Mechanical properties and remodeling of hybrid cardiac constructs made from heart cells, fibrin, and biodegradable, elastomeric knitted fabric

被引:94
作者
Boublik, J
Park, H
Radisic, M
Tognana, E
Chen, F
Pei, M
Vunjak-Novakovic, G
Freed, LE
机构
[1] MIT, Div Hlth Sci & Technol, Space Res Ctr, Cambridge, MA 02139 USA
[2] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[3] Rhode Isl Hosp, Providence, RI 02903 USA
来源
TISSUE ENGINEERING | 2005年 / 11卷 / 7-8期
关键词
D O I
10.1089/ten.2005.11.1122
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Hybrid cardiac constructs with mechanical properties suitable for in vitro loading studies and in vivo implantation were constructed from neonatal rat heart cells, fibrin ( Fn), and biodegradable knitted fabric ( Knit). Initial ( 2- h) constructs were compared with native heart tissue, studied in vitro with respect to mechanical function ( stiffness, ultimate tensile strength [ UTS], failure strain epsilon(f), strain energy density E) and compositional remodeling ( collagen, DNA), and implanted in vivo. For 2- h constructs, stiffness was determined mainly by the Fn and was half as high as that of native heart, whereas UTS, epsilon(f), and E were determined by the Knit and were, respectively, 8-, 7-, and 30- fold higher than native heart. Over 1 week of static in vitro culture, cell- mediated, serum- dependent remodeling was demonstrated by a 5- fold increase in construct collagen content and maintenance of stiffness not observed in cell- free constructs. Cyclic stretch further increased construct collagen content in a manner dependent on loading regimen. The presence of cardiac cells in cultured constructs was demonstrated by immunohistochemistry ( troponin I) and Western blot ( connexin 43). However, in vitro culture reduced Knit mechanical properties, decreasing UTS, epsilon(f), and E of both constructs and cell- free constructs and motivating in vivo study of the 2- h constructs. Constructs implanted subcutaneously in nude rats for 3 weeks exhibited the continued presence of cardiomyocytes and blood vessel ingrowth by immunostaining for troponin I, connexin 43, and CD- 31. Together, the data showed that hybrid cardiac constructs initially exhibited supraphysiologic UTS, epsilon(f), and E, and remodeled in response to serum and stretch in vitro and in an ectopic in vivo model.
引用
收藏
页码:1122 / 1132
页数:11
相关论文
共 40 条
[1]   Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts [J].
Akhyari, P ;
Fedak, PWM ;
Weisel, RD ;
Lee, TYJ ;
Verma, S ;
Mickle, DAG ;
Li, RK .
CIRCULATION, 2002, 106 (13) :I137-I142
[2]   Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies [J].
Bursac, N ;
Papadaki, M ;
Cohen, RJ ;
Schoen, FJ ;
Eisenberg, SR ;
Carrier, R ;
Vunjak-Novakovic, G ;
Freed, LE .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1999, 277 (02) :H433-H444
[3]   Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme [J].
Camenisch, TD ;
Spicer, AP ;
Brehm-Gibson, T ;
Biesterfeldt, J ;
Augustine, ML ;
Calabro, A ;
Kubalak, S ;
Klewer, SE ;
McDonald, JA .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (03) :349-360
[4]   Semisynthetic resorbable materials from hyaluronan esterification [J].
Campoccia, D ;
Doherty, P ;
Radice, M ;
Brun, P ;
Abatangelo, G ;
Williams, DF .
BIOMATERIALS, 1998, 19 (23) :2101-2127
[5]  
Carrier RL, 1999, BIOTECHNOL BIOENG, V64, P580, DOI 10.1002/(SICI)1097-0290(19990905)64:5<580::AID-BIT8>3.0.CO
[6]  
2-X
[7]   CULTURE OF CARDIAC-MUSCLE-CELLS IN SERUM-FREE MEDIA [J].
CLAYCOMB, WC .
EXPERIMENTAL CELL RESEARCH, 1981, 131 (01) :231-236
[8]   Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system [J].
Eschenhagen, T ;
Fink, C ;
Remmers, U ;
Scholz, H ;
Wattchow, J ;
Weil, J ;
Zimmerman, W ;
Dohmen, HH ;
Schafer, H ;
Bishopric, N ;
Wakatsuki, T ;
Elson, EL .
FASEB JOURNAL, 1997, 11 (08) :683-694
[9]   Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement [J].
Fink, C ;
Ergün, S ;
Kralisch, D ;
Remmers, U ;
Weil, J ;
Eschenhagen, T .
FASEB JOURNAL, 2000, 14 (05) :669-679
[10]   NEOCARTILAGE FORMATION INVITRO AND INVIVO USING CELLS CULTURED ON SYNTHETIC BIODEGRADABLE POLYMERS [J].
FREED, LE ;
MARQUIS, JC ;
NOHRIA, A ;
EMMANUAL, J ;
MIKOS, AG ;
LANGER, R .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1993, 27 (01) :11-23