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International Journal of Bioprinting 3D-printed variable stiffness scaffolds

degeneration and the development of osteoarthritis over as acellular biomaterial inks, where cell attachment and
time. Therefore, there is an urgent need to develop scaffolds proliferation occur within the scaffold after implantation.
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to adequately support tissue regeneration in damaged Typical hydrogels used in meniscus regeneration include
menisci. Designing a structural and hierarchical scaffold alginate, collagen, gelatin, and gelatin methacrylate
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that mimics the architectural and mechanical features of (GelMA). GelMA scaffolds have gained attention in
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the native meniscus for supporting tissue regeneration is recent years for tissue engineering applications due to their
a significant challenge for researchers, owing to the forces retention of biological properties, such as cell adhesion
and mechanical demands the native meniscus endures. domains and enzymatic degradability. 23,24 Moreover,
Along with the load-bearing capabilities of the meniscus, GelMA is easily crosslinked, with potential in cartilage
its unique structure is essential to maintain congruency tissue engineering. 23,25
between the femoral condyles and tibial plateau. The However, currently used biomaterial inks in meniscus
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meniscal collagen structure is essential for reinforcing the tissue engineering typically lack the major compositional
tissue to withstand the loads experienced across the knee units of the native extracellular matrix (ECM), such as
joint, as it transfers forces between the femoral and tibial glycosaminoglycans (GAGs). GAGs, such as hyaluronic
joint surfaces by developing hoop stress. Radial fibers also acid (HA) and chondroitin sulfate (CS), are abundant
play a significant role, as they provide resistance to the components of the ECM in cartilage and meniscus tissue,
lateral separation of circumferential fiber bundles when participating in numerous biological processes. The
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an axial load is applied. Therefore, the development of inclusion of CS in a scaffold may promote chondrogenesis
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a biomimetic scaffold that replicates the specific three- and enhance its mechanical properties, displaying
dimensional (3D) microstructure of the meniscus is crucial promising results for cartilage tissue engineering. In
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for effective meniscus tissue engineering. contrast, HA is involved in many critical biological
Research has already been conducted on creating functions, such as regulating cell adhesion and influencing
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anatomically shaped meniscus scaffolds and replicating cell proliferation and differentiation.
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the internal collagen structure of the native meniscus. 4,6,8 This study has two main objectives. Firstly, we aim
However, there has been limited work on developing to create a novel biomimetic PCL meniscus scaffold for
regional variations within the scaffold to match the partial tissue regeneration following a traumatic injury.
heterogeneous mechanical properties of the native The scaffold has an internal structure inspired by the native
meniscus. meniscus, consisting of circumferential and radial fibers.
Synthetic materials have been studied to develop a Furthermore, the unique structure of the scaffold varies by
structural meniscus scaffold with appropriate mechanical region to match the distinct region-dependent mechanical
properties, including polyurethane (PU), polycarbonate properties of the native tissue. Secondly, we investigated
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urethane (PCU), poly-L-lactic acid (PLLA), and various GelMA/GAG composite hydrogels to develop
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polycaprolactone (PCL). Among these, PCL is one of the a biomaterial ink that mimics the natural ECM of the
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most promising materials for meniscus tissue engineering. meniscus and infiltrates into the PCL framework, followed
It plays an important role in matrix organization, augments by comprehensive in vitro analysis.
matrix content, and possesses unique physical strength
suitable for applications in hard tissue engineering, such as 2. Materials and methods
the meniscus or bone. 13,14 Furthermore, PCL is an attractive 2.1. Materials
material due to its approval by the United States (US) Food All PCL scaffolds were printed by fiber deposition of
and Drug Administration (FDA). Although synthetic molten PCL (molecular weight [MW]: 50 kD; Capa 6500D;
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PCL is biocompatible, it does not readily promote cell Perstorp, Sweden), using a pneumatic-based BioBots
proliferation. Therefore, in addition to using PCL for the bioprinter (Allevi, United States of America [USA]).
structural framework of the meniscus scaffold, a natural GelMA and the photoinitiator, lithium phenyl-2,4,6-
material should be incorporated into the PCL framework trimethylbenzoylphosphinate (LAP), were purchased from
to promote cell growth, proliferation, and differentiation, Allevi (USA). GelMA was derived from Type A, 300 Bloom,
and ultimately facilitate new tissue formation. Hydrogels porcine skin and fabricated to achieve a final degree of
are widely used in tissue engineering to promote cell methacrylation of 50%. GAGs used to create the composite
infiltration and proliferation. 15,16 The use of hydrogels biomaterials inks included HA (MW: 0.1 MDa; Shanghai
supports nutrient diffusion and can provide adhesion Easier Industrial Development, China), methacrylated HA
sites and signaling cues that guide cell growth and the (HAMA; MW: 0.1 MDa; Advanced Biomatrix, USA), and
formation of desired tissue. Hydrogels can also be 3D CS derived from shark cartilage (C4384; Sigma-Aldrich,
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printed with encapsulated cells, known as a bioink, or used USA).
Volume 10 Issue 4 (2024) 493 doi: 10.36922/ijb.3784