightly scalloped and roughened as a result. The fat cells surrounding the area had a normal appearance. Twelve
weeks
The lymphocytic and plasmacytic infiltration present earlier had disappeared. The fibrous capsule appeared to be little changed. A ring of phagocytic cells now surrounded the PLA. Sometimes this cell layer was more than one cell thick. The inner layer of cells had formed small projections which extended approximately 10 microns into the margin of the PLA sheet. Eighteen
weeks
These samples showed a decreased thickness of the connective-tissue capsule and an increase in the number and size of projections into the PbA sheet (Fig. 8). Many of these resembled a lattice with the framework formed by a
Volume Number
Biodegradable
33 1
Fig. IO. Thirty-eight weeks postoperatively. around the PLA, and some contain nuclei. The (Magnification, x120.)
double-layered membrane. ventional light microscopy. Twenty-four
polylactic
The double
Thus, each projection
acid in fracture
repair
33
clublike projections extend completely layer at this magnification is indistinct.
appeared
to be hollow
by con-
weeks
At 24 weeks there was little histologic change except in the villous extensions. These small projections had increased their length in many casesto 20 to 40 microns, with only a slight increase in diameter (Fig. 9). In certain areas the double-layered membrane was easily found. Thirty-eight
weeks
The main histologic change at 38 weeks was in the villous projections. By 38 weeks the double-layered projections had developed knobs at their ends, and many were now filled with a connective-tissue core. In some cases, nuclei had moved up into the projections, and nuclei from within the giant cells often appeared to have moved into the villi (Fig. 10). Occasionally, an extension of the inner channel of the cell ran beneath several villi and then disappeared into the surrounding connective tissue, as though it had formed a hollow channel. DISCUSSION
The movement of the eye by the monkey and the clinical observations indicate that the procedure was well tolerated. The actual phagoeytosis of the PLA began as early as 4 weeks and was still continuing at 38 weeks. This procedure appears to be slow and orderly and increases in speed only in the later time samples. Other studies with PLA have shown similar results, with a markedly increased rate of disappearance between
8 and 12 months. The final step appears to be abnost liquefaction oi the remaining PLA fragments. The disappearance of PLA from the tissues is not. accompanied by a severe inflammatory reac%ion. Bone was deposited immediately adjacent to the capsuh~, surrounding the PLA as it was resorbetl. This indicates a physiologic process by the body which does not inhibit new hone from forming and strengthening t,he site of fracture. Although this report covers 38 weeks, the PLA had not completely degraded. The gradual removal by the body was continuing. Because of the solvent effect exerted during the processing, it was impossible 60 measure the thickness of the remaining plate. However, over the 38-tveck period of this experiment, there \vas no clinical or histologic evidence which would contraindicate the use of PLA for this procedure. SUMMARY This study has demonstrated the following facts concerning the repair vf blowout fractures with a thin plate of polylactic acid (PLA) : 1. Resorption of PLA was accomplished by a peculiar phagocytic process involving phagocytic cells, giant cells, and villous projections. 2. PLA tissue compatibility was very good and no lymphocytic or plasmacytic infiltration was present after the eighth week. 3. Clinically, the function of the eye was normal. 4. PLA sheets of 1.5 mm. thickness were not completely resorbed during the 38-week course of the experiment. 5. This study substantiates our previous studies concerning the tolerance of t,issues for PLA. REFERENCES
1. Kulkami, R. K., Moore, E. G., Hegyeli, H. F., and Leonard, A. F.: Biodegradable Poly (Lactic Acid) Polymers, J. Biomed. Mater. Res. 5: 169, 1971. 2. Kulkarni, R. K., Pani, K. C., Neuman, C., and Leonard, F.: Polylactic Acid for Surgical Implants, Arch. Surg. 93: 539, 1966. 3. Cutright, D. E.. and Hunsuck. E. E.: Tissue Reaction to the Biodegradable Polylactic AcidSuture, OWL SURG. 31: lk,1971. 4. Cutright, D. E., Beasley, J. D., and Perez, B.: Histological Comparison of Polylactic and Polyglycolic Acid Suture, ORAL SURG. 32: 165, 1971. 5. Cutright, D. E., Hunsuck, E. E., and Beasley, J. D.: Fracture Reduction Using a Biodegradable Material, Polylactic Acid, J. Oral Surg. 29: 393-397, 1971. 6. Herrmann, J. B., Kelly, R. J., and Higgins, G. A.: Polyglycolic Acid Sutures, Arch. Surg. 100: 486-490, 1970. 7. Dardik, H., Dardik, I., Katz, A. R., Smith, R. B., Schwibner, B. H., and Laufman, H.: -4 New Absorbable Svnthetic Suture in Growing and Adult Primarv ” Vascular Anastomoses: Morphologic Study: Surgery 68: 1112-1121, lf70. 5. Anscombe, A. R., Hira, N., and Hunt, B.: The Use of a New Absorbable Suture Material (Polvnlvcolic Acid) in General Surgerv. Br. J. Sure. 57: 917-920. 9. Cutrigh”t, D. E., and Bhaskar, S. N.:” ’Oral Surgery-Oral Pathology Conference No. 21: A New Method of Demonstrating Microvasculature, ORAL SURG. 24: 422-426, 1967. Reprint requests to : Lt. Cal. D. E. Cutright Division of Oral Pathology U. S. Army Institute of Dental Research Walter Reetl Army Medical Center Washington, D. C. 20012
STATES
WALTER
REED
Lieutenant Lieutenant ARMY ARMY
INSTITUTE MEDICAL
Colonel, DC, USA,” and Colonel, DC, TJXA+* OF DENTAL
RESEARCH,
CENTER
In the repair of blowout fractures, resorption of polylactic acid (PLA) was accomplished by a peculiar phagocgtic process involving phagocytic cells, giant ceIIs, and villous projections. PT,A tissue compatibility was found to be very good. Clinically, the function of the eye was normal. This study substantiates previous studies concerning the tolerance of tissues for PLA.
S
ince 1965, there has been an increasing interest in the use of biodegradable materials for suturing, fracture fixation, etc. Those biodegradables which represent normal constituents of the metabolism of lactic acid have shown the most promise. The tissue reaction and disappearance rate of polylaetic acid (PLA) and polyglycolic acid (PGA) have been previously rep0rted.l.* These studies have shown very good tissue compatibility and demonstrated the feasibility of using these polymers in surgery. Both PLA and PGA have been made into sutures. Since 1968, here at the United States Army Institute of Dental Research, we have used PLA in various forms (Fig. 1.) and for different purposes (Figs. 1 and 2). Miniature pigs, mongrel dogs, Macaca rhesus monkeys, and white rats have been used in the experiments. For fracture fixation, we have for soft-tissue used pins, plates, sutures, and screws; approximation, we have used sutures; for space obliteration, we have used these materials in a sponge form. The versatility of the material, because of its physical properties, allows its use in treating a number of conditions. The aforementioned experimental procedures have been successfully test,ed at the United States Army Institute of Dental Research. In conducting the research described in this report, the investigators adhered to the “Guide for Laboratory Animal Facilities and Care,” as promulgated by the Committee on the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Academy of Sciences-National Research Council. ‘Chief, Division of Oral-Pathology, United States Army Institute of Dental ‘Research, Walter Reed Army Medical Center, Washington, D. C. 20012. ““Brooke General Hospital, Brooke Army Medical Center, Fort Sam Houston, Texas.
28
Biodegradwble polylactic
Fig.
1. The methods
Fig.
2. Experimental
of PLA
usage
forms
of PLA
at the United
States
used in closing
hard
acid in frac~ture repair
Army
and
Institute
soft
29
of De1 It: tl Res lea1 dl.
tissues.
Because of the favorable results shown in the previous studies, th .e pr mt in order to evaluate the use of a PL A she in =I jeriment was undertaken orb lital fractures of the blowout type. ME WTHODS AND
MATERIALS
Twelve Macaca rhesus monkeys were used in the experiment. 1‘hey antesthetized with intramuscular Sernylan, 5 mg. per kilogram, an Id atrl
ere .ne,
0.02 mg., supplemented with sufficient intravenous pentobarbital sodium fog relaxation. The animals were prepared and draped in the usual manner, and a curvilinear incision was made in the region of the infraorbital rim. The infraorbital rim was reached by means of alternate sharp and blunt dissection. The periosteum was incised anal reflected superiorly, allowing the operator to visualize the floor of the orbit. With the use of a blunt instrument and a mallet, a fracture was made in the floor of the orbit without involving the infraorbital rim. After the fracture had been made, a sheet of polylactic acid approximately II.5 mm. thick was inserted into the orbital floor (Fig. 3). The sheet was adapted to the floor, and areas of excess were marked. The sheet was then removed, recontoured, and reinserted into the floor of the orbit, and the orbital contents were allowed to return to place. The wound was closed in layers with polylactic acid sutures of the same diameter as 4-O silk. Subcuticular sutures were used, thus eliminating the need for skin sutures (Fig. 4). The animals were killed, two at a time, at the following postoperative periods : 4, 8, 12, 18, 24, and 38 weeks. At the time of sacrifice, each animal was injected with Microfil,” as previously described, in order to study the vascular reaction around tho PLA plate.” The orbital area was dissected free, fixed, decalcified, and grossed into l-cm. thick blocks. These were then sectioned at 6 microns and stained with hematoxylin and co&n. CLINICAL
FINDINGS
The animals were observed daily for the first week, a,nd every 2 weeks thereafter. The first postoperative day showed minimal intraorbital edema and discoloration. This soon disappeared, and the position and movement of the eye were always normal. Healing and recovery were uneventful. The lo-day postoperative orbital area is shown in Fig. 5. “Canton
Biomedical
Products,
P. 0. Box
2017,
Boulder,
Colo.
%0303.
Volume Number
Biodegradable
33 1
Fig.
5. Wound
closure
polylactic
IO days
acid 4~ fractwe
repair
31
postoperatively.
Fig. 6. Four weeks postoperatively. Early differentiation of primitive cells into phagoeytic cells is seen against the PLA plate (top). The reaction is primarily osteoblastic. The blood vessels are partly fllled with Microfil. (Magnification, x140.) Fig. 7. Eight weeks postoperatively. Inflammation is decreasing. Giant cells are beginning to form against the PLA (left middle). (Magnification, x120.)
FINDINGS Four weeks
The 4-week samples demonstrated bone resorption resulting in a recontouring of the preoperative bone patterns. By this time, however, most of the reaction had become osteoblastic rather than osteoclastic (Fig. 6). At this time the inflammatory reaction was very mild and chronic in nature. Histologically, it showed only scattered plasma cells, lymphocytes, fibroblasts, and early deposition of collagen.
Big. 8. Eighteen weeks posi opcr:ltiT-ely. Note the lattice xrrxngenrcnt (uf~per ri,gRt,i x120.) Fig. 9. Twenty-four weeks postoper:rtively. seen. (Magnification, x120.)
Tlr~ rillous projections :1n11 one sm:dl gi:tnt The
villous
rell
extensions
are s~vn against the PLA. (ce?zt~r/. (Magnification, into
tile
PLA
The sinus side showed minimal osteoclastic activity as the bony being resorbed. New bone was being formed near the border of the and, in conjunction with the PLA, was forming a new orbital floor. clumping of phagocytic cells could be found. These cells resembled Eight
:UY~ easily
callus was PLA sheet, Occasional giant cells.
weeks
The 8-week tissue samples resembled the 4-meek ones. The bone was being remodeled across the floor of the orbit. This bony plate was in apposition to the fibrous connective-tissue capsule surrounding the PLA sheet. Inff ammation was chronic and minimal, with occasional elongated multinuclear phagocytic cells clinging to the PL,4 (Fig. 7). The edges of the PLA were slightly scalloped and roughened as a result. The fat cells surrounding the area had a normal appearance. Twelve
weeks
The lymphocytic and plasmacytic infiltration present earlier had disappeared. The fibrous capsule appeared to be little changed. A ring of phagocytic cells now surrounded the PLA. Sometimes this cell layer was more than one cell thick. The inner layer of cells had formed small projections which extended approximately 10 microns into the margin of the PLA sheet. Eighteen
weeks
These samples showed a decreased thickness of the connective-tissue capsule and an increase in the number and size of projections into the PbA sheet (Fig. 8). Many of these resembled a lattice with the framework formed by a
Volume Number
Biodegradable
33 1
Fig. IO. Thirty-eight weeks postoperatively. around the PLA, and some contain nuclei. The (Magnification, x120.)
double-layered membrane. ventional light microscopy. Twenty-four
polylactic
The double
Thus, each projection
acid in fracture
repair
33
clublike projections extend completely layer at this magnification is indistinct.
appeared
to be hollow
by con-
weeks
At 24 weeks there was little histologic change except in the villous extensions. These small projections had increased their length in many casesto 20 to 40 microns, with only a slight increase in diameter (Fig. 9). In certain areas the double-layered membrane was easily found. Thirty-eight
weeks
The main histologic change at 38 weeks was in the villous projections. By 38 weeks the double-layered projections had developed knobs at their ends, and many were now filled with a connective-tissue core. In some cases, nuclei had moved up into the projections, and nuclei from within the giant cells often appeared to have moved into the villi (Fig. 10). Occasionally, an extension of the inner channel of the cell ran beneath several villi and then disappeared into the surrounding connective tissue, as though it had formed a hollow channel. DISCUSSION
The movement of the eye by the monkey and the clinical observations indicate that the procedure was well tolerated. The actual phagoeytosis of the PLA began as early as 4 weeks and was still continuing at 38 weeks. This procedure appears to be slow and orderly and increases in speed only in the later time samples. Other studies with PLA have shown similar results, with a markedly increased rate of disappearance between
8 and 12 months. The final step appears to be abnost liquefaction oi the remaining PLA fragments. The disappearance of PLA from the tissues is not. accompanied by a severe inflammatory reac%ion. Bone was deposited immediately adjacent to the capsuh~, surrounding the PLA as it was resorbetl. This indicates a physiologic process by the body which does not inhibit new hone from forming and strengthening t,he site of fracture. Although this report covers 38 weeks, the PLA had not completely degraded. The gradual removal by the body was continuing. Because of the solvent effect exerted during the processing, it was impossible 60 measure the thickness of the remaining plate. However, over the 38-tveck period of this experiment, there \vas no clinical or histologic evidence which would contraindicate the use of PLA for this procedure. SUMMARY This study has demonstrated the following facts concerning the repair vf blowout fractures with a thin plate of polylactic acid (PLA) : 1. Resorption of PLA was accomplished by a peculiar phagocytic process involving phagocytic cells, giant cells, and villous projections. 2. PLA tissue compatibility was very good and no lymphocytic or plasmacytic infiltration was present after the eighth week. 3. Clinically, the function of the eye was normal. 4. PLA sheets of 1.5 mm. thickness were not completely resorbed during the 38-week course of the experiment. 5. This study substantiates our previous studies concerning the tolerance of t,issues for PLA. REFERENCES
1. Kulkami, R. K., Moore, E. G., Hegyeli, H. F., and Leonard, A. F.: Biodegradable Poly (Lactic Acid) Polymers, J. Biomed. Mater. Res. 5: 169, 1971. 2. Kulkarni, R. K., Pani, K. C., Neuman, C., and Leonard, F.: Polylactic Acid for Surgical Implants, Arch. Surg. 93: 539, 1966. 3. Cutright, D. E.. and Hunsuck. E. E.: Tissue Reaction to the Biodegradable Polylactic AcidSuture, OWL SURG. 31: lk,1971. 4. Cutright, D. E., Beasley, J. D., and Perez, B.: Histological Comparison of Polylactic and Polyglycolic Acid Suture, ORAL SURG. 32: 165, 1971. 5. Cutright, D. E., Hunsuck, E. E., and Beasley, J. D.: Fracture Reduction Using a Biodegradable Material, Polylactic Acid, J. Oral Surg. 29: 393-397, 1971. 6. Herrmann, J. B., Kelly, R. J., and Higgins, G. A.: Polyglycolic Acid Sutures, Arch. Surg. 100: 486-490, 1970. 7. Dardik, H., Dardik, I., Katz, A. R., Smith, R. B., Schwibner, B. H., and Laufman, H.: -4 New Absorbable Svnthetic Suture in Growing and Adult Primarv ” Vascular Anastomoses: Morphologic Study: Surgery 68: 1112-1121, lf70. 5. Anscombe, A. R., Hira, N., and Hunt, B.: The Use of a New Absorbable Suture Material (Polvnlvcolic Acid) in General Surgerv. Br. J. Sure. 57: 917-920. 9. Cutrigh”t, D. E., and Bhaskar, S. N.:” ’Oral Surgery-Oral Pathology Conference No. 21: A New Method of Demonstrating Microvasculature, ORAL SURG. 24: 422-426, 1967. Reprint requests to : Lt. Cal. D. E. Cutright Division of Oral Pathology U. S. Army Institute of Dental Research Walter Reetl Army Medical Center Washington, D. C. 20012