珊瑚_胶原_重组人骨形成蛋白_2复合人工骨的异位骨诱导_英文_
第 12 卷 第 4 期 V o l. 12 N o. 4 医 学 研 究 生 学 报 1999 年 11 月 N o v. 1999 Jo u rn a l o f M ed ica l Po s tg radu a te
珊瑚ƒ胶原ƒ重组人骨形成蛋白22 复合人工骨
的异位骨诱导
张森林, 孟昭业, 寿柏泉, 许建辉, 杨 震
()南京军区南京总医院口腔科, 南京 210002
( ) 摘要: 目的: 评价珊瑚ƒ胶原ƒ重组人骨形成蛋白22 22复合人工骨的骨诱导活性。 方法: 将珊瑚ƒ胶原ƒ rhBM P
22 植入大鼠背部肌肉内, 以珊瑚胶原或珊瑚22 植入作对照。术后 1 周和 4 周取材, 通过组织学和计 ƒƒrhBM P rhBM P
算机图像分析评价其异位诱导成骨情况。 结果: 珊瑚胶原22 植入后 1 周, 在局部诱导软骨形成; 4 周, 形 ƒƒrhBM P
()成含骨髓的板层骨; 诱导成骨的量有明显的 22 剂量依赖性 < 0. 001。珊瑚ƒ胶原或珊瑚ƒ22 植入区rhBM P P rhBM P 无骨或软骨形成。 结论: 珊瑚胶原22 复合人工骨具有良好的异位骨诱导活性, 是一种较理想的骨移植替 ƒƒrhBM P
代材料。
骨诱导 胶原; 珊瑚; 关键词: 骨形成蛋白;
α() 文章编号: 100823820 19990420234204 Q 512 A 中图分类号: 文献标识码:
Ecto ipc o steo in duc itonf o llow in g in tram uscular pimlan ta t iono f
, - 2a com po s ite of co lraco llagen a dn rhBM P
222, , ZHA N G Sen lin M EN G Zh ao yeSHOU Bo qu an e t a l
()210002, , , D ep a r tm en t of S tom a tology N a nj in g G en e ra l H osp ita l of PL A N a nj in g C h in a
( ) : 22 22, : A bstrac tO bj ec t ivesT o exam ine th e o steo induc t iv ity o f com b ina t io n o f recom b inan t h um an BM P rhBM P
. : 22, co llagen and co ra lT h e com b ina t io n o f rhBM P co llagen and co ra l d isc w a s im p lan ted in a back m u sM e th od s2
, 22 . c le po uch o f th e ra tand com b ina t io n o f co ra l and rhBM P o r co ra l and co llagen o n ly u sed a s th e co n t ro lO ne o r
, .fo u r w eek s af te r im p lan ta t io no steo induc t io n w a s exam ined by h isto lo g ica l eva lua t io n and h istom o rp hom e t ry
: 22 ƒƒR esu l tsA ll im p lan t s o f co ra lco llegan rhBM P show ed ca r t ilage o n th e su rface and in th e po re s o f co ra l a t o ne
, , w eek lam e lla r bo ne w ith bo ne m a r row a t fo u r w eek s and th e co ra l w a s ab so rbed p a r t ia llyand th e induced fo rm a2 t io n o f ca r t ilage and bo ne w a s rhBM P 22 do se2re la ted. A ll im p lan t s o f co ra lrhBM P 22 o r co ra lco llagen d id no t ƒƒshow any bo ne o r ca r t ilage fo rm a t io n. : 22, C on c lus ion sT h e com b ina t io n o f rhBM P co llagen and co ra l po sse sse s a
2 sup e r io r o steo induc t iv ity and w o u ld be exp ec ted to deve lop a s a ‘ se lfregene ra t ing bo ne im p lan t’ fo r c lin ica l u se in
.th e fu tu re
O steo induc t io n Key words: Co ra l; Co llagen; Bo ne m o rp ho gene t ic p ro te in;
g raf t in g p redom in an t ly u se s au to geno u s bo n e tak en 0 In troduc t ion . f rom a do no r site su ch a s th e an te r io r iliac c re st In th e f ie ld o f m ax illo fac ia l su rge ry it is n ece s2 , A ltho u gh h igh ly effec t iveau to lo go u s bo n e g raf t2
sa ry in m an y ca se s to f ill a bo n e defec t w ith bo n e in g is lim ited b y su ch issu e s a s do no r site m o rb id ity
, , an d p a in in c iden ce o f do no r site in fec t io n b loo d . , o r o th e r m a te r ia lA s cu r ren t ly p rac t icedbo n e
α 收稿日期: 1999201211
作者简介: 张森林, 男, 安徽庐江人, 医学硕士, 主治医师, 从事口腔颌面外科专业。
, lo ss du r in g g raf t h a rve stan d lim ited supp ly o f th en c lean ed o f o rgan ic p a r t s b y imm e r sio n in a 5% 1 , 4 .do no r site m a te r ia l fo r la rge sk e le ta l defec t 30. so lu t io n o f so d ium h ypo ch lo r ite fo r hA f te r th e , T h u sth e sea rch fo r a lte rn a t ive s to au to g raf t re2 so f t t issu e s h ad b een o x id ized, th e m a te r ia ls w e re .m a in s an im po r tan t top ic in m ed ica l re sea rch
r in sed in de io n ized w a te r fo r 30, h an d d r ied a t , In recen t yea r sco n side rab le re sea rch h a s fo 2
?,th en cu t in to d isk s w ith 8mm in d iam e te r 90cu sed o n im p ro v in g o steo regen e ra t io n th ro u gh th e 5 , 7 2. 55% an d mm in th ickCo ra l po ro sity w a s an d th e . , u se o f iso la ted BM P sT o da teiso fo rm s o f 120, 260.po re size ran ged f rom Λm in d iam e te r 8 1 9 . ,BM P f rom to h ave b een repo r ted O f th e se
1, 22Co ra l d isc s w e re imm e r sed in m g rhBM P 22 BM P h a s show n th e h igh e st o steo in du c t io n cap a2 2, 6, m ix ed w ith m g co llagen an d k ep t u n de r n ega2 9 . b ility an d is exp ec ted to b e app licab le c lin ica lly () 10, t ive p re ssu re T o r rin a vacu um p um p to a llow 22 R hBM P h a s b een p ro du ced b y recom b in an t DN A rep lacem en t o f th e a ir in th e po re s w ith so lu t io n o f 10 . tech no lo gy In exp e r im en ta l sy stem s p u re ec2 22. co llagen an d rhBM P T ho se d isc s w e re th en ,top ic o steo in du c t io n b y a sin g le BM P iso fo rm . , lyop h ilizedFo r th e co n t ro l g ro up co ra l d isc w ith , w h ich t ru ly ve r if ie s o steo in du c t io n h ave b een re2 6122 m g co llagen o r co ra l d isc w ith m g rhBM P o n ly11 . , po r ted T h e refo reth e n ex t issu e in BM P re2 . w a s p rep a red in th e sam e m an n e rS te r iliza t io n b e2 sea rch seem ed to b e m e tho d s o f m a in ta in in g th e o 2 .fo re im p lan ta t io n is ach ieved b y e th y len e o x ide r ig in a l fo rm o f th e BM P im p lan t af te r p u re o steo in2
(1. 2 S ix teen SD ra t s ave r2 S u rg e ry p roced u res .du c t io n ) age w e igh t, 40 g w e re an e sth e t ized b y in t ram u s2
2 a com po site o f recom b in an t h u In th is stu dy, ( )100 . 3. 5 ƒcu la r in jec t io n o f p en to b a rb ita l m g g
( ) m an BM P 22 rhBM P 22, c rea ted b y recom b in an t2 ( ) 10 Fo u r in c isio n s mm w e re m ade o n th e b ack o f
, ed DN A tech no lo gyco llagen an d co ra l d isc w a s , th e ra tan d m u sc le po u ch e s w e re m ade b y b lu n t
. im p lan ted in a b ack m u sc le po u ch o f th e ra tCo lla2 . : d issec t io nFo u r m a te r ia ls w e re im p lan tedco ra l gen w a s p rev io u sly show n to b e an effec t ive ca r r ie r w ith co llagen , co ra l w ith rhBM P 22, co ra l w ith co l2 11 . fo r ec top ic o steo in du c t io n b y BM P Co ra l h a s ( ) 22 1, lagen an d rhBM P m g an d co ra l w ith co lla2 b een u sed a s a f illin g m a te r ia l o f bo n e defec t an d is ()22 2. gen an d rhBM P m g T h e fa sc ia an d sk in w e re 12 . repo r ted to b e re so rb ed rap id ly in v iv o O n e o r .su tu red t igh t ly in each ca se
, th ree w eek s af te r im p lan ta t io n o steo in du c t io n w a s 1. 3 H is to log ica l s tudy a n d H is tom o rp h om e t ry
2ex am in ed b y h isto lo g ica l eva lu a t io n an d h isto m o r2 E igh t ra t s w e re sac r if iced each a t 1, 4 w eek s af te r p hom e t ry. . su rge ryT h e im p lan t s w e re h a rve sted w ith su r2
10% fo rm an in a t ro u n d in g so f t t issu e, f ix ed in 1 M a ter ia l an d m e thod s
n eu t ra l PH an d deca lc if ied b y th e fo rm ic ac id 1. 1 Im p la n t m a te r ia ls 22 R hBM P u sed in th e. 5m e tho dSec t io n s Λm th ick w e re sta in ed b y h em a2 exp e r im en t w a s m an u fac tu red b y recom b in an t ex 2 to x y lin an d eo sin an d o b se rved b y ligh t m i2 p re ssio n a t A cadem y o f M ilita ry M ed ica l Sc ien ce s c ro scop y.
() , . . B e ijin gC h in a in Eco liB io a ssay o f im p lan ta2 2ƒH E sta in ed h isto lo g ic sp ec im en s o f co ra lco l2 t io n o f m o u se th igh m u sc le show ed th a t th e ( )2 w e re qu an t ita t ive ly a sƒ22 1, 2 legan rhBM P m g
22 .rhBM P h ad a h igh ly o steo in du c t ive ac t iv ity se ssed fo r n ew bo n e o r ca r t ilage t issu e a t a stan2
( I ƒ 5 co llagen so lu t io n m gA te lop ep t ide typ e da rd m agn if ica t io n w ith th e Ze iss A x iop ho t M ic ro 2 , 3. 8. , m lpH B e ijin g G ran d B iom a te r ia l Com p an y( , , scop e Ze iss In st rum en t Com p an yN ew Yo rk
) , , , B e ijin g C h in a de r ived f rom f re sh po rc in e sk in ). N Y A f te r sa t isfac to ry op t ica l co n t ra st s w e re
22 .w a s u sed a s th e ca r r ie r fo r rhBM P in th is stu dy , ach ieved am o n g th e co n n ec t ive t issu ebo n e o r ca r2
, T h e gen e ra o f co ra l u sed w a s Po r ite sb e lo n g2 , t ilagean d ce llu lla r fea tu re s b y se lec t io n o f g ray
. , in g to th e M ad repo ra g ro upIt w a s o b ta in ed f rom leve l th a t w a s co n sisten t fo r a ll sec t io n sth e a rea
, , . ,San yaH a ilan P ro v in ceC h in aA f te r ga th e r in g o f bo n e o r ca r t ilage w ith in th e im p lan t site s w a s
.,m ea su red th e co ra l f ragm en t s w e re su n d r ied fo r a few day s
1. 4 S ta t is t ics H istom o rp hom e t r ic da ta w e re a ll
exp re ssed a s x ? s, an d sta t ist ica l an a ly se s w e re
2ca r r ied o u t u sin g stu den t’ s t te st fo r te st do sede2
22 p en den t effec t s o f rhBM P o n ca r t ilage an d bo n e
.t issu e fo rm a t io n w ith in im p lan t s
2 Re sults
2. 1 A ll im p lan t s o f H is to log ic eva lua t ion
co ra lco llegan rhBM P 22 show ed ca r t ilage co n sist2 ƒƒ in g o f m a tu re cho n d ro cy te s w ith a b a sop h ilic ex t ra2 ƒrhBM P- 2 im p lan t spec im en s show in g f i- Cora lF igure 3
ce llu la r m a t r ix o n th e su rface an d in th e po re s o f brova scular in va s ion in to cora l pore reg ion s a t
( ) , 1, f our week showever they d id n o t show an y car t i- co ra l a t o n e w eek F igu re lam e lla r bo n e w ith
()lage or bon e f orm a t ion. HE ×100 bo n e m a r row a t fo u r w eek s an d th e co ra l w a s ab 2
()2. ƒ so rb ed p a r t ia lly F igu re A ll im p lan t s o f co ra l
2. 2 H is tom o rp h om e t ry C a r t ilage o r bo n e t issu e 22 ƒrhBM P o r co ra lco llagen show ed f ib ro va scu la r
w ith in im p lan t s w a s qu an t if ied b y h istom o r2 in va sio n in to co ra l po re reg io n s w h e re m an y m u lt i2
()4. p hom e t ry F igu re S ta t ist ica l an a ly sis o f th e h is2 n u c lea ted g ian t ce lls w e re p re sen t an d d id no t show
22 tom o rp hom e t r ic da ta show ed th a t do se o f rhBM P an y bo n e o r ca r t ilage fo rm a t io n a t o n e o r fo u r
h ad sign if ican t effec t s o n th e a rea o f ca r t ilage o r ()w eek s F igu re 3.
( )22 2ƒƒbo n e t issu e an d co ra lco llagen rhBM P m g
( ) 22 1 ƒƒw a s sup e r io r to co ra lco llegan rhBM P m g a t
()< 0. 001.th e sam e t im e P
( ) - 2 1ƒƒ F igure 1 Cora lco llagen rhBM Pm g im p lan t spec i-
m en s show in g car t ilage f orm a t ion in pore s of
( )×100cora l a t on e week HE
F igure 4 Re sults of area of bon e or car t ilage w ith in the im -
p lan t s ite s
( )3 1222 1ƒƒm g and m g rep re sen t ing co ra lco llagenrhBM P m g
( ) 22 2ƒƒand co ra lco llagenrhBM P m gg ro up s re sp ec t ive ly
3 D iscuss ion
In c lin ica l p rac t ice th e re is no t a lw ay s o s2
teo gen ic t issu e w h ich w o u ld suppo r t v igo ro u s o s2
. teo co n du c t io n su r ro u n d in g th e bo n e defec tT o re2 ( ) ƒƒ- 2 1 Cora lco llagen rhBM Pm g im p lan t spec i-F igure 2 co n st ru c t th e bo n e defec t w itho u t leav in g a def i2
m en s show in g lam e llar bon e w ith bon e m arrow , c ien cy a l th e do no r siteo steo in du c t io n is exp ec ted
()×50f orm a t ion a t f our week s HE . , to p lay a ro leT h e refo reth e ab ility o f BM P to
p rom o te o steo in du c t io n sho u ld b e ex am in ed in a
p u re ec top ic in du c t io n sy stem w itho u t th e in f lu en ce co llagen in du ced th e imm a tu re m e sen ch ym a l ce lls
to d iffe ren t ia te in to cho n d ro cy te s lead in g to ca r t i2 o f o steo co n du c t io n an d w itho u t o th e r o steo gen ic
, . lage fo rm a t io n an d o steo gen e sis o ccu red in an en 2 ca r r ie r sO n ly u n de r an exp e r im en ta l sy stem ex am 2
11 in in g p u re o steo in du c t io n can th e ab ility o f BM P s . do cho n d ra l m an n e rT h e in du ced t rab ecu la r
.bo n e ten ded to face th e in n e r w a ll in m o st o f th e b e e st im a ted p rec ise ly
11 . po re s in w h ich n ew t rab ecu la r bo n e w a s fo u n dIt . F u jim u ra e t a lh ave p rev io u sly co n f irm ed
w a s tho u gh t th a t co ra l w a s a goo d scaffo ld fo r o s2 p u re ec top ic o steo in du c t io n af te r im p lan t in g
. , teo in du c t io nO ve r a llth is stu dy show ed th a t no t 22 rhBM P an d co llagen in to th e ra t ca lf m u sc le
o n ly a t th e o u te r su rface o f th e co ra l d isc b u t a lso . po u chB u t co llagen is a so lu t io n an d isn ’ t u sed a s
, in it s deep po re sp u re ec top ic o steo in du c t io n o c2 , a scaffo ld in a bo n e defec tan d it can ’ t b e app lica2
cu r red w itho u t o steo gen ic t issu e su r ro u n d in g th e . b le c lin ica lly in la rge bo n e defec t sK u sum o to e t
13 .im p lan t a rea . a lh ave de sc r ib ed t rab ecu la r bo n e fo rm a t io n af2
In co n t ro ls, co ra lƒrhBM P 22 o r co ra lƒco llagen 22, te r com b in a t io n o f rhBM P co llagen an d h yd ro x2
im p lan ted g ro up s d id no t show an y bo n e o r ca r t i2 yap a t ite w a s im p lan ted in a ca lf m u sc le po u ch o f
22 . lage fo rm a t io nIt w a s tho u gh t th a t rhBM P in . th e ra tCo n side r in g h yd ro x yap a t ite isn ’ t re so rb ed
22 ƒ2co ra lrhBM P im p lan ted g ro up s d idn ’ t o b ta in op 2 , in v ivo o ve r th e lo n gte rm th e com b in a t io n m ay
t im a l o steo in du c t ive ty to d iffu se th ro u gho u t th e d istu rb bo n e rem o de lin g in th e im p lan ted a rea an d
ta rge t m e sen ch ym a l ce lls w h en co llagen ca r r ie r w a s .cau se d iff icu lty in th e fu n c t io n in g o f no rm a l bo n e
()22 1.ab sen t an d am o u n t o f rhBM P w a s sm a ll m g , D u r in g th e la st decade yea rco ra l h a s b een
su cce ssfu lly u sed a s a bo n e su b st itu te in m o st su r2 22, T h en a com b in a t io n o f rhBM P co llagen an d
14, 15 . co ra l sho u ld b e im p lan ted in so f t t issu e an d sho u ld g ica l f ie ld sP re sen t in g ex ce llen t b io com p a t i2
, lead to o steo in du c t io n an d it can b e re so rb ed an d , b ility an d o steo co n du c t ive p rop e r t ie sit is w ide ly
. rep laced g radu a lly b y bo n eIt w o u ld b e exp ec ted , .ava ilab lech eap an d ea sily p rep a red an d sh ap ed
2to deve lop a s a ‘ se lfregen e ra t in g bo n e im p lan t’ fo r . It s po ro u s st ru c tu re is sim ila r to th a t o f bo n e
, .W h en im p lan ted in to bo n e t issu eit is p ro g re ssive2 c lin ica l u se in th e fu tu re
, , ly re so rb ed b y o steo c la st sw h ilea t th e sam e Ref eren ce s: , , , t im eo steo b la st su sin g th e f reed ca lc ium io n s
. 1 , . p ro du ce n ew bo n eT h e deg rada t io n ra te o f co ra l in C a r lso n ER M a rx R EM and ibu la r reco n st ruc t io n u sing can2
6 [ . ,ce llo u s ce llu la r bo ne g raf t s J J O ra l M ax illo fac Su rg 50% 6 100% 3 . bo n e is a t w eek s an d a t m o n th s1996, 54: 889. , Co n side r in g co ra l h a sn ’ t o steo in du c t iv ityex cep t . [ . 2 M a rx R EM and ibu la r reco n st ruc t io n J J O ra l M ax illo fac
, fo r ve ry sm a ll defec t sth is ra te o f deg rada t io n is , 1993, 51: 466.Su rg
, . 3 T id st rom KD Ke lle r E ER eco n st ruc t io n o f m and ibu la r d is2 too rap id to a ssu re com p le te bo n e h ea lin g b y o steo 2 [ . co n t inu ity w ith au to geno u s lliac bo ne g raf t J J O ra l M ax2 14 .co n du c t io n , 1990, 48: 336.illo fac Su rg
T h e p re sen t stu dy dem o n st ra ted fo r th e f ir st . 4 W e lls M DM and ibu la r reco n st ruc t io n u sing va scu la r ized
[. , 1996, 54: 883.bo ne g raf t s J J O ra l M ax illo fac Su rg , 22, t im e th a t a sin g le recom b in an t BM P rhBM P B e ssho K , Iizuk a T. A c t iv ity and so lub ility o f bo ne m o rp ho 2 5 , reco n st itu ted w ith co llagen an d co ra lin du ced ca r2 [. gene t ic p ro te in de r ived f rom po rc ine bo ne m a t r ix J B r J O 2 , t ilage an d bo n e fo rm a t io n in ec top ic site san d th e , 1994, 32: 86.ra l M ax illo fac Su rg
, , . B e ssho K T agaw a T M u ra ta M Com p a r iso n o f bo ne m a2 6 2en do cho n d ra l bo n e w a s in a do sedep en den t m an2 2t r ix de r ived bo ne m o rp ho gene t ic p ro te in s f rom va r io u s an i2 n e r. It w a s tho u gh t th a t rhB P 22 an d co llagen so lu 2 [ . , 1992, 50: 496.m a lsJ J O ra l M ax illo fac Su rg , t io n in w h ich th e co ra l d isc w a s so ak ed to f ill a ll , , . 222 M ik i T H a rada K Im a i Y et a lE ffec t o f f reezed r ied po lyl7
lac t ic ac id d isc s m ixed w ith bo ne m o rp ho gene t ic p ro te in o n th e , po re saffec ted imm a tu re m e sen ch ym a l ce lls w h ich [. , 1994,h ea ling o f ra t sk u ll defec t s J J O ra lM ax illo fac Su rg in f ilt ra ted f rom th e su r ro u n d in g m u sc le in to th e 52: 387. . 22 deep po re s o f th e co ra l d iscT h en rhBM P w ith
第 12 卷 第 4 期 V o l. 12 N o. 4 医 学 研 究 生 学 报 1999 年 11 月 N o v. 1999 Jo u rn a l o f M ed ica l Po s tg radu a te
保存人羊膜用于兔眼表面重建的印痕细胞学研究
薛春燕, 黄振平
()南京军区南京总医院眼科, 南京 210002
摘要: 目的: 观察羊膜移植术在角膜缘缺陷兔眼表层重建中的作用, 并探讨印痕细胞学检查法随访的价值。 方 法: 建立兔全角膜缘缺陷的动物模型, 实验眼早期应用保存的人羊膜移植于受损区域, 对照眼常规保守治疗, 观察 其角膜新生血管及上皮层愈合情况。 上皮层愈合后, 采用印痕细胞学检查, 定期对角膜区上皮进行表层细胞学检
查。 结果: 对照眼角膜上皮层愈合较慢, 新生血管粗大丰富, 上皮细胞层不稳定, 含有杯状细胞。羊膜移植的眼表面上皮层愈合快, 新生血管细小, 上皮层光滑、稳定, 周边部在上皮愈合 1 个月后仍含有丰富的杯状细胞。 结论: 羊膜移植能促进上皮细胞移行, 抑制上皮细胞凋亡, 获得稳定的眼表层。羊膜移植后, 上皮仍表现为结膜型上皮。印 痕细胞学检查简便、无创, 可满意地用于随访眼球表面情况。
关键词: 印痕细胞学; 羊膜移植; 眼表面重建
() 中图分类号: 446. 5 文献标识码: 文章编号: 100823820 19990420238205 R A
以下实验。 0 引言
1 材料和方法 1 自从 等报道了甘油保存的人羊膜能够成 K im
功地重建严重酸烧伤的兔眼, 部分获得透明的角膜 111 角膜缘缺陷动物模型的建立 ?新西兰白兔
( ) 以来, 人们开始重视羊膜在眼科的应用。为了研究羊 10 只 南京总医院动物实验中心提供, 体重 2. 0,
膜移植对角膜缘缺陷兔眼的治疗作用, 我们进行了 2. 5 , 雌雄兼有。 右眼为正常观察眼, 左眼为实验k g
收稿日期: 1999204229
( ) 1971- , 作者简介: 薛春燕 女, 江苏常州人, 医学硕士, 医师, 从事眼科专业角膜病的基础及临床研究。
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