use of triethylcitrate plasticizer in the production pf pla implants with different degradation t

7
JOURNAL OF MATERIALS SCIENCE: MATERIALS IN MEDICINE 14 (2003) 635±640 Use of triethylcitrate plasticizer in the production of poly-L-lactic acid implants with different degradation times S. M. N. SCAPIN, D. R. M. SILVA, P. P. JOAZEIRO, M. C. ALBERTO-RINCON* Department of Histology and Embryology, Institute of Biology, State University of Campinas (UNICAMP), PO Box 6109, 13083-970, Campinas, SP, Brazil E-mail: [email protected] R. M. LUCIANO, E. A. R. DUEK Department of Material Engineering, Faculty of Mechanical Engineering, State University of Campinas (UNICAMP), PO Box 6109, 13083-970, Campinas, SP, Brazil Bioabsorbable materials have been widely used in the repair of damaged tissue as well as in the controlled release of drugs and as a supports for cultured cells. The degradation time of poly-L-(lactic acid) (PLLA) may be controlled by altering the polymer porosity through the addition of the plasticizer triethylcitrate. This in turn in¯uences the extent cellular in®ltration. In this study, we examined the degradation of PLLA membranes containing different concentrations of plasticizer. PLLA discs were implanted subcutaneouly in rats and withdrawn 2, 14 and 60 days after implantation. The samples were processed for light microscopy and scanning electron microscopy (SEM). Polymer degradation was proportional to the concentration of plasticizer, indicating that triethylcitrate could affect the degradation time of the implants, without damaging the polymer biocompatibility. # 2003 Kluwer Academic Publishers Introduction The increasing use of arti®cial materials to repair human tissues has led to development of new products to meet this demand. The availability of polymers that can be absorbed by the host organism has eliminated the need for a second surgery to remove the implanted material, and this in turn has reduced hospital expenses, surgical complications and the time needed for recuperation [1]. Poly-L-(lactic acid) (PLLA) is a semi-crystalline polyester that can be degraded through hydrolysis of its ester bonds, and has considerable strength retention capacity and excellent biocompatibility. Non-toxic degradation products are excreted by the kidneys or eliminated as carbon dioxide and water through the tricarboxylic acid cycle [2]. Although bioabsorbable materials are recognized by the organism as ``foreign bodies'' before their absorption, their ®nite exposure time and the mild in¯ammatory response they elicit are clearly advantageous. Biomaterials have a variety of applications, including the construction of orthopedic protheses and guided tissue regeneration [3], controlled release of drugs [4, 5], as a type support for cultured cells [6] and tissue engineering [7, 8]. The extent of polymer degradation in¯uences not only the type and intensity of the in¯ammatory response [9], but also its functional application, faster or slower degradation depending on the tissue to be repaired. Many factors may in¯uence the kinetics of biomaterials degradation, including the molecules chemical structure, mass, super®cial texture, porosity, pore dimensions, size and shape of the implant, site of implantation, and the microlocomotion of polymer fragments at the interface with adjacent tissue [10]. The inclusion of a plasticizer in polymer chains decreases the interaction among them but increases the ¯exibility, porosity and degradation of the polymer [11, 12]. In this work, we examined the biological properties and degradation process of PLLA membranes containing different concentrations (5, 9 and 11%) of the plasticizer triethylcitrate and assessed their interaction with adjacent tissue in vivo. Materials and methods Production of implants PLLA (MW 300 000) was provided as pellets (Medsorb Technologies International L.P., Cincinnati, OH, USA). Ten grams of polymer were dissolved in 100 mL of methylene chloride (CH 2 Cl 2 , Merck KgaA, Darmstadt, Germany) containing 5%, 9% or 11% triethylcitrate (Aldrich, Milwaukee, WI, USA) in a closed recipient at room temperature. The mixture was then poured on to a glass plate (100 cm 2 ), which was air-dried (air ¯ow of 1 L/min) at room temperature. After 15 h, the membranes were removed from the plates and vacuum dried for 24 h. *Author to whom all correspondence should be addressed. 0957±4530 # 2003 Kluwer Academic Publishers 635

Upload: toufik

Post on 08-Dec-2015

213 views

Category:

Documents


0 download

DESCRIPTION

TRIACETYL

TRANSCRIPT

������� �� ������ ������� ������ �� ������� �� � ���� � �������

��� �� ���������� �� �� �������� �� �� ������������ ������� ���� ��� ���� ��� ��� ������������� � ���� �����

�� �� �� ������ � �� �� ��� � �� �� �������� �� �� ������������������������� �� ���� ��� ��������� �� ������ ������ ����� ������ ��� ������� ������� !� " �# $%&'� %(&)(*'+&� ������� � � � ���,���*����- ����.�/���.���0��

�� �� ������� �� �� �� ������������� �������� ������������ 1�.���� ��.2���.�� ������������ ����� ������ ��� ������� ������� !� " �# $%&'� %(&)(*'+&� ������� � � � ���,��

������������� �!������ "�#� ���$ %�&��' (��& �$ !"� ��)��� �* &� �+�& !���(� �� %��� �� �$!"� ,�$!�����& ������� �* &�(+� �$& �� � �())��!� *�� ,(�!(��& ,����� �"� &�+��&�!��$ !� � �*)��'���-��,!�, �,�&. -����. �' �� ,�$!�����& �' ��!���$+ !"� )��' �� )�����!' !"��(+" !"��&&�!��$ �* !"� )���!�,�/�� !���!"'�,�!��!�� �"�� �$ !(�$ �$0(�$,�� !"� �1!�$! ,���(��� �$2�!��!��$��$ !"�� �!(&' %� �1� �$�& !"� &�+��&�!��$ �* ���� � ���$�� ,�$!��$�$+ &�**���$!,�$,�$!��!��$� �* )���!�,�/��� ���� &��,� %��� � )��$!�& �(�,(!�$��(�' �$ ��!� �$&%�!"&��%$ 3 45 �$& 67 &�'� �*!�� � )��$!�!��$� �"� �� )��� %��� )��,����& *�� ��+"! �,���,�)' �$& �,�$$�$+ ���,!��$ �,���,�)' -���.� ���' �� &�+��&�!��$ %��)��)��!��$�� !� !"� ,�$,�$!��!��$ �* )���!�,�/�� �$&�,�!�$+ !"�! !���!"'�,�!��!� ,�(�& �**�,! !"�&�+��&�!��$ !� � �* !"� � )��$!� %�!"�(! &� �+�$+ !"� )��' �� ���,� )�!�����!'�� 3&&( 4��5�� �.�����. ���� 2��

�������������� ����� !��" #!� $% �&�'�� ( ) &��� (! &$ ��* �� �#) �

&�!!#�! � ! (�+ &$ +�,�($*)��& $% ��- *�$+#�&! &$ )��&

&��! +�) �+. �� , �( /�(�&0 $% *$(0)��! &� & � � /�

/!$�/�+ /0 &�� �$!& $�" ��!) � ! �(�)�� &�+ &�� ���+

%$� !��$�+ !#�"��0 &$ ��)$,� &�� �)*( �&�+ ) &��� (1

�+ &��! �� &#�� � ! ��+#��+ �$!*�& ( �2*��!�!1 !#�"�� (

�$)*(�� &�$�! �+ &�� &�)� ���+�+ %$� ���#*�� &�$� 345.

6$(07�7�( �&�� ��+� �6���� �! !�)�7��0!& ((���

*$(0�!&�� &� & � � /� +�"� +�+ &��$#"� �0+�$(0!�! $% �&!

�!&�� /$�+!1 �+ � ! �$�!�+�� /(� !&���"&� ��&��&�$�

� * ��&0 �+ �2��((��& /�$�$)* &�/�(�&0. �$�7&$2��

+�"� + &�$� *�$+#�&! �� �2���&�+ /0 &�� 8�+��0! $�

�(�)�� &�+ ! � �/$� +�$2�+� �+ - &�� &��$#"� &��

&��� �/$20(�� ��+ �0�(� 3�5. �(&�$#"� /�$ /!$�/ /(�

) &��� (! �� ���$"��9�+ /0 &�� $�" ��!) ! ::%$���"�

/$+��!;; /�%$�� &���� /!$�*&�$�1 &���� '��&� �2*$!#��

&�)� �+ &�� )�(+ ��< )) &$�0 ��!*$�!� &��0 �(���& ��

�(� �(0 +, �& "�$#!.

=�$) &��� (! � ,� , ���&0 $% **(�� &�$�!1 ���(#+��"

&�� �$�!&�#�&�$� $% $�&�$*�+�� *�$&��!�! �+ "#�+�+

&�!!#� ��"���� &�$� 3�51 �$�&�$((�+ ��(� !� $% +�#"! 3�1 �51

! &0*� !#**$�& %$� �#(&#��+ ��((! 3�5 �+ &�!!#�

��"�������" 3>1 ?5. �� �2&��& $% *$(0)�� +�"� + &�$�

��<#����! �$& $�(0 &�� &0*� �+ ��&��!�&0 $% &��

��< )) &$�0 ��!*$�!� 3@51 /#& (!$ �&! %#��&�$� (

**(�� &�$�1 % !&�� $� !($-�� +�"� + &�$� +�*��+��" $�

&�� &�!!#� &$ /� ��* ���+. �0 % �&$�! ) 0 ��<#���� &��

8���&��! $% /�$) &��� (! +�"� + &�$�1 ���(#+��" &��

)$(��#(�! ���)�� ( !&�#�&#��1 ) !!1 !#*��'�� ( &�2&#��1

*$�$!�&01 *$�� +�)��!�$�!1 !�9� �+ !� *� $% &�� �)*( �&1

!�&� $% �)*( �& &�$�1 �+ &�� )���$($�$)$&�$� $% *$(0)��

%� ")��&! & &�� ��&��% �� -�&� +A ���& &�!!#� 34�5.

�� ���(#!�$� $% *( !&���9�� �� *$(0)�� �� ��!

+���� !�! &�� ��&�� �&�$� )$�" &��) /#& ����� !�! &��

<�2�/�(�&01 *$�$!�&0 �+ +�"� + &�$� $% &�� *$(0)��

3441 4�5. �� &��! -$�81 -� �2 )���+ &�� /�$($"�� (

*�$*��&��! �+ +�"� + &�$� *�$��!! $% 6��� )�)/� ��!

�$�& ����" +�%%����& �$����&� &�$�! ��1 @ �+ 44B� $% &��

*( !&���9�� &���&�0(��&� &� �+ !!�!!�+ &���� ��&�� �&�$�

-�&� +A ���& &�!!#� �� ����.

� ���� �� �� ���������&(,!��$ �* � )��$!�6��� �C ��� ���� - ! *�$,�+�+ ! *�((�&! ��+!$�/

����$($"��! ��&��� &�$� ( �.6.1 ������� &�1 �D1 � ��.

�� "� )! $% *$(0)�� -��� +�!!$(,�+ �� 4��)� $%

)�&�0(��� ��($��+� ��D��(�1 ���8 E" �1 � �)!& +&1

F��) �0� �$�& ����" �B1 @B $� 44B &���&�0(��&� &�

��(+����1 �(- #8��1 C�1 � �� �� �($!�+ ����*���& &

�$$) &�)*�� &#��. �� )�2&#�� - ! &��� *$#��+ $� &$

"( !! *( &� �4�� �)��1 -���� - ! ��7+���+ � �� <$- $%

4 �G)��� & �$$) &�)*�� &#��. �%&�� 4� �1 &�� )�)/� ��!

-��� ��)$,�+ %�$) &�� *( &�! �+ , �##) +���+ %$� �� �.

H�#&�$� &$ -�$) (( �$���!*$�+���� !�$#(+ /� ++��!!�+.

�@�>����� � ���� ��� � ���� ��� ������ �� 689

��!�! �)) �� +� )�&�� �+ ��� �) &���8 -��� �#& �+

#!�+ �� &�� !&#+��! +�!���/�+ /�($-.

� )��$!�!��$�� )�)/� ��! -��� �))��!�+ �� >�B �&� �$( �+ &���

, �##) +���+. ��"�&��� %�) (� C�!& � � &! � )$�&�! $(+

$/& ���+ %�$) &�� #��,��!�&0;! ���&� ( ��) ( �$#!�

����=� -��� #!�+. �� � &! -��� �$#!�+ & ��� � ��$� 4� � (�"�&G+ �8 �0�(� -�&� %$$+ �+ - &�� �� ������.

-$ )�)/� ��! $% � �� *( !&���9�� �$����&� &�$� -���

�)*( �&�+ �� &�� +$�! ( !#/�#& ��$#! &�!!#� $% � �� � &

��� 4?� ��!&��&�9�+ -�&� 8�& )��� �+ 20( 9���7D�(

�4�.�)"G8" �+ �.��)"G8" �.*.1 ��!*��&�,�(0� �I��/ �1

�$!��� 1 J$ 6 #($1 =� 9�(�. �� �� (&� �+ /�� ,�$� $%

&�� � &! -��� !!�!!�+ + �(0 #�&�( ! )*(� �$((��&�$� & �1

4� �+ �� + 0! *$!&7�)*( �& &�$�.

��+"! �,���,�)'�� ")��&! $% !8�� -��� '2�+ �� =$#�� !$(#&�$� �+

�)/�++�+ �� * � %'� ����8�. ��&�$�! � �) &���8 -���

!& ���+ -�&� !!$�;! &�����$)� �+ !���#! ��+.

�)/� �� %� ")��&! &� & � + +����+ &$ +A ���&

&�!!#� -��� '2�+ �� �B * � %$�) (+��0+� � �")

���)�� ( �$.1 &. �$#�!1 �1 � �� �+ �)/�++�+ ��

"(0�$( )�&� ��0( &� ��!�� �E#(9��1 K-��"���+��( !!#�"1

C������)1 F��) �0�. ��&�$�! � �) &���8 -��� !& ���+

-�&� &$(#�+��� /(#�. ��!� ! )*(�! -��� $/!��,�+ �+

*�$&$"� *��+ -�&� ��8$� ��(�*!� �?�� *�$&$)���$7

!�$*�. �� ! )*(�! !& ���+ -�&� !���#! ��+ -��� $/!��,�+

�+ *�$&$"� *��+ #�+�� *$( ��9�+ (�"�& &$ !!�!!

��, !�$� /0 �$(( "�� '/��!.

�,�$$�$+ ���,!��$ �,���,�)' -���. )*(�! %�$) &�� +�%%����& *���$+! $% �)*( �& &�$� -���

'2�+ �� �.�B * � %$�) (+��0+� � �") � �+ �.�B

"(#& � (+��0+� ��(��&�$� ���$!�$*0 ������1

C !���"&$�1 6�1 � �� �$�& ����" �.�B & ���� ��+

� �") � �� �.4 *�$!*� &� /#%%��1 *D >.�1 %$(($-�+ /0

*$!&7'2 &�$� �� 4B $!)�#) &�&�$2�+� � �") � �� &��

! )� /#%%��. �%&�� +��0+� &�$� �� "� +�+ �&� �$( !����!1

&�� ! )*(�! -��� %���9�7%� �&#��+ �� (�L#�+ ��&�$"�� &���

���&�� ( *$��& +���+ ��6� ���1 = (9��!� �+ !*#&&���+

-�&� "$(+ � �� ���1 = (9��!�. �� ! )*(�! -���

�2 )���+ �� ��$( � �?�� �I !� ����" �(��&�$�

)���$!�$*� �� * ��.

��������$ !�"�! $% !&�$�" ��< )) &$�0 *�$��!!1 !#�� ! �

����� !� �� ($� ( /($$+ <$-1 �+�) 1 /(#!� $� ����$!�!

-��� !��� +#���" &�!!#� ! )*(��". �� )�)/� ��! -�&�

)$�� *( !&���9�� �@B �+ 44B� +����+ )$�� &$ &��

+A ���& &�!!#�1 -���� ! &�$!� -�&� �B *( !&���9�� � !�(0

+�& ���+ %�$) �&. � ����" �(��&�$� )���$!�$*0 � ��

� (0!�! $% )�)/� ��! �$& �)*( �&�+ ��,� (�+ +�%%����&

!�9� *$��! +�(�)�&�+ /0 "($/#( � #��&! $% &�� -���8(�+

!#�% ��. �2 )�� &�$� $% &�� *$(0)�� %� �&#�� !#�% ��

!�$-�+ &� & &�� )�)/� �� % ��! +�%%���+ �� *$�$!�&0

���". 4�. �! &�� )$#�& $% *( !&���9�� ����� !�+1 &�� *$��!

�2&��+�+ +��*�� �+ &�� *$�$#! �� /�� )� &���8�� &� �

&�� +��!� �� �$% ($- *$�$!�&0� !$ &� & �� ! )*(�!

�$�& ����" 44B *( !&���9�� �& - ! �$& *$!!�/(� &$

+�!&��"#�!� �$�7*$�$#! % �� ���". ��.

��+"! �,���,�)'��+�*��+��&(0 $% &�� *�����& "� $% *( !&���9��1 &-$ + 0!

%&�� �)*( �& &�$� &�� ! )*(�! !�$-�+ &�� &0*�� (

%� &#��! $% �#&� *� !� ��< )) &�$�1 ���(#+��" ��#7

&�$*��( ��'(&� &�$�1 '/��� ��&! �+ !$%& &�!!#� �+�) ���"!.

� �+ ��. �� &�� ���$��� *� !� �4� �+ �� + 0! %&��

�)*( �& &�$��1 '/�$#! � *!#(� %$�) &�$� �$#�+ &��

�)*( �& �+ ��, !�$� $% &�� *$��! /0 , !�#( � �$����&�,�

&�!!#� �+ "� �& ��((! -��� $/!��,�+ ���"!. � �+ ��.

)*(�! �$�& ����" �B *( !&���9�� ��& ���+ +��!�

!*��& �� + 0! %&�� �)*( �& &�$�1 -���� ) +� ��((#( �

��, !�$� �+ +��!�$� &$ +A ���& &�!!#� +�%'�#(&.

�2 )�� &�$� #�+�� *$( ��9�+ (�"�& ��,� (�+ /�� 87#* $%

&�� �)*( �&1 -�&� &�� %� �&#�� �� /���" ��, +�+ /0

�$(( "�� '/��! *�$���+��" $% &�� � *!#(� ���". >�. ��

! )*(�! �$�& ����" @B *( !&���9�� &���� - ! � ��&��!�

*���&� &�$� $% /($$+ ,�!!�(! &��$#"� &�� )�)/� �� *$��!

���". ?�. 6$( ��9�+ (�"�& !�$-�+ �2&��!�,� ��, !�$� /0

�$(( "�� '/��! %�$) &�� � *!#(� ���". @�. C�&��� 4� + 0!

$% �)*( �& &�$�1 ! )*(�! �$�& ����" 44B *( !&���9�� -���

��, +�+ /0 ( �"� )$#�&! $% �$����&�,� &�!!#� �+ -���

!#��$#�+�+ /0 � *!#(� ���� �� /($$+ ,�!!�(! ���". 4��.

����� � �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� �B *( !&���9��

/�%$�� �)*( �& &�$�. �$&� &� & &���� �! $�� *$�$#! % �� �+ �$&��� -�&�

+��!�� !&�#�&#��.

����� � �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� 44B

*( !&���9�� /�%$�� �)*( �& &�$�. �$&� &�� �$)*(�&�(0 *$�$#! !&�#�&#��.

686

�%&�� �� + 0!1 &�$!� �)*( �&! -��� �$,���+ -�&� &�!!#�

���". 44�.

�,�$$�$+ ���,!��$ �,���,�)' � *�$,�+�+ (�&&(� ��%$�) &�$� /$#& &�� &�!!#�

�$)*$���& !���� -�&� &��! &�����L#� �& �! �$& &$ *$!!�/(�

+�!&��"#�!� )$�" +�%%����& &0*�! $% ��((!. D$-�,��1

� *�$,�+�+ "�� &�� ��!�"�& ��&$ &�� *$��! $% *$(0)��

+�"� + &�$�.

-$ + 0! %&�� �)*( �& &�$�1 -��� &�� +�"� + &�$�

*�$��!! � + �$& 0�& !& �&�+1 �#&� *� !� ��((! �+ '/���

��&! -��� !��� &��$#"� &�� )�)/� �� *$��! ���". 4��1

��+�*��+��&(0 $% &�� )$#�& $% *( !&���9�� #!�+. �$#�&���

+ 0! %&�� �)*( �& &�$�1 &�� *$(0)�� #��&! $% )�)/� ��!

�$�& ����" �B �+ @B *( !&���9�� -��� !&�(( ��& �&.

����� 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� @B *( !&���9�� ��

+ 0! %&�� �)*( �& &�$�. ���� �! � �2&��!�,� ��'(&� &�$� $% /($$+

,�!!�(! � ��$-!� &��$#"� &�� *$(0)�� *$��!.

����� � 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� @B *( !&���9��

&-$ + 0! %&�� �)*( �& &�$�. �/!��,� &�� *��!���� $% '/��� ��&! �H� �+

&�� ( �"� �#)/�� $% ��#&�$*��(! � ��$-!� ��!�+� &�� *$(0)�� *$��!. ��

� *!#(� ��� �! �� &�� ���&� ( !& "�! $% %$�) &�$�.

����� ! 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� @B *( !&���9�� ��

+ 0! %&�� �)*( �& &�$�. �$&� &�� *��!���� $% &�� '/�$#! � *!#(� ��� �+

"� �& ��((! � ��$-�. ���� �! (!$ � ��'(&� &�$� $% /($$+ ,�!!�(!

� ��$-�� +� �+ �$����&�,� &�!!#� �H�.

����� " 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� 44B *( !&���9��

&-$ + 0! %&�� �)*( �& &�$�. �$&� &�� , !�#( � �+�) ��� �+

��#&�$*��(! �H� ��!�+� &�� *$(0)��.

����� # 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� �B *( !&���9�� ��

+ 0! %&�� �)*( �& &�$�. �� )�)/� �� �! !�* � &�+ %�$) &�� +A ���&

&�!!#� �H� �+ �! !&�(( +��!�1 -�&� ($- *$�$!�&0.

����� $ 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� �B *( !&���9�� ��

+ 0! %&�� �)*( �& &�$�. �$&� &�� �#*&#�� ��"�$� $% )�)/� �� /���"

��, +�+ %$� ) �0 �$(( "�� '/��! %�$) &�� � *!#(� ���.

68:

�(&�$#"� �� &�� @B ! )*(�! &���� - ! "�� &�� ��((

��'(&� &�$�1 -�&� !$)� $% &�� ��((! +�����" '�)(0 &$ &��

*$(0)�� !#�% �� ���". 4��. �� ! )*(�! �$�& ����" 44B

*( !&���9��1 &�� ���&� &�$� $% *$(0)�� +�"� + &�$� - !

$/!��,�+ %&�� 4� + 0!1 -�&� &�� **� � ��� $%

���&��%#" ( %� �&#��! �� &�� )�)/� �� #��&! ���". 4��.

�2&0 + 0! %&�� �)*( �& &�$�1 &�� ! )*(�! �$�& ����"

�B *( !&���9�� ��) ���+ +��!�1 -�&� (�&&(� ��, !�$� /0

&�!!#� �(�)��&!1 (&�$#"� !$)� "($/#( � #��&! !�$-�+

!�"�! $% +�"� + &�$� ����&��%#" ( %� �&#��!� ���". 4��.

�%&�� �� + 0!1 �)*( �&! �$�& ����" @B �+ 44B

*( !&���9�� -��� �� � +, ���+ !& &� $% +�"� + &�$� ��

-���� &�� *$(0)�� #��&! -��� �2&��!�,�(0 +�!�#*&�+ �+

�))��!�+ �� ( �"� )$#�& $% �$����&�,� &�!!#� ���". 4��.

����� �� 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� 44B *( !&���9��

�� + 0! %&�� �)*( �& &�$�. �$&� &�� &���8 � *!#(� ��� �+ &�� &�!!#�

��, !�$� � ��$-�� +!� &� & �,��&# ((0 (� +! &$ !�* � &�$� $% &�� *$(0)��

#��&!.

����� �� �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� �B

*( !&���9�� &-$ + 0! %&�� �)*( �& &�$�. ��/��� ��&! � ��$-�� +!� �+

��< )) &$�0 ��((! �� *��!��& � ��$-!�.

����� �� �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� @B

*( !&���9�� 4� + 0! %&�� �)*( �& &�$�. �$&� &�� *��!���� $% ��((

'�)(0 +����+ &$ &�� *$(0)�� !#�% �� � ��$-�. �� )�)/� �� #��&! +$

�$& !�$- %� �&#��! & &��! !& "�.

����� % 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� @B *( !&���9�� ��

+ 0! %&�� �)*( �& &�$�. 6$( ��9�+ (�"�& !�$-! *$�� ��, !�$� /0 �$(( "��

'/��(! � ��$-!� %�$) &�� � *!#(� ���.

����� �� 6�$&$)���$"� *� $% 6��� )�)/� �� -�&� 44B *( !&���9��

4� + 0! %&�� �)*( �& &�$�. �$&� &�� '/�$#! � *!#(� ��� -�&� ) �0 /($$+

,�!!�(! � ��$-�� +!� !#��$#�+��" &�� �)*( �& �+ &�� ��&��!�

�$����&�,� &�!!#� ��'(&� &�$� �H�.

����� �" �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� 44B

*( !&���9�� 4� + 0! %&�� �)*( �& &�$�. �� "($/#( � #��&! $% &��

)�)/� �� !�$- &�� &0*�� ( ���&��%#" ( %� �&#��! � ��$-!� $% &��

+�"� + &�$� *�$��!!.

68;

�������������$�+��" &$ ���(7I �(�& � �. 34�51 &�� ��< )) &$�0

��!*$�!� &$ /�$) &��� (! �! +�&��)���+ /0 &�� �$)*$!�7

&�$�1 *#��&01 �$�%$�) &�$�1 !#*��'�� ( *�$*��&��!1

�)*( �& &�$� !�&�1 *$�$!�&01 ���)�� ( !&�#�&#��1 �+

$&��� *�$*��&��! $% &�� ) &��� (. �� &�� � !� $% /!$�/ /(�

*$(0)��!1 &��!� % �&$�! (!$ ��<#���� &�� �2&��& $%

+�"� + &�$� /0 &�!!#�. �� &�!!#� �� �&�$� &$ 6��� - !

��<��&�+ /0 &�� *��!���� $% '/�$/( !&!1 ) ��$*� "�!1

"� �& ��((! �+ *$(0)$�*�$�#�(� � ��((!.

�� &0*� $% ��< )) &$�0 ��!*$�!� &$ 6��� �)*( �&!

+�*��+�+ $� &�� &�)� !���� �)*( �& &�$� &�)� � &��� &� �

$� &�� �$����&� &�$� $% *( !&���9��1 (&�$#"� �)*( �&!

-�&� �$�& ����" ��"��� $% �$����&� &�$� *( !&���9��1 � +

"�� &�� *$�$!�&0 �+ )$�� ��&��!� ��(( ��!*$�!�. ��

�#&� ��< )) &$�0 �� �&�$� - ! !��� �� (( &�� ! )*(�!

$/& ���+ &-$ + 0! %&�� �)*( �& &�$� �+ ��<��&�+ &��

($� ( !#�"�� ( &� #) . #/!�L#��&(01 ���$��� �� �&�$�

- ! $/!��,�+ �� ��!*$�!� &$ &�� �)*( �&. �� &��! ���$���

*� !�1 &�� %$�) &�$� $% '/�$#! � *!#(� �$#�+ &��

)�)/� �� �+ &�� *��!���� $% "� �& ��((! !#""�!&�+ &� &

&�� $�" ��!) - ! &�0��" &$ �!$( &� �+ /!$�/ &��

�)*( �&. �� ��, !�$� $% &�� )�)/� �� /0 , !�#( �

�$����&�,� &�!!#� ��+�� &�+ &� &1 �� ++�&�$� &$ !&�)#7

( &��" &�� ��< )) &$�0 �� �&�$�1 &�� )�)/� �� (!$

��� ���+ ��"���� &�$� $% &�� + ) "�+ &�!!#�.

6��� �)*( �&! +�,$�+ $% *( !&���9�� +$ �$& � ,� *$��!

34�5 �+1 �$�!�L#��&(01 +$ �$& (($- ��((#( � ��, !�$�.

�� ++�&�$� $% *( !&���9�� *�$,�+�! ) ((� /�(�&0 �+

*$�$!�&01 �+ )$+�'�! &�� &�!!#� �� �&�$� &$ &�� �)*( �&.

�! !�$-� ����1 &�� "�� &�� )$#�& $% *( !&���9�� ++�+1

&�� "�� &�� �)*( �& *$�$!�&01 ��((#( � ��, !�$� �+ !*��+

$% +�"� + &�$�.

���$�+��" &$ �#�� �$ � �. 34�51 &�� *( !&���9��

�� �"�! &�� )$�*�$($"0 $% )�)/� ��! +� !&�� ((0. ��!

� � /� �2*( ���+ /0 &�� ��&�� �&�$� $% *( !&���9�� -�&�

)$�*�$#! ��"�$�! $% *$(0)�� *�$,$8��" &�� !�* � &�$�

$% &�� *$(0)���� �� ��!. $��$,��1 &�� *�$��!! $% &��

%$�) &�$� �! % ��(�& &�+ �+ ��!#(&! �� &�� %$�) &�$� $%

!*���#(�&�� !&�#�&#��!. �� ""($)�� &�$� $% &��!�

!*���#(�&�� !&�#�&#��! � #!�! &�� %$�) &�$� $% �

��&���$����&�+ *$�$#! !#�% �� +#� &$ &�� ++�&�$� $%

*( !&���9��. �� #&�$�! ,���'�+ &� & &�� �($�" &�$� #�&�(

�#*&#�� ����� !�! -�&� &�� ++�&�$� $% *( !&���9��1 -����

��+�� &�! ��"��� <�2�/�(�&0 $% &�� )�)/� ��!. ��! + &

- ! �$�'�)�+ /0 &���) ( � (0!�! !�$-��" &� & &�� "( !!

&� �!�&�$� &�)*�� &#�� +���� !�! -�&� ++�&�$� $%

*( !&���9�� 34�5.

�� )�)/� ��! �$�& ����" �B *( !&���9�� � + ,��0

+��!� !&�#�&#��1 -���� ���+���+ &�� &�!!#� ��, !�$� �+

, !�#( ��9 &�$� $% &�� �)*( �&. ��!� )�)/� ��! -���

#� /(� &$ ��$))$+ &� &�� � &#� ( ) ((� /�(�&0 $%

!#/�#& ��$#! &�!!#�1 �+ �� !$)� ! )*(�! &��0 �,��

&$��. #�� )�)/� ��! ) 0 /� #!�%#( �� "#�+�+ &�!!#�

��"���� &�$� $� $&��� &�����L#�! $% ���#*�� &�$� &� &

��L#��� &�!!#� �!$( &�$� &��$#"� &���8 )�)/� �� -�&�

($�" +�"� + &�$� &�)�.

�� �$�&� !&1 )�)/� ��! �$�& ����" @B �+ 44B

*( !&���9�� -��� )#�� )$�� *$�$#! �+ ) ((� /(�.

�� *��!���� $% /($$+ ,�!!�(! �� &��!� ! )*(�!

!#""�!&�+ '�!& !&�* &$ ��$, !�#( ��9 &�$�1 -�&�

��"���� &�$� &�� + ) "�+ &�!!#� �+ *��%��& *$(0)��

��&�"� &�$� ��&$ &�� !�&� $% �)*( �& &�$�. ��!�

)�)/� ��! -$#(+ /� )$�� ��+�� &�+ %$� !$%& &�!!#�

��"���� &�$� $� ! !#**$�& %$� �#(&#��+ ��((!1 -����

&�� &�!!#� ��*$!�&�$� �! % !&��. ��!� )�)/� ��! ) 0

/� /���'�� ( �� &�!!#� ��"�������" /�� #!� �& -$#(+

(($- ��"��� �#)/�� $% ��(( &$ /� �#(&�, &�+ �� &��

*$(0)�� )$(+1 �& -$#(+ % ��(�& &� &�� +�%%#!�$� $%

% �&$�! )$�" &� �!*( �&�+ ��((! �+ +A ���& &�!!#�

�+ -$#(+ �$�&��/#&� &$ &�!!#� , !�#( ��9 &�$� 34�5. ��

�$)* � &�,� !&#+0 $% *$(0)��! -�&� +�%%����&

+�"� + &�$� %� &#��!1 ��(�, �& &$ � �&�( "� ���$�!&�#�7

&�$�1 �$&��� � �. 34�5 �$��(#+�+ &� & *$(0)��

!#**$�&! -�&� !�$�&�� +�"� + &�$� &�)� -��� )$��

**�$*�� &� %$� %$�) &�$� $% &�� � �&�( "� ) &��21

-��(� *$(0)��! &� & -��� )$�� !& /(� ** ���&(0

����/�&�+ ) &��2 *�$+#�&�$�.

� �$�'�)�+ &� & )�)/� ��! -�&� )$�� *$��!

+�"� +�+ )#�� L#��8��1 *�$/ /(0 /�� #!� $% &�� "�� &��

��((#( � ��'(&� &�$� �+ �$�!�L#��&(0 "�� &�� * �&���* 7

&�$� $% ��((! �� &�� *$(0)�� +�"� + &�$� *�$��!!.

= !�+ $� &��!� ��!#(&!1 -� �$��(#+� &� & &�� ++�&�$�

$% &�� *( !&���9�� &���&�0(��&� &� &$ 6��� )�)/� ��! � �

/� #!�%#( %$� *�$+#���" �)*( �&! -�&� +�%%����& +�"� + 7

&�$� &�)� %$� , ��$#! **(�� &�$�!. �� �$����&� &�$� $%

*( !&���9�� %%��&! &�� *$�$!�&0 �+ ) ((� /�(�&0 $% &��

�)*( �&! -�&�$#& �$)*�$)�!��" /�$�$)* &�/�(�&0 $% &��

*$(0)��.

����� �! �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� �B

*( !&���9�� �� + 0! %&�� �)*( �& &�$�. �� *$(0)�� !�$-! !$)� !�"�!

$% +�"� + &�$� � ��$-!�. �(&�$#"� &�� )�)/� �� �! !&�(( +��!�1 !$)�

/�� 8! �� *��!��& �H�.

����� �# �(��&�$� )���$"� *� $% 6��� )�)/� �� -�&� @B

*( !&���9�� �� + 0! %&�� �)*( �& &�$�. �$&� &�� �2&��!�,�(0 +�"� +�+

)�)/� �� #��&! � ��$-� �+ &�� /#�+ �& &�!!#� ��, !�$� �H�.

68<

����������������! -$�8 - ! !#**$�&�+ /0 ��6� 6 �@?G4���@7�1 @?G

4��>�74 @@G4�@4?7� �+ @@G�@>��7��. �� #&�$�! &� �8

&�� �(��&�$� ���$!�$*0 � /$� &$�0 ��.=.1 �����6�

%$� #!� $% &���� % ��(�&��! �+ �. = (& 9 � 6����� +�

6 #( %$� &������ ( !!�!& ���.

����������4. � . � . ������� �+ � . � . � 6�� 1 &����� ���� �� ������

����.

�. � . =��� �M 1 ��' ( ����' ����' �� �4@@?� 4�@.

�. � . . 6 ����� 1 . =�N ��F 1 � . 6. � �� �F �+ .

F�F���C E � 1 �' &��� �' ���' ) �' �� �4@@�� �?�.

�. . I���� 7��F �O 1 � . � . F������1 . F���� 1 . I.

��=��J � 1 � . I. ��F�� 1 � . � . �� ��� 1 � . � . ����� ��

�+ � . �� ���O � 1 ����' �� �4@@?� ���.

�. E . E�C�� 1 . �K�E � 1 P. �=�� 1 P. �E��� �+ P.

� � D ���� 1 &����� ���� �� ������ �?@.

�. � . � . ����� �+ F . I����E 7��I�E�I �� 1 ���' (���' ( ��') �' �� �4@@?� 4�.

>. � . ���F�� �+ � . 6. I���� � 1 ��� �� �� �4@@�� @��.

?. = . 7 . E � �+ � . � . ����P1 *� ��� &��� ����' �� �4@@?�

���.

@. E . D . ��1 � . . �D�E������ 1 D . � ��=��FF� 1

� . �� � � �� �+ 6. � ���C��D�� 1 �' &��� �' ���' ) �' ��4@@�� 4��@.

4�. F . � . =���� 1 � . � . I�� =� ��� C� �E �+ . 6���� 1

&����� ���� �� �4@@�� ��4.

44. � . �D�F�� 1 � . F����� �� 1 � . � ���� 1 6. D .

�P �� 1 6. ������ 1 � . �� �� 1 = . ��F���F� �+

F . ����� 1 �' &��� �' ���' ) �' �� �4@@�� 4��@.

4�. � . . ��� ���� �� :: QO�&�!�1 � � �&���9 �R J$ � ��"� + �R J$ +�

�)/� � ! +� 6$(�� O��+$ ( O&��$�1 #) *$(QO)��$ /�$ /!$�,QO,�(;;1

�����61 !&��! +�!!��& &�$�1 4@@>.

4�. 6. � �� �� 7I����1 . F�F���C E� �+ 6.

� � ��C��D�� 1 �' ���' ���' ���' � �' �4@@�� >4�.

4�. � . . ��� ���� �� ::�%��&$! + �$����&� �R J$ +� 6( !&�'� �&� �)

�)/� � ! +� 6$(�� O��+$ ( O&��$� * � �)*( �&�!;;1 �����61

��!�!1 ���4.

4�. � . � . ����P1 � . �. =���C�� 1 � . 6. �D 1 � . 6. I���� �

�+ � . ���F�� 1 &����� ���� � �4@@�� 4�4>.

4�. � . ���� 1 � . � �F��� 1 � . ������ 1 D . 6����E 1 � .

D��� 1 F . =��� �� �+ . � ��F�� 1 �' &��� �'���' ) �' �� �4@@?� ��>.

) � �� � �� �������� ��� +� � �$ ,���� � ����

657

COPYRIGHT INFORMATION

TITLE: Use of triethylcitrate plasticizer in the production ofpoly-L-lactic acid implants with different degradationtimes

SOURCE: J Mater Sci Mater Med 14 no72 Jl 2003

The magazine publisher is the copyright holder of this article and itis reproduced with permission. Further reproduction of this article inviolation of the copyright is prohibited. To contact the publisher:http://www.springerlink.com/content/1573-4838/