Delivery of TGF-β1 and chondrocytes via injectable, biodegradable hydrogels for cartilage tissue engineering applications

被引:221
作者
Park, H
Temenoff, JS
Holland, TA
Tabata, Y
Mikos, AG
机构
[1] Rice Univ, Dept Bioengn, Houston, TX 77251 USA
[2] Kyoto Univ, Inst Frontier Med Sci, Dept Biomat Field Tissue Engn, Sakyo Ku, Kyoto 6068507, Japan
基金
美国国家卫生研究院;
关键词
cartilage tissue engineering; cell encapsulation; drug delivery; injectable hydrogel; transforming growth factor-beta 1;
D O I
10.1016/j.biomaterials.2005.05.083
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
In this work, novel hydrogel composites, based on the biodegradable polymer, oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (MPs) were utilized as injectable cell and growth factor carriers for cartilage tissue engineering applications. Specifically, bovine chondrocytes were embedded in composite hydrogels co-encapsulating gelatin MPs loaded with transforming growth factor-beta 1 (TGF-beta 1). Hydrogels with embedded cells co-encapsulating unloaded MPs and those with no MPs served as controls in order to assess the effects of MPs and TGF-beta 1 on chondrocyte function. Samples were cultured up to 28 days in vitro. By 14 days, cell attachment to embedded gelatin MPs within the constructs was observed via light microscopy. Bioassay results showed that, over the 21 day period, there was a statistically significant increase in cellular proliferation for samples containing gelatin MPs, but no increase was exhibited in samples without MPs over the culture period. The release of TGF-beta 1 further increased cell construct cellularity. Over the same time period, glycosaminoglycan content per cell remained constant for all formulations, suggesting that the dramatic increase in cell number for samples with TGF-beta 1-loaded MPs was accompanied by maintenance of the cell phenotype. Overall, these data indicate the potential of OPF hydrogel composites containing embedded chondrocytes and TGF-beta 1-loaded gelatin MPs as a novel strategy for cartilage tissue engineering. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7095 / 7103
页数:9
相关论文
共 24 条
[1]  
ADOLPHE M, 1992, BIOL REGULATION CHRO
[2]   Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels [J].
Bryant, SJ ;
Anseth, KS .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 2002, 59 (01) :63-72
[3]   IMPROVED QUANTITATION AND DISCRIMINATION OF SULFATED GLYCOSAMINOGLYCANS BY USE OF DIMETHYLMETHYLENE BLUE [J].
FARNDALE, RW ;
BUTTLE, DJ ;
BARRETT, AJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 883 (02) :173-177
[4]   Thermoreversible hydrogel scaffolds for articular cartilage engineering [J].
Fisher, JP ;
Jo, S ;
Mikos, AG ;
Reddi, AH .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2004, 71A (02) :268-274
[5]   Transforming growth factor-β1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment [J].
Holland, TA ;
Tessmar, JKV ;
Tabata, Y ;
Mikos, AG .
JOURNAL OF CONTROLLED RELEASE, 2004, 94 (01) :101-114
[6]   In vitro release of transforming growth factor-β1 from gelatin microparticles encapsulated in biodegradable, injectable oligo(poly(ethylene glycol) fumarate) hydrogels [J].
Holland, TA ;
Tabata, Y ;
Mikos, AG .
JOURNAL OF CONTROLLED RELEASE, 2003, 91 (03) :299-313
[7]   Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering [J].
Holland, TA ;
Tabata, Y ;
Mikos, AG .
JOURNAL OF CONTROLLED RELEASE, 2005, 101 (1-3) :111-125
[8]   Advances in drug delivery for articular cartilage [J].
Holland, TA ;
Mikos, AG .
JOURNAL OF CONTROLLED RELEASE, 2003, 86 (01) :1-14
[9]   Low-density cultures of bovine chondrocytes: effects of scaffold material and culture system [J].
Hu, JC ;
Athanasiou, KA .
BIOMATERIALS, 2005, 26 (14) :2001-2012
[10]  
Hunziker EB, 2001, CLIN ORTHOP RELAT R, pS182