Open AccessExtracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair
Author(s) -
Soon Sim Yang,
Long Hao Jin,
Sang-Hyug Park,
Moon Suk Kim,
Young Jick Kim,
Byung Hyune Choi,
Chun Tek Lee,
Sora Park,
ByoungHyun Min
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0156292
Subject(s) - chondrogenesis , cartilage , extracellular matrix , mesenchymal stem cell , ex vivo , microbiology and biotechnology , chemistry , in vivo , drug delivery , in vitro , biology , anatomy , biochemistry , organic chemistry
Recombinant human transforming growth factor beta-3 (rhTGF-β 3 ) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β 3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β 3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β 3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro . The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β 3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.