Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.
Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 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-β3 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-β3 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.
Department of Molecular Science & Technology, Ajou University, Suwon, Republic of Korea.
Soon Sim
SS
Yang
Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea.
Long Hao
LH
Jin
Department of Biomedical Engineering, Pukyong National University, Busan, Republic of Korea.
Sang-Hyug
SH
Park
Department of Molecular Science & Technology, Ajou University, Suwon, Republic of Korea.
Moon Suk
MS
Kim
Cell Therapy Center, Ajou University Medical Center, Suwon, Republic of Korea.
Young Jick
YJ
Kim
Division of Biomedical and Bioengineering Sciences, Inha University College of Medicine, Incheon, Republic of Korea.
Byung Hyune
BH
Choi
Lee Chun Tek Orthopedic Specialty Hospital, Suwon, Republic of Korea.
Chun Tek
CT
Lee
Department of Physiology, College of Medicine, Inha University, Incheon, Republic of Korea.
So Ra
SR
Park
Department of Molecular Science & Technology, Ajou University, Suwon, Republic of Korea.|Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea.|Cell Therapy Center, Ajou University Medical Center, Suwon, Republic of Korea.
Byoung-Hyun
BH
Min
D000818:Animals; D001681:Biological Assay; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D002942:Circular Dichroism; D005109:Extracellular Matrix / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3