A novel injectable approach for cartilage formation in vivo using PLG microspheres

被引:44
作者
Mercier, NR
Costantino, HR
Tracy, MA
Bonassar, LJ
机构
[1] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA
[2] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA USA
[3] Alkermes Inc, Cambridge, MA USA
关键词
cartilage; tissue engineering; PLG; proteoglycan; microsphere; cell delivery;
D O I
10.1023/B:ABME.0000017547.84146.fd
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
This study documents the use of biodegradable poly(lactide-co-glycolide) (PLG) microspheres as a novel, injectable scaffold for cartilage tissue engineering. Chondrocytes were delivered via injection to the subcutaneous space of athymic mice in the presence and absence of PLG microspheres. Tissue fort-nation was evaluated up to 8 weeks post-injection. Progressive cartilage formation was observed in samples containing microspheres. The presence of microspheres increased the quantity of tissue formed, the amount of glycosaminoglycan that accumulated, and the uniformity of type II collagen deposition. Microsphere composition influenced the growth of the tissue engineered cartilage. Higher molecular weight PLG resulted in a larger mass of cartilage formed and a higher content of proteoglycans. Microspheres comprised PLG with methyl ester end groups yielded increased tissue mass and matrix accumulation, but did not display homogenous matrix deposition. The microencapsulation of Mg(OH)(2) had negative effects on tissue mass and matrix accumulation. Matrix accumulation, cell number, and tissue mass were unchanged by microsphere size, but larger microspheres increased the frequency of central necrosis in implants. The data herein reflect the promising utility of an injectable PLG-chondrocyte system for tissue engineering applications.
引用
收藏
页码:418 / 429
页数:12
相关论文
共 25 条
[1]  
Chang SCN, 2001, J BIOMED MATER RES, V55, P503, DOI 10.1002/1097-4636(20010615)55:4<503::AID-JBM1043>3.0.CO
[2]  
2-S
[3]   THE EFFECT OF PH ON THE INVITRO DEGRADATION OF POLY(GLYCOLIDE LACTIDE) CO-POLYMER ABSORBABLE SUTURES [J].
CHU, CC .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1982, 16 (02) :117-124
[4]   Development of poly-(D,L-lactide-coglycolide) microsphere formulations containing recombinant human vascular endothelial growth factor to promote local angiogenesis [J].
Cleland, JL ;
Duenas, ET ;
Park, A ;
Daugherty, A ;
Kahn, J ;
Kowalski, J ;
Cuthbertson, A .
JOURNAL OF CONTROLLED RELEASE, 2001, 72 (1-3) :13-24
[5]   Controlled-release of IGF-I and TGF-β1 in a photopolymerizing hydrogel for cartilage tissue engineering [J].
Elisseeff, J ;
McIntosh, W ;
Fu, K ;
Blunk, T ;
Langer, R .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2001, 19 (06) :1098-1104
[6]   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
[7]   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
[8]   Human chondrocytes proliferate and produce matrix components in microcarrier suspension culture [J].
Frondoza, C ;
Sohrabi, A ;
Hungerford, D .
BIOMATERIALS, 1996, 17 (09) :879-888
[9]   IGF-I and mechanical environment interact to modulate engineered cartilage development [J].
Gooch, KJ ;
Blunk, T ;
Courter, DL ;
Sieminski, AL ;
Bursac, PM ;
Vunjak-Novakovic, G ;
Freed, LE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 286 (05) :909-915
[10]   MECHANICAL AND PHYSICOCHEMICAL DETERMINANTS OF THE CHONDROCYTE BIOSYNTHETIC RESPONSE [J].
GRAY, ML ;
PIZZANELLI, AM ;
GRODZINSKY, AJ ;
LEE, RC .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1988, 6 (06) :777-792