In situ chondrogenic differentiation of human adipose tissue-derived stem cells in a TGF-β1 loaded fibrin–poly(lactide-caprolactone) nanoparticulate complex
Abstract
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-beta1 from a heparin-functionalized nanoparticle-fibrin-poly(lactide-co-caprolactone) (PLCL) complex. PLCL scaffolds were fabricated with 85% porosity and 300-500 microm 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-beta1 was loaded to the nanoparticles. A mixture of hASCs, fibrin gels and TGF-beta1 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-beta1 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-beta1 loaded nanoparticles. Consequently, the hybridization of fibrin and PLCL scaffolds for three-dimensional spatial organization of cells and the effective delivery of TGF-beta1 using heparin-functionalized nanoparticles can induce hASCs to differentiate to a chondrogenic lineage and maintain their phenotypes.
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Further optimization of scaffold's rigidity-flexibility balance is required to withstand complex biomechanical stresses within joints.
“Nevertheless, further optimization of the scaffold’s rigidity-flexibility balance is required to withstand the complex biomechanical stresses within joints [197].”
From Application of PLCL as a biodegradable polymer in biomedical engineering (2026) · cites this paper as [197]
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- Authors
- Jung, Y., Chung, Y.-I., Kim, S. H., Tae, G., Kim, Y. H., Rhie, J. W., Kim, S.-H., & Kim, S. H.
- Affiliations
- Korea Institute of Science and Technology (KR)
- Gwangju Institute of Science and Technology (KR)
- Catholic University of Korea (KR)
- Corresponding author
- Kim, Soo Hyun
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 30
- Issue
- 27
- Pages
- 4657-4664
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2160354233
- Cited by
- 77
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 8
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- chondrogenic differentiation, adipose-derived stem cells, TGF-β1, controlled drug release, fibrin, cartilage tissue engineering, PLGA, Pluronic F127, in situ differentiation
- MeSH terms
- Adipose Tissue, Animals, Cell Differentiation, Female, Fibrin, Gene Expression Regulation, Glycosaminoglycans, Humans, Mice, Nude, Middle Aged, Polyesters, RNA, Messenger, Stem Cells, Reverse Transcriptase Polymerase Chain Reaction, Chondrogenesis, Mice, Nanoparticles, Transforming Growth Factor beta1
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