In situ chondrogenic differentiation of human adipose tissue-derived stem cells in a TGF-β1 loaded fibrin-poly(lactide-caprolactone) nanoparticulate complex
- In situ chondrogenic differentiation of human adipose tissue-derived stem cells in a TGF-β1 loaded fibrin-poly(lactide-caprolactone) nanoparticulate complex
- 정영미; 정용일; 김상희; 태기융; 김영하; 이종원; 김상헌; 김수현
- Human adipose tissue-derived stem cells; Chondrogenic differentiation; TGF-β1; Poly(L-lactide-co-ε-caprolactone) scaffold
- Issue Date
- VOL 30, NO 27, 4657-4664
- When conducting cartilage tissue engineering with stem cells, it is well known that chemical and
physical stimulations are very important for the induction and maintenance of chondrogenesis. In this
study, we induced chondrogenic differentiation of human adipose tissue-derived stem cells (hASCs)
in situ by effective stimulation via the continuous controlled release of TGF-b1 from a heparin-functionalized
nanoparticle–fibrin–poly(lactide-co-caprolactone) (PLCL) complex. PLCL scaffolds were fabricated
with 85% porosity and 300–500 mm pore size by a gel-pressing method. Heparin-functionalized
nanoparticles were prepared by a solvent-diffusion method, composed of poly(lactide-co-glycolide)
(PLGA), Pluronic F-127, and heparin, and then TGF-b1 was loaded to the nanoparticles. A mixture of
hASCs, fibrin gels and TGF-b1 loaded nanoparticles was then seeded onto PLCL scaffolds and cultured in
vitro, after which they were subcutaneously implanted into nude mice for up to five weeks. The results of
in vitro and in vivo studies revealed that chondrogenic differentiation of the hASCs on the complex was
induced and sustained by continuous stimulation by TGF-b1 from the heparin-functionalized nanoparticles.
In addition, there was no significant difference between the predifferentiation condition prior
to incubation in chondrogenic medium and the proliferation condition, which suggests that in situ
chondrogenic differentiation of hASCs was induced by the TGF-b1 loaded nanoparticles. Consequently,
the hybridization of fibrin and PLCL scaffolds for three-dimensional spatial organization of cells and the
effective delivery of TGF-b1 using heparin-functionalized nanoparticles can induce hASCs to differentiate
to a chondrogenic lineage and maintain their phenotypes.
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