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Degradation kinetics of biodegradable dl -polylactic acid biodegradable implants depending on the site of implantation
Copyright © Munksgaard 1994
Int..~ Oral Maxillofac. Surg. 1994; 23:443 445 Printed in Denmark. All rights reserved
InternationalJournal of
Oral&
MaxillofacialSurgery ISSN 0901-5027
Degradation kinetics of biodegradable DL-polylactic acid biodegradable implants depending on the site of
implantation
A. Tschakaloff 1, H.W. Losken 2, R. von Oepen 3, W. MichaelP, O. Moritz 3, M. P. Mooney 4, A. Losken 4 1Klinik for Kiefer- und Gesichtschirurgie, Medizinische Universitft zu L0beck, L0beck, Germany; 2Department of Plastic, Reconstructive, and Maxillofacial Surgery, University of Pittsburgh, Pittsburgh, PA, USA; 31nstitut for Kunststoffverarbeitung, Rheinisch-Westf~ilische Technische Universitft Aachen, Aachen, Germany; 4Department of Physical Anthropology and Anatomy, University of Pittsburgh, Pittsburgh, PA, USA
A. Tschakaloff H. W. Losken, R. yon Oepen, W. Michaeli, O. Moritz, M. P. Mooney, A. Losken: Degradation kinetics of biodegradable DL-polylactic acid biodegradable implants depending on the site of implantation. Int. J. Oral Maxillofac. Surg. 1994; 23." 443 445. © Munksgaard, 1994 Abstract. A recently developed biodegradable system made of DL-polylactic acid (DL-PLA) for internal fixation of non-weight-bearing bones of the craniofacial skeleton was investigated. The plates were used for rigid fixation of experimental nasal bone fractures in 20 New Zealand white rabbits. In addition, prebent plates were placed in subcutaneous pockets in the backs of the animals. The material was removed after 7, 14, 28, and 42 days, and bending angles, plate stability, molecular weights (MW), and histologic analyses were studied. A significant decrease of MW over time and a difference in MW loss, showing a faster degradation subcutaneously, were observed. Plate stability did not decrease during the interval of 6 weeks, but a loss of bending angle was found in all prebent implants. This effect was caused by memory of DL-PLA. The results suggest that memory of biodegradable materials should be investigated before clinical application and that degradation rates differ according to the site of implantation.
The use of plates and screws for rigid fixation of facial bones has aroused concern about the negative long-term effects of metallic implants ~,8. Animal studies have shown that plates may interfere with growth 4. Allergies and artifact formation on computed tomography (CT) or magnetic resonance imaging (MRI) scans may be another disadvantage9, and drifting of the plates and screws through the cranium after craniofacial surgery in early childhood has been reported 6. Rigid fixation systems made of biodegradable polymers may solve these problems. They have no negative effects
on CT 11 or MRI scans, and negative effects on growing bones are not to be expected 3. Materials with the potential for use as plates and screws are polyglycolic acid (PGA), L-polylactic acid (L-PLA), and DL-polylactic acid (DI,PLA) or their copolymers. They are available in various molecular weights and as copolymers that differ in stability and degradation rates 2. The goal of the present study was to create an animal model for fractures of non-weight-bearing facial bones, and to study the stability and degradation behavior of plates and screws made of DLPLA (Resomer R 207, Boehringer In-
Key words: DL-polylactic acid; biodegradable plate and screw system; molecular weight; rabbits. Accepted for publication 1 January 1994
gelheim, Ingelheim, Germany) over a period of 6 weeks.
Material and methods Plates and screws for this study were injection molded7, and packed and stored under sterile conditions. A custom-made devicewas used for standardized bending of the plates at angles of 30°, 45°, and 60° by heat. Twenty, 6-week-old New Zealand white rabbits were used in the study. The animals were anesthetized with an intramuscular injection of a solution of ketamine hydrochloride and xylazine. The nasal bones were mobilized at the frontonasal and nasomaxillary suture. Bilateral fractures were created 10 mm distally of
444
T s c h a k a l o f f et aL
ence in bone healing between the groups, Biodegradable plates and screws did not seem to elicit any allergic reaction.
Discussion
.
.
.
.
.
~,:
f
,
Fig. 1. Nasal bones after exposure and mobilization at frontonasal and nasomaxillary suture. Bilateral fractures were created 10 mm distally of nasion with surgical clamps. In experimental group, fractures were reduced and fixed with biodegradable plates and screws made of OLPLA.
the nasion, in the control group (n=8), the fractures were reduced and the periosteum was closed. The experimental group (n= 12) underwent rigid fixation with biodegradable plates and screws (Fig. 1). In addition, plates prebent at angles of 30°, 45°, and 60° were implanted in subcutaneous pockets. The animals were killed at 1, 2, 4, and 6 weeks after surgery. Plate shape, stability, and mol. wt. were measmed and histologic analyses of the nasal fracture sites were obtained. Stability was measured by 3-point bending at a temperature of 37°C and a speed of 25 ram/rain. The mol. wt. was measured at surgery and 7, 14, 28, and 42 days postoperatively, after the plates were dissolved in chloroform and the solution was run through an Ubbelohde viscosimeter. The explanted bones were fixed in formalin and embedded in paraffin. A standard hematoxylin-and-eosin histologic analysis was obtained.
urements revealed a significant loss over time (Fig. 3). The highest rate of degradation was observed subcutaneously, followed by subperiosteal and in vitro conditions. Histologically, there was no differ-
In the present study, a new animal model in rabbits was created for the investigation of fractures of non-weightbearing facial boneS. This model allowed in vivo testing o f a biodegradable system for rigid fixation of facial bones. Stability, tissue tolerance, and degradation rates were found to be acceptable for possible clinical use o f this material in the future. However, the failure of DL-PLA plates to maintain their bending angle under in vivo conditions was discovered. Because the temperature of glass transition for R 207 is 58°C, it is surprising that the plates showed plastic m e m o r y at body-temperature ranges. A possible explanation may be that water uptake leads to a decrease of glass transition temperature, causing plastic m e m o r y in vivo. The other important finding of the study is the different rate of degradation between the subcutaneous and the subperiosteal site of implantation. Both degradation rates differed significantly from in vitro rates, suggesting that DL-
max. t e n s i o n N / m m 2 120
100
80 6040-
Results The rabbits tolerated the surgical procedures well, and all operative sites healed uneventfully. At the time of removal after 1 week of implantation, all plates in the subcutaneous pockets in the backs had lost their bend and had straightened to angles ranging around 10 °. The loss of bend was found in all animals at any interval. N o significant loss of plate stability over the period of observation at both implantation sites was noted (Fig. 2), and mol. wt. meas-
20-
0
5
10
15
20
25
30
35
40
45
50
days postoperatively subcutaneous 4- control, nose -~ subperiosteal Fig. 2. Stability of nasal bones was measured with 3-point bending at temperature of 37°C and speed of 25 mm/min. No significant loss of plate stability over period of observation at both implantation sites was noted.
Degradation o f D L - P L A implants
Molecular Weight x 1000 140 120" 100 806040200 0
I
I
I
I
I
I
I
I
I
I
5
10
15
20
25
30
35
40
45
50
days -'-
postoperatively
in vitro -I- subcutaneous
--x- subperiosteal
Fig. 3. Loss of mol. wt. over time. Note difference between in vitro findings and within different sites of implantation.
P L A is a b s o r b e d faster in vivo t h a n in vitro. Because hydrolysis has been f o u n d to be the only pathway of degradation 1°, differences in perfusion m a y explain this effect. These differences in mol. wt. loss h a d n o effect on plate stability d u r i n g the interval o f observation for the material utilized in this study (R 207). However, it supports the a r g u m e n t t h a t testing of biodegradable systems for rigid fixation should be done under conditions that m a y simulate future clinical use. In summary, the lack of shape-stability o f DL-PLA plates poses a severe risk if they are used in patients. A disp l a c e m e n t of b o n y fragments m a y occur a n d lead to u n f a v o r a b l e functional a n d cosmetic results. Therefore, we reco m m e n d the screening o f future biodeg r a d a b l e systems for plastic memory.
References 1. Bos RM, ROZEMAFR, BOERING G, P~NNINGS AJ. Biodegradable osteosynthesis in maxillofacial surgery. Clin Oral Maxillofac Surg North Am 1990: 2(4): 745-50. 2. EITENM/JLLER J, GERLACH KL, SCHMICKAL T, M U H R G . Semirigide P l a t tenosteosynthesen unter Verwendung absorbierbarer Polymere als temporfire Implantate. Chirurg 1987: 58: 831-9. 3. EPLEY BL, SAOOVE AM. Effects of resorbable fixation on craniofacial skeletal growth: a pilot experimental study. J Craniofac Surg 1992: 3: 190-6. 4; LIN KY, BARTLETT SP, YAREMCHUK M J, GROSSMANN RF, U D U P A J K , W H I T A K E R LA. An experimental study on the effect of rigid fixation on the developing craniofacial skeleton. Plast Reconstr Surg 1991: 87: 229-35.
445
5. LOSKEN HW, TSCHAKALOFF A, MOONEY MP, et al. The effects of frontal bone advancement with or without biodegradable microplates on advancement stability and compensatory craniofacial growth changes in rabbits with experimental coronal suture immobilization. Craniofacial Surgery - Proceedings of the Fourth Meeting of International Society of Craniomaxillofacial Surgery. MONTOYA, AD, ed. Bologna: Monduzzi Editore, 1992: 219-23. 6. MUNRO I. Management of craniofacial anomalies: rationale of timing and growth implications. Pre-Conference Program of the 50th Anniversary Meeting of the American Cleft Palate-Craniofacial Association, Pittsburgh, 20 April 1993, Pittsburgh, PA, USA. 7. VON OEPEN R, MICHAELI W. Injection molding of biodegradable implants. Clin Mater 1992: 10: 21-8. 8. POLLEY JW, HUNG K-F, COHEN M, FIGUEROAAA. The effects of rigid microfixation on craniofacial development. Paper presented at International Symposium on Craniofacial Surgery, 21-24 October 1992, Chicago, IL, USA. 9. SULLWANPK, SMITHJ. Craniofacial metallic implants: their effect on MRI safety and MR and CT image quality. Paper presented at International Symposium on Craniofacial Surgery, 21 24 October 1992, Chicago, IL USA. 10. Toxicology of polymers of L- and D-lactide and glycolide and assessment of their incorporation into man. Ingelheim: Boehringer Ingelheim KG, December 1987. 11. TSCHAKALOEFA, LOSKENHW, LALIKOSJ, et al. Experimental studies on the effects of DL-polylactic acid biodegradable plates and screws in rabbits: computerized tomography and molecular weight toss. J Craniofac Surg 1993: 4: 223-7.
Address: A. Tschakaloff Klinik fiir Kiefer- und Gesichtschirurgie Medizinische Universitdt zu LCibeck Ratzeburger Allee 160 D-23538 Lffbeck Germany
Int..~ Oral Maxillofac. Surg. 1994; 23:443 445 Printed in Denmark. All rights reserved
InternationalJournal of
Oral&
MaxillofacialSurgery ISSN 0901-5027
Degradation kinetics of biodegradable DL-polylactic acid biodegradable implants depending on the site of
implantation
A. Tschakaloff 1, H.W. Losken 2, R. von Oepen 3, W. MichaelP, O. Moritz 3, M. P. Mooney 4, A. Losken 4 1Klinik for Kiefer- und Gesichtschirurgie, Medizinische Universitft zu L0beck, L0beck, Germany; 2Department of Plastic, Reconstructive, and Maxillofacial Surgery, University of Pittsburgh, Pittsburgh, PA, USA; 31nstitut for Kunststoffverarbeitung, Rheinisch-Westf~ilische Technische Universitft Aachen, Aachen, Germany; 4Department of Physical Anthropology and Anatomy, University of Pittsburgh, Pittsburgh, PA, USA
A. Tschakaloff H. W. Losken, R. yon Oepen, W. Michaeli, O. Moritz, M. P. Mooney, A. Losken: Degradation kinetics of biodegradable DL-polylactic acid biodegradable implants depending on the site of implantation. Int. J. Oral Maxillofac. Surg. 1994; 23." 443 445. © Munksgaard, 1994 Abstract. A recently developed biodegradable system made of DL-polylactic acid (DL-PLA) for internal fixation of non-weight-bearing bones of the craniofacial skeleton was investigated. The plates were used for rigid fixation of experimental nasal bone fractures in 20 New Zealand white rabbits. In addition, prebent plates were placed in subcutaneous pockets in the backs of the animals. The material was removed after 7, 14, 28, and 42 days, and bending angles, plate stability, molecular weights (MW), and histologic analyses were studied. A significant decrease of MW over time and a difference in MW loss, showing a faster degradation subcutaneously, were observed. Plate stability did not decrease during the interval of 6 weeks, but a loss of bending angle was found in all prebent implants. This effect was caused by memory of DL-PLA. The results suggest that memory of biodegradable materials should be investigated before clinical application and that degradation rates differ according to the site of implantation.
The use of plates and screws for rigid fixation of facial bones has aroused concern about the negative long-term effects of metallic implants ~,8. Animal studies have shown that plates may interfere with growth 4. Allergies and artifact formation on computed tomography (CT) or magnetic resonance imaging (MRI) scans may be another disadvantage9, and drifting of the plates and screws through the cranium after craniofacial surgery in early childhood has been reported 6. Rigid fixation systems made of biodegradable polymers may solve these problems. They have no negative effects
on CT 11 or MRI scans, and negative effects on growing bones are not to be expected 3. Materials with the potential for use as plates and screws are polyglycolic acid (PGA), L-polylactic acid (L-PLA), and DL-polylactic acid (DI,PLA) or their copolymers. They are available in various molecular weights and as copolymers that differ in stability and degradation rates 2. The goal of the present study was to create an animal model for fractures of non-weight-bearing facial bones, and to study the stability and degradation behavior of plates and screws made of DLPLA (Resomer R 207, Boehringer In-
Key words: DL-polylactic acid; biodegradable plate and screw system; molecular weight; rabbits. Accepted for publication 1 January 1994
gelheim, Ingelheim, Germany) over a period of 6 weeks.
Material and methods Plates and screws for this study were injection molded7, and packed and stored under sterile conditions. A custom-made devicewas used for standardized bending of the plates at angles of 30°, 45°, and 60° by heat. Twenty, 6-week-old New Zealand white rabbits were used in the study. The animals were anesthetized with an intramuscular injection of a solution of ketamine hydrochloride and xylazine. The nasal bones were mobilized at the frontonasal and nasomaxillary suture. Bilateral fractures were created 10 mm distally of
444
T s c h a k a l o f f et aL
ence in bone healing between the groups, Biodegradable plates and screws did not seem to elicit any allergic reaction.
Discussion
.
.
.
.
.
~,:
f
,
Fig. 1. Nasal bones after exposure and mobilization at frontonasal and nasomaxillary suture. Bilateral fractures were created 10 mm distally of nasion with surgical clamps. In experimental group, fractures were reduced and fixed with biodegradable plates and screws made of OLPLA.
the nasion, in the control group (n=8), the fractures were reduced and the periosteum was closed. The experimental group (n= 12) underwent rigid fixation with biodegradable plates and screws (Fig. 1). In addition, plates prebent at angles of 30°, 45°, and 60° were implanted in subcutaneous pockets. The animals were killed at 1, 2, 4, and 6 weeks after surgery. Plate shape, stability, and mol. wt. were measmed and histologic analyses of the nasal fracture sites were obtained. Stability was measured by 3-point bending at a temperature of 37°C and a speed of 25 ram/rain. The mol. wt. was measured at surgery and 7, 14, 28, and 42 days postoperatively, after the plates were dissolved in chloroform and the solution was run through an Ubbelohde viscosimeter. The explanted bones were fixed in formalin and embedded in paraffin. A standard hematoxylin-and-eosin histologic analysis was obtained.
urements revealed a significant loss over time (Fig. 3). The highest rate of degradation was observed subcutaneously, followed by subperiosteal and in vitro conditions. Histologically, there was no differ-
In the present study, a new animal model in rabbits was created for the investigation of fractures of non-weightbearing facial boneS. This model allowed in vivo testing o f a biodegradable system for rigid fixation of facial bones. Stability, tissue tolerance, and degradation rates were found to be acceptable for possible clinical use o f this material in the future. However, the failure of DL-PLA plates to maintain their bending angle under in vivo conditions was discovered. Because the temperature of glass transition for R 207 is 58°C, it is surprising that the plates showed plastic m e m o r y at body-temperature ranges. A possible explanation may be that water uptake leads to a decrease of glass transition temperature, causing plastic m e m o r y in vivo. The other important finding of the study is the different rate of degradation between the subcutaneous and the subperiosteal site of implantation. Both degradation rates differed significantly from in vitro rates, suggesting that DL-
max. t e n s i o n N / m m 2 120
100
80 6040-
Results The rabbits tolerated the surgical procedures well, and all operative sites healed uneventfully. At the time of removal after 1 week of implantation, all plates in the subcutaneous pockets in the backs had lost their bend and had straightened to angles ranging around 10 °. The loss of bend was found in all animals at any interval. N o significant loss of plate stability over the period of observation at both implantation sites was noted (Fig. 2), and mol. wt. meas-
20-
0
5
10
15
20
25
30
35
40
45
50
days postoperatively subcutaneous 4- control, nose -~ subperiosteal Fig. 2. Stability of nasal bones was measured with 3-point bending at temperature of 37°C and speed of 25 mm/min. No significant loss of plate stability over period of observation at both implantation sites was noted.
Degradation o f D L - P L A implants
Molecular Weight x 1000 140 120" 100 806040200 0
I
I
I
I
I
I
I
I
I
I
5
10
15
20
25
30
35
40
45
50
days -'-
postoperatively
in vitro -I- subcutaneous
--x- subperiosteal
Fig. 3. Loss of mol. wt. over time. Note difference between in vitro findings and within different sites of implantation.
P L A is a b s o r b e d faster in vivo t h a n in vitro. Because hydrolysis has been f o u n d to be the only pathway of degradation 1°, differences in perfusion m a y explain this effect. These differences in mol. wt. loss h a d n o effect on plate stability d u r i n g the interval o f observation for the material utilized in this study (R 207). However, it supports the a r g u m e n t t h a t testing of biodegradable systems for rigid fixation should be done under conditions that m a y simulate future clinical use. In summary, the lack of shape-stability o f DL-PLA plates poses a severe risk if they are used in patients. A disp l a c e m e n t of b o n y fragments m a y occur a n d lead to u n f a v o r a b l e functional a n d cosmetic results. Therefore, we reco m m e n d the screening o f future biodeg r a d a b l e systems for plastic memory.
References 1. Bos RM, ROZEMAFR, BOERING G, P~NNINGS AJ. Biodegradable osteosynthesis in maxillofacial surgery. Clin Oral Maxillofac Surg North Am 1990: 2(4): 745-50. 2. EITENM/JLLER J, GERLACH KL, SCHMICKAL T, M U H R G . Semirigide P l a t tenosteosynthesen unter Verwendung absorbierbarer Polymere als temporfire Implantate. Chirurg 1987: 58: 831-9. 3. EPLEY BL, SAOOVE AM. Effects of resorbable fixation on craniofacial skeletal growth: a pilot experimental study. J Craniofac Surg 1992: 3: 190-6. 4; LIN KY, BARTLETT SP, YAREMCHUK M J, GROSSMANN RF, U D U P A J K , W H I T A K E R LA. An experimental study on the effect of rigid fixation on the developing craniofacial skeleton. Plast Reconstr Surg 1991: 87: 229-35.
445
5. LOSKEN HW, TSCHAKALOFF A, MOONEY MP, et al. The effects of frontal bone advancement with or without biodegradable microplates on advancement stability and compensatory craniofacial growth changes in rabbits with experimental coronal suture immobilization. Craniofacial Surgery - Proceedings of the Fourth Meeting of International Society of Craniomaxillofacial Surgery. MONTOYA, AD, ed. Bologna: Monduzzi Editore, 1992: 219-23. 6. MUNRO I. Management of craniofacial anomalies: rationale of timing and growth implications. Pre-Conference Program of the 50th Anniversary Meeting of the American Cleft Palate-Craniofacial Association, Pittsburgh, 20 April 1993, Pittsburgh, PA, USA. 7. VON OEPEN R, MICHAELI W. Injection molding of biodegradable implants. Clin Mater 1992: 10: 21-8. 8. POLLEY JW, HUNG K-F, COHEN M, FIGUEROAAA. The effects of rigid microfixation on craniofacial development. Paper presented at International Symposium on Craniofacial Surgery, 21-24 October 1992, Chicago, IL, USA. 9. SULLWANPK, SMITHJ. Craniofacial metallic implants: their effect on MRI safety and MR and CT image quality. Paper presented at International Symposium on Craniofacial Surgery, 21 24 October 1992, Chicago, IL USA. 10. Toxicology of polymers of L- and D-lactide and glycolide and assessment of their incorporation into man. Ingelheim: Boehringer Ingelheim KG, December 1987. 11. TSCHAKALOEFA, LOSKENHW, LALIKOSJ, et al. Experimental studies on the effects of DL-polylactic acid biodegradable plates and screws in rabbits: computerized tomography and molecular weight toss. J Craniofac Surg 1993: 4: 223-7.
Address: A. Tschakaloff Klinik fiir Kiefer- und Gesichtschirurgie Medizinische Universitdt zu LCibeck Ratzeburger Allee 160 D-23538 Lffbeck Germany