1. No category

Tissue Engineering and Regenerative Medicine, Vol. 1, No. 2, pp 164-170 (2004)
Õ\¢^Õ
öªÒ»j šÏR \8 ’V¢ æº
HæJšÞ ææÚ~ *` 5 ª+
;¢ÁJ^¯Ášê^*
‚Îv ª¶"
Fabrication and Characterization of Pore Size Gradient Alginate
Scaffold by a Centrifugation Method
Il Kyu Park, Se Heang Oh and Jin Ho Lee*
Department of Polymer Science and Engineering, Hannam University, 133 Ojeong Dong,
Daedeog Gu, Daejeon 306-791, Korea
(Received Oct. 11, 2004; Accepted Oct. 15, 2004)
Abstract: It is well recognized that the pore size of scaffolds plays an important role for tissue ingrowth and regeneration: different kinds of cells were shown to have different optimal pore size ranges in the scaffolds for effective
cell growth. So, if the tissue scaffold with pore size gradient (i. e., the scaffold with gradually increasing pore sizes
along one direction) can be prepared, it will be of particular interest for basic studies of the interaction between tissue
cells and scaffolds since the effect of pore size can be examined in a single experiment using one scaffold (pore size
gradient scaffold). In recent years, several techniques have been used to fabricate porous polymer scaffolds having
3-dimensional pore structure. However, it is not possible to fabricate scaffolds with pore size gradient from those
techniques. In this study, we developed a new method to fabricate pore size gradient scaffolds by a simple centrifugation. We fabricated alginate cylindrical scaffolds with gradually increasing pore size (80~310 µm) along the longitudinal direction by the centrifugation method. In this method, the pore size ranges of the scaffold could be easily
controlled by adjusting centrifugal force. The prepared alginate scaffolds were impregnated into 1 wt% chitosan
solution to improve cell adhesiveness as well as mechanical strengths. This study demonstrate that the centrifugation
method is a simple and effective method to prepare tissue scaffolds with controllable pore size ranges.
Key words: Tissue engineering, alginate scaffold, pore size gradient, centrifugation method
1.
* V
‚ ’–f ;¢ æò ææÚ¢ B–‚ r, ^
j ææÚö š² ªÖ~ 6OÊ ÃÎ ê, ž
Ú Ú~ ö~º ¦*ö š~ î‚Ú –ç~ Òj F
ê~º ©š
. š‚ –çf ^~ Ò" ^
~ WËj ææš"º ªšW ææÚ¢ B–~º ¢š
Zí
7º~
. žÚ –ç~ Òj *šB ÒÏ>º
ææÚ Òò~ "B ºšf, –ç^& Òò ‚šö 6
O~ 3Nö ’–¢ &æº –çj ;W† > ®êƒ 8
î $º ææÚ~ †j Ϫ® šÚ¢ ~, ÚÚö š
B êöê "* –ç" [z& ¾ >Ú¢ ~– "à >
wš ì ¢; 8*š æ ê Êʂ ªš~ šbî
‚ Îæ pº Ö>‚ Ú'Wj &^¢ ‚
. *Ò 6
Ò ÒÏ> ®º W ª¶‚Bº ÒjžÖ, Ò
n~š¢š, Ò ε -š*‚£Ê, ÒJšþöÊrš, –皦 ~,  5 «" ~ 8 Bv
" 8Fj ۏ wÏ~ Ú –ç~ ’–f 8ËҚ~
ç&&ê¢ šš~ ¾j& ږçj ڞöB Ò~
ÚÚ~ ö¾ *~ö šŽb‚B ÖÒ Þ~ 8Ëj F
æ, Ëç 5 ö~º ©j Ï'b‚ ‚ î‚Ú wÏ^
ª¢š
. ¶çB –ç~ öj *‚ –ç~ ¢>
'ž 7 O»f, ²ï~ –çÞb‚¦V jº‚ ^¢
ºÂ ªÒ‚ r ^V·j Û~ Ϫ‚ ·b‚ Ã
5 ªzÊ, Ú '‚ ªšW Òò¢ šÏ~ '
7
1-6
*Tel: 042-629-7391; Fax: 042-629-8841
e-mail: [email protected]
164
öªÒ»j šÏR \8 ’V¢ æº HæJšÞ ææÚ~ *` 5 ª+
–, š
~ ΂æ, ’V, ê 5 Vê' >Wj
jv ï&~&
.
Ò&ÒRÖ, Ò£Ö 5 š
~ 7Úž Ò£&ÒR֚ ®b– ,  ªšW ª¶‚º ræJ
šÞ , ÊÆÖ Ò R¢¶ š ®
.
š‚ ª¶¢ W ’–‚ ò
V *‚ O»
š ê> ®º– W ª¶~ ãÖöº ª¶¢
Ϛ~ ®º χö ¢;‚ ’V~ Ö; ².j b
~ š–‚ ê ².j Ϛ* ºÂšÚº » , &Ê
¢ ÒÏ~ ª¶¢ ccʺ » , ª¶ RF¢
¦ç‚ ò
Ú z’ ;‚ B–~º » , ª¶ χ
ö ŽF>Ú ®º Ï
¢ jÏ
³ö ’Ú çªÒÊ
º » , ª¶¢ ϚΠχ" >j b~ Fz Ï
‡b‚ ò ê ‡Ú ïÿÊ ÿÖ š–~º »
, š ®
. š
O»j šÏ~ W ª¶ ææ
Ú¢ òº– ®Ú J~¢ † 7º‚ ©
7 ~¾
& ’V 5 êš
. ¯, ž ^žVî $º
^ ææڂB ^~ ¦OWš ± '·/" ö‚
‚ &Ò·Ïj ò—Ò > ®º ê¢ æò ’–šÚ
¢ ‚
. ææÚ~ êº ææÚ~ >Wö – æËj
.¾~æ pº ‚ š>ƒ F҂ ©b‚ rJ^ ®
. $
‚ ’V& š>ƒ '·/" &Ò·Ïöº F҆
> ®b¾ ^~ ¦OW (¦O&ê)š 6²~ ^ W
˚ ÚJÞ > ®b–, ’V& ·j>ƒ '·/
" &Ò·Ïöº ®Ò~æò ^& ¦O~Vöº F҆
> ®
> ®
.
­­ ’¶
ö ~š ^~ WËö ‚'ž ’V
º ^î
–.O Nš& ¾º ©b‚ >Ú ®b¾,
jçræ šö &‚ Úê'ž ’º ‚ ;š
. V¢B ^~ ¦OW" '·/ 5 &Ò·Ï, š v
&æ –šj ò—ʺ ’V~ ‚'z ’º –ç
^~ âNö V· 5 –çÒö 7º‚ ¢ † >
®
. ÿn –ç^~ «~ö Vž, ’V~ ‚'
–šj {ã~V *š ¢>'b‚ ’V& B‚ ž
ææÚ¢ '' B–~ ÒÏ~&
. ~æò, ~¾~ ææ
Ú ò ÚöB ’V& 6ê'b‚ æz‚
š, ’V& B‚ ž ææÚ ò
j V‚V‚ &jš¢
>º ®–‚æj ‚, ''~ ò
j êê‚ &j~º
"; 7ö ^ > ®º þJNê R *¢ >& ®
Ú, ææÚ~ ’Vö Vž –ç~ ¦O 5 WË –
ÿj Úê'b‚ ’~ ‚'z~º– ç® ÎN'š
¢ † > ®
. V¢B ’öBº, ’&š n
‚ âNö W ª¶ ææÚ B– O»ž öªÒ»
(centrifugation method) j wÏ~ ’V ’V¢ &
æº Öz η~ ræJšÞ ææÚ, ¯ Öz » O
Ëb‚ ’V& 6ê'b‚ Ã&~º ææÚ(pore size
gradient scaffold)¢ B–~, š ææÚ
~ >W ;zf
^ ‚zW Ëçj *š ÊÆÖb‚ ŽŽÁê ~&b
8
9
10
11
2.
Òò 5 O»
þ Òò. W ææÚ¢ B–~8 *‚  ª
¶‚B, š–~öB ºÂB ræJšÞ(alginic acid sodium
salt; medium viscosity; Sigma Chem. Co., St. Louis,
MO, USA)¢ 65% zêR‚ >² ^¿~ çNöB ê
š–~ ÒÏ~&
. ræJšÞ~ &vB‚º CaCl
(Oriental Chem. Ind., Korea)¢ ÒÏ~&
. $‚ B–B
W ææÚ~ >W" ^6OKj ËçÊ8 *š Ê
ÆÖ (low molecular weight; Fluka, Switzerland)j ÒÏ
~&
.
’8 ’8¢ æº HæJšÞ ææÚ~ *`. W ræJšÞ ææÚ¢ B–~8 *‚ * ê‚B, š
& ·šNö ~š &vB RFFÒç~ ræJšÞ¢ B
–~&
. š¢ *š 2 wt%~ CaCl χj 500 mL j
š
ö , š χj ^β¾š& (HG-3000, SMT,
Japan)¢ šÏ~ 24,000 rpmb‚ ;~² v>~šB 2
wt%~ ræJšÞ >χj ® ÎÚNJ "î
. š "
;j ۚ RFFÒç~ &vB ræJšÞ& ;W>–, š
f "¢ ۚ CaCl χj B–~, .B>¢ šÏ
~ ^¿Á" ";j 2² >~&
. W ææÚ
~ B–¢ *š, *öB B–B RFFÒç~ &vB r
æJšÞ& >χ Úö ¾ ªÖ>êƒ ¶Cv>8¢ š
Ï~ v>~ & r, š >χj Ò*‚j2(PP)
Òî~ ¸š 85 mm, çã 14 mm~ :š ïï‚ Ö
z; :šrö & jÚ ê, öªÒ8(Marathon 21K,
Fisher Scientific, USA) Úö *~Ê ¢;‚ ²*³ê
(1,000, 2,000, 5 3,000 rpm)‚ 5ª* öªÒ~&
. ç
[‡j –Ê#² B–‚ ê, :šr Úö '[B RF
FÒç~ ræJšÞ¢ -76 C~ ïÿš–8(NU-6617D34,
Nuaire, USA) ÚöB ÿÖÊ, ÿÖB ræJšÞ¢ Ž~ ®º :šrj ïÿš–8(FDU-540, Eyela, Japan)
ÚöB ÿÖ š–~ :šr~ ¸š OËb‚ ’8
& 6ê'b‚ æz~º Öz; ræJšÞ ææÚ (ç
ã~14 mm, ¸š~5 cm)¢ B–~&
. (Figure 1)
ÊÆ֚ ê* 9 HæJšÞ ææÚ~ *`. B
–B W ææÚ~ >W" ^6OKj ËçÊ8 *
š ræJšÞ ææÚ Úö ÊÆÖj ŽŽ, ê~ "
î
. ÊÆÖf >öº Ϛ>æ p ÖWχöB Ϛ
>æ‚, 0.1 M .Öj ÒϚ 1 wt%~ ÊÆÖ >χ
j B–~&
. „öB B–‚ W ræJšÞ ææÚ
¢ ÊÆÖ >χö 30ª* ŽŽB "î
. ŽŽB Ê
ÆÖf ræJšÞf ÊÆÖ~ šNÚö ~š ræJ
12,13
14,15
16
25
2
17
18
19
2
2
1,20,21
1,22,23
o
24
26
165
;¢ÁJ^¯Ášê^
VB, W º G;~¶ ~º ææÚ~ Z², W f ö
êRj & jÚ j7÷~ Z², W º ææÚf öêR
š & jòê j7÷~ Z², Ò W º W ‚¦8 ö
êRš ŽFB (ææÚ~ ö öêRš jòê ç) æ
æÚ¢ âÞ ê j7÷~ Z²¢ ¾æÞ
. ''~ Z²
¢ G;~ *~ êÖö ê«~ ê¢ êÖ~&
.
8ê >9 ï&. Vš~ Vê' bW G;O»b‚º
G;š ¾ ²; W ææÚ~ Vê' Wîj G;~
V *‚ Ë~¢ ’öB ç7 nÁB·~&b–, š
Ë~¢ Instron žËVV(AG-5000G, Shimadzu, Japan)ö
J~~ :ʒ; W ræJšÞ ææÚ~ š»žË
þj ¯~&
. (Figure 2) ææÚ~ Vê' bW G
;O»f r" ?
. :ʒ ;‚ B–>Úê W
ræJšÞ ææÚ (çã~14 mm, ¸š~5 mm)¢ Ö; ã Қö *~Ê ã~ ž¦ö Ë~>Ú ®º "Þ
‚ j*® ;Î ê, ç㚠6 mmž (ball) ;~
j &æº V
¦ /j ÒÏ~ 1 mm/min~ F³ê‚
š»žË þj ¯~&, š‚¦8 ~7-æ; Fj
’~&
.
s
1
2
3
Schematic diagram showing the fabrication of cylindrical
pore size gradient scaffold by a centrifugation method.
šÞ î ‚šö n;~² ;>º ©b‚ rJ^ ®
. šNÚ& ;WB W ææÚº phosphate
buffered saline (PBS, ~pH 7.4)b‚ 2² ^¿~ šN
Úö ~‚ êö ^~æ p îj jÖ ®º
ÊÆÖ >χj B–~, "ï~ .B>‚ 3² ^
¿‚ ê ÿ֚–~ ÊÆ֚ êB, ^V·ö '
‚ bWj &æº ææÚ¢ B–~&
.
ÎRæ ª+. B–‚ Öz; ræJšÞ ææÚ¢ »
OËb‚ 5 mm *Ïb‚ ¾¢ :ʒ ;‚ B–‚ ê,
' :ʒ~ î ; 5 ª¢ *¶*ã (SEM; S3000N, Hitachi, Japan)j ÒÏ~ &V~&, î~
’8º šæ ªCÊR (IMT, Korea)j šÏ~ ªC
~&
. $‚ ' :ʒ; ææÚ~ êº Archimedes'
öÒö 8.‚ j7÷ (Hubbard specific gravity bottle,
Hanil, Korea)j ÒÏ~ G;~&
. êÖf r"
?
.
27,28
3.
2
Ö # 8
9 HæJšÞ ææÚ~ ÎRæ # ê ª+.
ræJšÞº , î š–~öB ºÂ>º ~~ ¢«b‚B ÚÚ ëWš ì ªšWš–, º ;
W ËKš Ú ©b‚ rJ^ ®
. ræJšÞº βD-JšÞf α-L-&‚JšÞ *Ú
š 14 &Ò
zҚ ֏ö ~š ֏B ª¶ 7Ú‚B, Ca ,
Sr , 5 Ba " ?f 2& ·šN
" ;‚ ‚zKj
¾æÚÚ 2& ·šNš ŽFB >χ ÚöB ³® &
v֏~ ºj ;W‚
. šf ?f ë߂ Wîj &
ææ‚ ræJšÞº £b*Ú, ^ ;z 5 &ê
2+
2+
29
2+
30
Porosity (ε) = (W2-W3-Ws) / (W1-W3)
Photographs of biaxial tensile test equipment.
166
öªÒ»j šÏR \8 ’V¢ æº HæJšÞ ææÚ~ *` 5 ª+
V·, žb¦, –çÏ ææÚ Úª¢ö 6
Ò šÏ>Úæ ®
.
’öBº, W ææÚ B–ö „B RFFÒç
~ ræJšÞ¢ B–~¶ ræJšÞ >χ (2 wt%)
j CaCl >χ Úö BB® ÎÚNJ "šB ^β¾
š&¢ šÏ~ ;~² v>š ", š ";öB R
FFÒç~ &vB ræJšÞ& ;WNj SEMj ۚ &
V>î
.(Figure 3) âöB š &vB ræJšÞ& R
Ff j݂ ;¢ ¾æÚ ®rj {ž† > ®º–,
šº ^β¾š&ö ~šB CaCl >χö Vž ³ê‚
²*~º ²Ïòš& ò
Úæ, Vö ÎÚNJæº r
æJšÞ >χš B*'b‚ ²Ïòš~ ²*OËb‚ ^
o~² ¾JNJ^ &v>V r^š
. $‚ ''~ ö
ªÒ ²*³êö V¢ B–>º Öz; ræJšÞ ææ
Ú~ ~ ’V ª& ¢öj &V† > ®îb–, ²
*³ê& 1,000, 2,000 5 3,000 rpmb‚ Ã&†>ƒ ’V ª& '' 180~325, 135~290 Ò 80~310
µm‚ 'š 9Úöj r > ®î
.(Figure 3) šº
²*³ê 5 ²*>ã (:šr~ j¾& ²*>㚠¢)ö
~š ¢æº öK Nö ~‚ 'Ëb‚ 'B
. ²
*³ê& æš öK Ã&ö ~š &vB RFç~ r
æJšÞ& –&~² '[>–, ÿ¢ ²*³êöBê
²*>㚠– :šr~ jÑ ¦ª~ ãÖ ç&'b‚ z
– öKš ·Ï~ &vB RFç ræJšÞ& –&~² '[>¾, ²*>㚠ç&'b‚ ·f :šr~
=¦ª~ ãÖ Ôf öKb‚ žš RFç ræJšÞ
& ‚ –&~² '[>V r^ö Öz; ræJšÞ æ
æÚ Ú ’V ª& ¢æ² B
.
’öBº ’V& –ç^ 6O 5 Ãö ~º 'Ëj Úê'b‚ –Ò~V *‚ ææÚ B–& Ï
'šæ‚, &˂ 9f '~ ’V¢ &æº, ¯
3,000 rpm~ ²*³ê¢ ææÚ B–~ ‚'–šb‚ F
;~ ææÚ~ ΂æ 5 bWï&ö šÏ~&
. ’V ’V¢ &æº ææÚ B–~ ‚' öªÒ ³
êž 3,000 rpm~ ²*³ê‚ B–B W ræJšÞ
ææÚ~ ’V ª¢ {ž~V *š, Öz; æ
æÚ¢ Öz~ » OËb‚ 5 mm *Ïb‚ .~&
. .B ' :ʒ; ææÚ ‚š
j SEMj ۚ &
V‚ Ö"¢ Figure 4ö ¾æÚîb–, šæ ªCʂ
j ۚ ªCB ’V~ ï8" ‚&ÞN¢ Figure
5ö êz~&
. Figures 4, 5 5öB š, Öz;
W ææÚ~ » OËb‚ jњöB =šb‚ R¢
.>ƒ ~ ’V& 80 µmöB 310 µm‚ 6ê'b‚ Ã
&>º ©j {ž† > ®î
.
šº „öBê Þ/~&š, Öz~ » OËb‚ ·
Ï~º öKš ¸šö V¢ 6²~² >Ú Öz~ =
¦ªb‚ .>ƒ ’V& 6ê'b‚ Ã&~º *ç
b‚ šš† > ®
. š Ö"‚¦V, ’V ’V¢
&æº ææÚ&, ’&š n‚ öªÒ»j šÏ
~ Ö ¶£² B– F > ®rj {ž† > ®î
.
š ææÚº RFFÒç~ ª¶
š B‚ ïB®º ;
‚ îš B‚ Öꂎ ^WËö j>'ž Ö
², '·‡~ R" 5 &Òbî~ Vš Ϛ‚ ;‚
³'b‚ Ö>Ú ®rj &V† > ®î
. ' :Ê
’; ræJšÞ ææÚ~ ê ª¢ Archimedes' ö
Òö V.~ G;‚ Ö", ’V G;öBf ?š
31-34
2
2
SEM photographs of alginate scaffolds prepared at different centrifugal speed (x 100; *, pore size determined by image
analysis).
167
;¢ÁJ^¯Ášê^
SEM photographs of top surfaces of sectioned alginate scaffolds along the longitudinal direction (x 100; *, position code
(1, 0~5 mm; 2, 5~10 mm; 3, 10~15 mm; 4, 15~20 mm; 5, 20~25 mm; 6, 25~30 mm; 7, 30~35 mm; 8, 35~40 mm; 9, 40~45 mm;
10, 45~50 mm)).
Pore size distribution of sectioned alginate scaffolds
Porosity distribution of sectioned alginate scaffolds
along the longitudinal direction.
along the longitudinal direction .
Öz; ææÚ~ jѦªöB =¦ªb‚ .>ƒ ê& ~82%öB ~93%‚ Ã&Žj &V† > ®îº–,
(Figure 6) š©ê $‚ Öz; ææÚ~ » OË ¸š
ö Vž öK Nšö ~š RFFÒç ræJšÞ~ '
[ &ê& ¢^B Z Ö"¢ '>Úê
.
8ê >9 ï&. ’V ’V¢ &æº Öz;
ræJšÞ ææÚ¢ Öz~ » OËb‚ 5 mm *Ï
b‚ .~ :ʒ ;‚ ò ê, š»žË þj
ۚ Vê' >Wj G;‚ Ö"¢ Figure 7(A)ö ¾æÚ
î
. âö ¾æ :f ?š Öz; ææÚ~ » O
ËöB jÑ ¦ªb‚ ÚJ.>ƒ Vê' >Wš ;z>
º ©j &V† > ®î
. öªÒ»b‚ B–>º æ
æÚº RFFÒç~ ræJšÞ& B‚ ïÎ '[>Ú ®
, Öz; ææÚ~ jÑ ¦ªb‚ ÚJ.>ƒ ’
V 5 ê& ·jöb‚ ææÚ ÚöB RFFÒç r
æJšÞ
~ '[ &ê& Ã&Žö V¢ ¾æ¾º .G
&˂ Ö"š
. ’öBº $‚ ’V ’V¢
&æº ræJšÞ ææÚ~ Vê' >W" ^‚zW Ë
çj *š ræJšÞ ææÚ Úö ÊÆÖj ŽŽ, ê
~ "î
. ÊÆÖf ÒҚ¢š~ ¢«b‚ ²¾ î
168
öªÒ»j šÏR \8 ’V¢ æº HæJšÞ ææÚ~ *` 5 ª+
ž† > ®î
. šº '[B RFFÒç~ ræJšÞ
š ÊÆÖ" šN Ú¢ ;W~8 r^ž ©bR $
B
. ÊÆÖ ê ¾Ò, êB ÊÆ֚ ræJšÞ æ
æÚ~ ’–¾ ’8öº –~ 'Ëj ~æ pº
º ©ê SEMj ۚ {ž† > ®î
.
4.
3Nö' W ææÚ~ ’8& ·‚ –ç ^
~ 6O" WËö ~º 'Ëj –Ò~8*‚ ê’
RB, ’8 ’V¢ &æº Öz η~ ræJš
Þ ææÚ¢ ’š n‚ öªÒ»j šÏ~ ¶
£² B–~&
. öªÒ ²*³ê¢ –.ŽbRB Ö
z; ææÚ Ú ’8 ª¢ –.† > ®îb–,
3,000 rpm~ ²*³êR B–~&j r, Öz » OË
~ jÑ ¦*öB = ¦*R .>S 6ê'bR ’
8& Ã&~&
(80~310 µm º*). $‚, B–‚ ræJ
šÞ ææÚ¢ ^‚zW  ª¶ž ÊÆÖ &³ê
χ (1 wt%)bR ŽŽ, ê®j r ÊÆÖ" RFFÒ
ç ræJšÞ *~ šNÚ ;WbR žš, ’8
~ æzìš 8ê' bWš ;zNj {ž† > ®î
. Ê
Æ֚ êB ræJšÞ ææÚ~ ^ 5 –ç‚zW
{žj *‚ in vitro ^V· þ" .j ÿb
þf *
Ò ê¯ 7ö ®
. ’öB B–‚ ’8 ’V
¢ <º ræJšÞ ææÚº ' –ç ^
~ 6O, W
Ë 5 –ç Òö :²ç‚ ’8 –šj {ã~8
*‚ 8.’ >¯ö Ö Î"'ž ê’RB ÒÏF >
®j ©bR 8&B
.
$Ò~ : š ¢^f 2003jê ‚“Fê‹Ò~ æ
öö ~~ ’>îbæR šö 6Òãî
. (KRF-
Load-displacement curves of sectioned alginate scaffolds
along the longitudinal direction; (A) non-treated, and (B) chitosan
treated.
Ö " ?f 7'~~ óîöB áÚæº Êj îj
^z~ áÚæº Â ª¶‚B, ^ ëWš ìb
`, Ú'W" ªšW öò jî¢ ^ 6O" Ã
j Ëçʺ ^‚zW >î‚ rJ^ ®
. ÖW
ç (<~pH 6.0)öB ÊÆÖ Úö ®º -NH ·ÏV& š
Nz>Ú ·šN Ú¢ ;W~æ‚ ræJšÞf ?f
ršNW ª¶f ;*V' ç^·Ïö ~š £² šN
Ú (ÊÆÖ~ -NH ·ÏVf ræJšÞ~ -COO ·
ÏV Қ~ šNÚ)¢ ;W† > ®
. ræJš
Þ ææÚ~ ãÖ, RFFÒç~ ræJšÞ& B® B
‚ ïÎ '[ò >Ú®º ’–¢ &æ ®bæ‚, ^
V·‡ ÚöB ¢¦ ¦Úæº *çj &V† > ®î
.
ÊÆ֚ êB ræJšÞ ææÚ~ ãÖ, Figure 7(B)
ö ¾æ :f ?š ÊÆ֚ ê>æ pf ræJšÞ
ææÚf ?f ãËWj † ®b` (
Öz; ææÚ~
jÑ ¦ªb‚ ÚJ.>ƒ ’V 5 ê& ·jö
ö V¢ ææÚ ÚöB RFFÒç ræJšÞ
~ '[
&ê& Ã&~ Vê' bWš ;zN), ÊÆ֚ ê>
æ pf ræJšÞ ææÚö jš 8ê' >Wš R Ë
ç>î (Figure 7(A)f jv), $‚ ^V·‡ ÚöB
ê *& ¦Úææ p n;>² ;¢ Fæ~º ©j {
35
2
2003-041-D00212).
−
+
3
Ö V
^^ò
27,28
1. S Yang, KF Leong, Z Du, et al., The design of scaffolds for
use in tissue engineering, Tissue Eng., 7, 679 (2001).
2. J Zeltinger, JK Sherwood, DA Graham et al., Effect of pore
size and void fraction on cellular adhesion, proliferation, and
matrix deposition, Tissue Eng., 7, 557 (2001).
3. JJ Yoo, Tissue engineering: Direction and goals. In: JJ Yoo and
IW Lee, eds. Tissue Engineering: Concepts and Applications, Korea Medical Publisher, 1998, pp. 37-44
4. R Langer, JP Vacanti, Tissue engineering, Science, 260, 920
(1993).
5. JA Hubbell, R Langer, Tissue engineering, Chem. Eng.
News, March 13, 42 (1995).
6. RM Nerem, A Sambanis, Tissue engineering: from biology
to biological substitute, Tissue Eng., 1, 3 (1995).
169
;¢ÁJ^¯Ášê^
matrix deposition, Tissue Eng., 7, 557 (2001).
23. TG van Tienen, RGJC Heijkants, P Buma, et al., Tissue
ingrowth and degradation of two biodegradable porous polymers with different porosities and pore sizes, Biomaterials,
23, 1731 (2002).
24. SH Oh, KR Seok, IK Park et al., Fabrication and characterization of variously shaped porous alginate scaffolds by a
novel centrifugation method, Biomater. Res., 7, 37 (2003).
25. Y Shirai, K Hashimoto, S Irie, Formation of effective channels
in alginate gel for immobilization of anchorage-dependent
animal cells, Appl. Microbiol. Biotechnol., 4, 342 (1989).
26. A Chenite, C Chaput, D Wang et al., Novel injectable neutral
solutions of chitosan form biodegradable gels in situ,
Biomaterials, 21, 2155 (2000).
27. SG Kim, GT Lim, F Jegal et al., Pervaporation separation of
MTBE (methyl tert-butyl ether) and methanol mixtures
through polyion complex composite membranes consisting
of sodium alginate/chitosan, J. Membr. Sci., 174, 1 (2000).
28. O Gåser ∅ d, O Smidsr ∅ d, G Skjåk-Br k, Microcapsules of
alginate-chitosan I. Aquantitative study of the interaction between
alginate and chitosan: Biomaterials, 19, 1815 (1998).
29. J Yang, G Shi, J Bei et al., Fabrication and surface modification of macroporous poly(L-lactic acid) and poly(L-lacticco-glycolic acid) (70/30) cell scaffolds for human skin
fibroblast cell culture, J. Biomed. Mater. Res., 62, 438 (2002).
30. TA Becker, DR Kipke, T Brandon, Calcium alginate gel: A
biocompatible and mechanically stable polymer for
endovascular embolization, J. Biomed. Mater. Res., 54, 76
(2001).
31. P De Vos, BJ De Haan, GHJ Wolters et al., Improved
biocompatibility but limited graft survival after purification
of alginate for microencapsulation of pancreatic islets,
Diabetologia., 40, 262 (1997).
32. G Klöck, H Frank, R Houben et al., Production of purified
alginates suitable for use in immunoisolated transplantation,
Appl. Microbiol Biotechnol., 40, 638 (1994).
33. IR Matthew, RM Browne, JW Frame et al., Subperiosteal
behaviour of alginate and cellulose wound dressing materials,
Biomaterials, 16, 275 (1995).
34. SA Thompson, Method of making a medical device from
ionically crosslinked polymer, US Patent, 5,650,116 (July
1997).
35. PR Klokkevold, L Vandemark, EB Kenney et al., Osteogenesis
enhanced by chitosan (poly-N-acetyl glucosaminoglycan) in
vitro, J. Periodontol., 67, 1170 (1996).
7. JA Hubbell, Biomaterials in tissue engineering, Biotechnology,
13, 565 (1995).
8. J. Kobn, Bioresorbable and bioerodible materials. In: BD
Ratner, AS Hoffman, FJ Schoen, JE Lemons, eds. Biomaterials Science: An Introduction to Materials in Medicine.
Academic Press, 1996, pp. 64-73
9. L Shapiro, S Cohen, Novel alginate sponges for cell culture
and transplantation, Biomaterials, 18, 583 (1997).
10. SV Madihally, HWT Matthew, Porous chitosan scaffold for
tissue engineering, Biomaterials, 20, 1133 (1999).
11. T Fujisato, T Sajiki, Q Liu et al., Effect of basic fibroblast
growth factor on cartilage regeneration in chondrocyte-seeded
collagen sponge scaffold, Biomaterials, 17, 155 (1996).
12. AG Mikos, AJ Thorsen, LA Czerwonka et al., Preparation
and characterization of poly(l-lactic acid) foams," Polymer,
35, 1068 (1994).
13. SL Ishanug-Riley, GM Crane, A Gurlek et al., Ectopic bone
formation by marrow stromal osteoblast transplantation
using poly(DL-lactic-co-glycolic acid) foams implanted into
the rat mesentery, J. Biomed. Mater. Res., 36, 1 (1997).
14. LD Harris, BS Kim, DJ Mooney, Open pore biodegradable
matrices formed with gas foaming, J. Biomed. Mater. Res.,
42, 396 (1998).
15. JJ Yoon TG Park, Degradation behaviors of biodegradable
macroporous scaffolds prepared by gas foaming of effervescent
salts, J. Biomed. Mater. Res., 55, 401 (2001).
16. AG Mikos, MD Lyman, LE Freed et al., Wetting of poly(llactic acid) and poly(dl-lactic-co-glycolic acid) foams for
tissue culture, Biomaterials, 15, 55 (1994).
17. C Schugens, V Maquet, C Grandfils et al., Polylactide macroporous biodegradable implants for cell transplantation. II.
Preparation of polylactide foams by liquid-liquid phase separation," J. Biomed. Mater. Res., 30, 449 (1996).
18. K Whang, CH Thomas, KE Healy, Novel method to
fabricate bioabsorbable scaffolds, Polymer, 36, 837 (1995).
19. LG Cima, JP Vacanti, C Vacanti et al., Tissue engineering by
cell transplantation using degradable polymer substrates, J.
Biomech. Eng., 13, 143 (1991).
20. TM Freymam, IV Yannas, LJ Gibson, Cellular materials as
porous scaffolds for tissue engineering, Progress Mater. Sci.,
46, 273 (2001).
21. FJ O'Brien, BA Harley, IV Yannas, et al., Influence of freezing
rate on pore structure in freeze-dried collagen-GAG scaffolds,
Biomaterials, 25, 1077 (2004).
22. Z Zeltinger, JK Sherwood, DA Graham et al., Effect of pore
size and void fraction on cellular adhesion, proliferation, and
170