Brick by Brick the Wall Is Being Built: Particle-Based Scaffolds for Regenerative Medicine.

Tissue engineering offers a promising solution by developing scaffolds that mimic the extracellular matrix and guide cellular growth and differentiation. Recent evidence suggests that scaffolds must provide not only biocompatibility and appropriate mechanical properties, but also the structural complexity and heterogeneity characteristic of natural tissues. Particle-based scaffolds represent an emerging paradigm in regenerative medicine, wherein micro- and nanoparticles serve as primary building blocks rather than minor additives. This approach offers exceptional control over scaffold properties through precise selection and combination of particles with varying composition, size, rigidity, and surface characteristics. The presented review examines the fundamental principles, fabrication methods, and properties of particle-based scaffolds. It discusses how interparticle connectivity is achieved through techniques such as selective laser sintering, colloidal gel formation, and chemical cross-linking, while scaffold architecture is controlled via molding, templating, cryogelation, electrospinning, and 3D printing. The resulting materials exhibit tunable mechanical properties ranging from soft injectable gels to rigid load-bearing structures, with highly interconnected porosity that is essential for cell infiltration and vascularization. Importantly, particle-based scaffolds enable sophisticated pharmacological functionality through controlled delivery of growth factors, drugs, and bioactive molecules, while their modular nature facilitates the creation of spatial gradients mimicking native tissue complexity. Overall, the versatility of particle-based approaches positions them as prospective tools for tissue engineering applications spanning bone, cartilage, and soft tissue regeneration, offering solutions that integrate structural support with biological instruction and therapeutic delivery on a single platform.