Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair

被引:809
作者
Kisiday, J
Jin, M
Kurz, B
Hung, H
Semino, C
Zhang, S
Grodzinsky, AJ
机构
[1] MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA
[2] MIT, Biol Engn Div, Cambridge, MA 02139 USA
[3] MIT, Dept Mech, Cambridge, MA 02139 USA
[4] MIT, Dept Elect Engn, Cambridge, MA 02139 USA
关键词
three-dimensional cell culture; biological scaffold; regenerative medicine;
D O I
10.1073/pnas.142309999
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.
引用
收藏
页码:9996 / 10001
页数:6
相关论文
共 46 条
[1]   DEDIFFERENTIATED CHONDROCYTES REEXPRESS THE DIFFERENTIATED COLLAGEN PHENOTYPE WHEN CULTURED IN AGAROSE GELS [J].
BENYA, PD ;
SHAFFER, JD .
CELL, 1982, 30 (01) :215-224
[2]   TREATMENT OF DEEP CARTILAGE DEFECTS IN THE KNEE WITH AUTOLOGOUS CHONDROCYTE TRANSPLANTATION [J].
BRITTBERG, M ;
LINDAHL, A ;
NILSSON, A ;
OHLSSON, C ;
ISAKSSON, O ;
PETERSON, L .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (14) :889-895
[3]   INDUCTION AND PREVENTION OF CHONDROCYTE HYPERTROPHY IN CULTURE [J].
BRUCKNER, P ;
HORLER, I ;
MENDLER, M ;
HOUZE, Y ;
WINTERHALTER, KH ;
EICHBENDER, SG ;
SPYCHER, MA .
JOURNAL OF CELL BIOLOGY, 1989, 109 (05) :2537-2545
[4]   The effects of scaffold thickness on tissue engineered cartilage in photocrosslinked poly(ethylene oxide) hydrogels [J].
Bryant, SJ ;
Anseth, KS .
BIOMATERIALS, 2001, 22 (06) :619-626
[5]  
BUSCHMANN MD, 1995, J CELL SCI, V108, P1497
[6]   CHONDROCYTES IN AGAROSE CULTURE SYNTHESIZE A MECHANICALLY FUNCTIONAL EXTRACELLULAR-MATRIX [J].
BUSCHMANN, MD ;
GLUZBAND, YA ;
GRODZINSKY, AJ ;
KIMURA, JH ;
HUNZIKER, EB .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1992, 10 (06) :745-758
[7]   Self-assembly of a β-sheet protein governed by relief of electrostatic repulsion relative to van der Waals attraction [J].
Caplan, MR ;
Moore, PN ;
Zhang, SG ;
Kamm, RD ;
Lauffenburger, DA .
BIOMACROMOLECULES, 2000, 1 (04) :627-631
[8]   Depth- and strain-dependent mechanical and electromechanical properties of full-thickness bovine articular cartilage in confined compression [J].
Chen, AC ;
Bae, WC ;
Schinagl, RM ;
Sah, RL .
JOURNAL OF BIOMECHANICS, 2001, 34 (01) :1-12
[9]   Redifferentiation of dedifferentiated bovine articular chondrocytes in alginate culture under low oxygen tension [J].
Domm, C ;
Schünke, M ;
Christesen, K ;
Kurz, B .
OSTEOARTHRITIS AND CARTILAGE, 2002, 10 (01) :13-22
[10]   SWELLING OF ARTICULAR-CARTILAGE AND OTHER CONNECTIVE TISSUES - ELECTROMECHANOCHEMICAL FORCES [J].
EISENBERG, SR ;
GRODZINSKY, AJ .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1985, 3 (02) :148-159