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their survival and proliferation through enabling the passage of required nutrients for cells to

survive at the PMs core. Among various polymers from natural and synthetic sources, poly(lactic-

co-glycolic acid) (PLGA), a synthetic polymer approved by FDA, has garnered enormous interest

in the field of biomaterials due to the favorable mechanical properties, low toxicity, and low

immunogenicity 28,29 . It has been demonstrated that the cells are attached more rapidly to the PLGA-

based PMs with a significantly enhanced growth rate compared to the commercially available

porcine gelatin microcarriers 27,30-32 . Moreover, it should be noted that these PMs can be applied for

drug delivery towards joint diseases. In a case, Kaamini designed the rapamycin encapsulated

PLGA-based PMs, which demonstrated high residence time and co-localization with various joint

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tissues when administered in the mice knee via intra-articular injections . Such biomaterial-based
delivery of rapamycin offered great potential for testing in animal models and clinical translation

as a patient compliant treatment. The controllable spatial distribution of microsphere-based

scaffolds could mimic the native tissues and thus form bone-like and cartilage-like macro-sized

architectures 34-36 . Gelatin methacryloyl (GelMA) hydrogel has emerged as an ideal biomaterial for

3D bioprinting owing to its photo-crosslinkability, excellent biocompatibility, and tunable

mechanical properties. Studies have demonstrated that the density of the molecular network (DMN)

of GelMA can be precisely modulated by optimizing the degree of substitution and solid content,

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enabling its compressive modulus to span a wide range of 3-123 kPa . This versatility allows

GelMA to match the mechanical characteristics of various soft tissues such as liver, brain, and

kidney. Furthermore, by incorporating reinforcing materials, GelMA-based composites can

approach the mechanical requirements of stiffer tissues, including cartilage and bone. The innate

RGD sequences in GelMA support cell adhesion and migration. Low-DMN formulations facilitate

cell spreading and proliferation, supporting high cell viability (>95%), while high-DMN versions

offer enhanced shape fidelity and mechanical stability, making them suitable for printing complex

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