Biodegradable water-based polyurethane scaffolds with a sequential release function for cell-free cartilage tissue engineering
Abstract
Three-dimensional (3D) printing technology has rapidly developed as a promising technology for manufacturing tissue engineering scaffolds. Cells used in tissue engineering are subjected to the quality management and risk of contamination, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this study, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature (-40 °C) to fabricate tissue engineering scaffolds with sequential drug release function. The scaffolds containing 200 ng/ml SDF-1 and 22 wt% Y27632-encapsulated microspheres (55 µg/ml Y27632 in microspheres) (abbreviated PU/SDF-1/MS_Y scaffolds) had the optimal performance. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro and reach the effective concentration (∼100 ng/ml and 3.38 µg/ml, respectively) after the appropriate time (24 h and 62 h, respectively). Human mesenchymal stem cells (hMSCs) seeded in the scaffolds showed significant GAG deposition in 7 days. Besides, the gradual release of SDF-1 from the PU/SDF-1/MS_Y scaffolds could induce the migration of hMSCs. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. The 3D printed scaffolds with sequential releases of SDF-1 and Y27632 may have potential in cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: The clinical success of tissue engineering depends highly on the quality of externally supplied cells, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this manuscript, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature to fabricate tissue engineering scaffolds with sequential drug release function. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro. SDF-1 was released earlier from the scaffolds to promote cell migration. The drug Y27632 was released later from the microspheres into the matrix of the scaffolds to induce the chondrogenic differentiation of the attracted cells. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. We hypothesized that the cell-free scaffolds may improve the clinical applicability and convenience without the use of exogenous cells or growth factor.
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The LTD printing process is carried out at low temperatures, which preserves the bioactivity of temperature-sensitive bioactive agents such as growth factors and extracellular matrix proteins.
“Unlike the FDM and SLS methods, the LTD printing process is carried out at low temperatures, which preserves the bioactivity of temperature-sensitive bioactive agents, such as growth factors and extracellular matrix proteins [109, 110].”
From Application of PLCL as a biodegradable polymer in biomedical engineering (2026) · cites this paper as [109]
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- Authors
- Wen, Y.-T., Dai, N.-T., & Hsu, S.-H.
- Affiliations
- National Taiwan University (TW)
- National Defense Medical Center (TW)
- Corresponding author
- Hsu, Shan-hui
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 88
- Pages
- 301-313
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2918077371
- Cited by
- 91
- References
- 39
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 14 · 2023: 15 · 2022: 18 · 2021: 17 · 2020: 10 · 2019: 1
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology, Taiwan (106-2221-E-002-079-MY2, 106-2622-E-002-007-CC1)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- sequential drug release, Y-27632, human mesenchymal stem cells, cartilage regeneration, articular cartilage defects, low-temperature printing, cell migration
- MeSH terms
- Animals, Biocompatible Materials, Cartilage, Cell Movement, Humans, Male, Microspheres, Polyurethanes, Rabbits, Regeneration, Water, Chemokines, Chondrogenesis, Tissue Engineering, Cell Proliferation, Chemokine CXCL12, Tissue Scaffolds, Mesenchymal Stem Cells, Drug Liberation
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