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International Journal of Bioprinting DEX-Loaded PLGA microspheres enhance cartilage regeneration

rib cartilage scaffolds are associated with postoperative release over time. Moreover, the quantity of MPs can
pain, pneumothorax, chest wall deformities, and other be tailored to meet the patient’s requirements, allowing
complications. In light of these shortcomings, tissue for personalized drug dosing and individualized
engineering offers a promising and minimally invasive treatment strategies. Furthermore, current research
alternative for addressing auricular deformities. Thus, indicates that MPs can serve as microcarrier systems
there is an urgent need for the design of tissue-engineered for cell suspension culture and for tissue defect repair
cartilage scaffolds. 2–4 by injecting individual MPs or constructs containing

The fabrication of tissue-engineered ears presents cells and MPs into the affected area. 22,23 Poly (lactic-co-
multifaceted challenges, with the restricted formation glycolic acid) (PLGA) holds a prominent position in
of cartilage tissue and the inability to maintain tissue the medical field, particularly in drug delivery systems,
shape being the prominent concerns. These hurdles are where drugs can be encapsulated within MPs and released
further compounded by inflammatory reactions, which through micropores into target tissues for sustained
24,25
result in suboptimal tissue integrity and compromised and controlled release. Additionally, PLGA MPs
mechanical properties. Hence, mitigating inflammatory can function as integral elements of tissue engineering
5,6
scaffolds, offering structural support, fostering cell
reactions during tissue formation is vital for enhancing adhesion and proliferation, and leaving behind newly
cartilage regeneration and bolstering the overall formed tissue after gradual degradation. In various
mechanical robustness of tissue-engineered ears. tissue engineering applications such as bone, cartilage,
7–9
Additionally, the insufficient mechanical properties of and muscle regeneration, PLGA MPs play pivotal roles
the materials utilized in tissue engineering contribute to in fostering tissue regeneration and repair. 26,27 With their
the challenges encountered in achieving desired tissue multifunctionality and controlled release characteristics,
formation outcomes. These material constraints highlight PLGA MPs offer potent tools for both tissue engineering
the significance of developing strategies to enhance the and drug delivery applications. The multifunctionality
mechanical performance of tissue-engineered constructs and controlled release characteristics make them powerful
while simultaneously mitigating inflammatory responses tools for both tissue engineering and drug delivery
to facilitate successful tissue regeneration. 10
applications. Moreover, they address the challenge of
Currently, extrusion-based three-dimensional (3D) simultaneous printing with cells, a hurdle faced by other
bioprinting technology is widely used in tissue engineering thermoplastic synthetic polymers. The addition of PLGA
to fabricate complex 3D biological structures. 11–13 MPs successfully resolves the printability issue with seed
This technology enables precise control over complex cells, a common limitation with other thermoplastic
structures and functions through layer-by-layer deposition synthetic polymers. Unlike polycaprolactone (PCL),
of biodegradable bioinks, allowing the construction of which necessitates high-temperature printing, PLGA
customized structures. 14 MPs can be mixed with gelatin methacryloyl (GelMA)
Dexamethasone (DEX) is a synthetic corticosteroid hydrogel and seed cells at room temperature after
widely utilized in clinical medicine. 15,16 It exerts various preparation and sterilization. This mixture can be directly
crucial physiological and pharmacological effects, used for constructing tissue-engineered cartilage,
28,29
including potent anti-inflammatory, immunosuppressive, facilitating effective cell adhesion.
and anti-allergic properties. DEX finds application in In this study, we loaded DEX at various concentrations
the management of inflammatory diseases, autoimmune into PLGA MPs, which were used as a material for
diseases, allergic conditions, and other medical issues. cartilage construction. We examined its effectiveness in
Additionally, it is commonly included as a supplement in reducing inflammatory responses and promoting cartilage
chondrocyte culture media. While DEX presents potent tissue regeneration. The general flow of the experiments
anti-inflammatory benefits, it entails a wide range of side described in this paper is schematically illustrated and
effects, such as elevated risk of hypertension, diabetes, and presented in Figure 1.
osteoporosis. 17,18 To enhance efficacy and reduce systemic
side effects of DEX, local sustained release methods can be 2. Materials and methods
adopted to achieve the most optimal trade-off between its 2.1. Materials
advantages and shortcomings.
The chemical reagents used in the experiments,
Porous microspheres represent an optimal drug including PLGA (50:50), DEX lyophilized powder (MW:
delivery vehicle due to their substantial pore-to-surface 392.47), polyvinyl alcohol (PVA; MW: 30,000–70,000),
ratios and interconnected pores. 19–21 One of the primary GelMA lyophilized powder, and lithium phenyl-2,4,6-
benefits of MP drug delivery is their ability to sustain trimethylbenzoylphosphinate (LAP; 2.5% w/v) solution

Volume 10 Issue 5 (2024) 384 doi: 10.36922/ijb.3396