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Review Open Access

Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review)

  • Authors:
    • Gunasekara Wijesinghege Nimanthi Kaushalya
    • Sanath Rajapakse
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Biology and Biotechnology, Faculty of Science, University of Peradeniya, Peradeniya 20400, Sri Lanka
    Copyright: © Kaushalya et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 33
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    Published online on: April 24, 2026
       https://doi.org/10.3892/mi.2026.317
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Abstract

Cartilage is a strong, yet flexible, type of connective tissue found in various parts of the body. Cartilage that covers the ends of bones in joints, referred to as articular cartilage, is frequently damaged during injuries and osteoarthritis (OA). Lack of blood vessels and nerves in the cartilage limits its self‑renewal capacity, rendering cartilage regeneration a critical challenge. Three‑dimensional (3D) bioprinting provides a promising approach for cartilage regeneration by depositing bioink layer by layer to create a 3D structure of more complex tissues such as cartilage, with clinically relevant sizes and mimicking the native shape and natural microenvironment. The present review discusses the potential of bioprinting materials to direct the fate of induced pluripotent stem cells (iPSCs) towards chondrocytes, while simultaneously enhancing lubrication. This will be achieved by incorporating iPSCs, natural polymers, synthetic polymers and lubricants such as lubricin, growth factors and signaling molecules that are involved in chondrogenesis. By optimizing bioink formulation and other parameters in bioprinters, the production of tissues in a precisely controlled manner is ensured, and limitations in current treatments for degenerative diseases such as OA can be avoided. Researchers have developed various complex and functional tissues and organs using bioprinting with successful animal trials, and are in the process of developing patient‑specific iPSCs to generate personalized cartilage grafts having high and prolonged regenerative ability with further enhanced lubrication. The present review aimed to provide hope for patients suffering from cartilage degeneration by demonstrating the potential of 3D bioprinting for effective cartilage regeneration.
View Figures

Figure 1

Anatomy of the leg: This image
illustrates the long bones of the leg, highlighting the smooth
articular cartilage covering the joint surfaces and the presence of
red bone marrow within the spongy bone. The information presented
in the image was obtained from previous studies (6-10).

Figure 2

Chondrogenesis: The phases of
chondrogenesis are illustrated, beginning with MSCs and ending with
the development of hypertrophic chondrocytes. The information
presented in the image was obtained from previous studies (4,31). MSCs,
mesenchymal stem cells; BM, bone marrow.

Figure 3

Diagrammatic illustration of
cartilage regeneration using iPSCs. By introducing particular
transcription factors, somatic cells can be transformed into iPSCs.
These iPSCs have the potential to develop into cartilage-producing
chondrocytes. The procedure for creating cartilage tissue from
cells iPSCs is shown in this schematic. Certain transcription
factors, including OCT4, SOX2, KLF4 and Myc, are introduced into
the somatic cells of an individual (fibroblasts, for example) to
reprogram them into iPSCs. These iPSCs can differentiate into a
variety of cell types, including chondrocytes, which are the cells
that form cartilage. A series of signaling events and the
activation of important transcription factors coordinate the
differentiation process. An early transcription factor called Runx2
is essential for starting chondrogenesis. Subsequently, genes
involved in the synthesis of cartilage matrix, including collagen
type II and aggrecan, are expressed in response to SOX9, another
essential transcription factor. Following a maturation process, the
differentiated chondrocytes go from proliferative to
pre-hypertrophic and ultimately hypertrophic. The information
presented in the image was obtained from previous studies (31,32,35,57-65).
iPSCs, induced pluripotent stem cells.

Figure 4

Schematic illustration of the complex
interplay of signaling pathways for chondrocyte differentiation.
The complex network of signaling pathways that control the
differentiation of BM-MSCs into chondrocytes is simplified in the
image. There are several phases in this developmental process, such
as pre-hypertrophy, hypertrophy and proliferation. These phases are
carefully coordinated by a wide range of signaling pathways,
including the Wnt/β-catenin pathway, which stimulates chondrocyte
proliferation and differentiation; the TGF-β/SMAD pathway, which is
essential for chondrogenesis as it controls the production of ECM
and chondrocyte maturation; the BMP/SMAD pathway, which stimulates
chondrocyte differentiation and controls matrix synthesis; the Ihh
signaling pathway and PTHrP signaling pathway, which controls
chondrocyte proliferation, hypertrophy and endochondral bone
formation; the FGF signaling pathway, which stimulates both
chondrocyte proliferation and differentiation; and the MAPK
signaling pathway, which is involved in multiple chondrogenesis,
including proliferation, differentiation and matrix synthesis. It
is important to understand that these signaling pathways show
complex interactions, with feedback loops and crosstalk having a
significant impact on chondrocyte development. Developing
successful strategies for cartilage tissue engineering and repair
requires a thorough understanding of these signaling mechanisms
(35,61,64,65).
BM-MSCs, bone marrow-derived mesenchymal stem cells; TGF-β,
transforming growth factor-β; Ihh, Indian hedgehog; PTHrP,
parathyroid hormone-related peptide; FGF, fibroblast growth
factor.
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Copy and paste a formatted citation
Spandidos Publications style
Kaushalya GN and Rajapakse S: Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review). Med Int 6: 33, 2026.
APA
Kaushalya, G.N., & Rajapakse, S. (2026). Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review). Medicine International, 6, 33. https://doi.org/10.3892/mi.2026.317
MLA
Kaushalya, G. N., Rajapakse, S."Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review)". Medicine International 6.3 (2026): 33.
Chicago
Kaushalya, G. N., Rajapakse, S."Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review)". Medicine International 6, no. 3 (2026): 33. https://doi.org/10.3892/mi.2026.317
Copy and paste a formatted citation
x
Spandidos Publications style
Kaushalya GN and Rajapakse S: Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review). Med Int 6: 33, 2026.
APA
Kaushalya, G.N., & Rajapakse, S. (2026). Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review). Medicine International, 6, 33. https://doi.org/10.3892/mi.2026.317
MLA
Kaushalya, G. N., Rajapakse, S."Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review)". Medicine International 6.3 (2026): 33.
Chicago
Kaushalya, G. N., Rajapakse, S."Unveiling the potential use of bioprinting materials in directing stem cell fate for cartilage regeneration: Focusing on induced pluripotent stem cells and enhanced lubrication (Review)". Medicine International 6, no. 3 (2026): 33. https://doi.org/10.3892/mi.2026.317
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