Three-dimensional (3D) bioprinting has emerged as a powerful platform for recapitulating the structural and functional complexity of native tissues and organs. Significant progress has been achieved in the development of biomaterial-based, cell-laden bioinks and the fabrication of constructs with controlled geometries and spatial organization. These advances have enabled the production of tissue models that exhibit promising short-term biocompatibility, maintaining cell viability for several days following printing.

Despite these achievements, a critical limitation persists in the restricted cellular proliferation within the interior of printed constructs, while cells located on the external surfaces exhibit comparatively robust growth. This disparity is primarily attributed to the unfavorable microenvironment within the matrix, characterized by limited oxygen and nutrient diffusion, mechanical confinement that restricts cellular migration, and insufficient cell–cell communication. Collectively, these factors hinder the formation of an interconnected cellular network essential for functional tissue development.

This Special Issue focuses on recent advancements aimed at engineering improved microenvironments within 3D bioprinted constructs. Particular emphasis is placed on multifaceted strategies such as the incorporation of bioactive, cell-adhesive motifs, and the precise modulation of key physicochemical properties, including viscoelasticity, porosity, and matrix stiffness. These approaches are designed to enhance mass transport, facilitate cell-mediated matrix remodeling, and promote dynamic cellular interactions. Collectively, such innovations are expected to overcome current limitations and accelerate the development of functional tissue constructs, thereby advancing the translational potential of 3D bioprinting in regenerative medicine.