Vat photo-polymerization 3D printing of gradient scaffolds for osteochondral tissue regeneration

In recent decades, osteochondral (OC) tissue regeneration has been one of the major challenges in regenerative medicine. The absence of blood vessels, lymphatic vessels, and nerves in OC tissue prevents self-repair, while the structural complexity and differences between bone and cartilage layers make conventional surgical treatments largely ineffective. To address this issue, tissue engineering has emerged as a promising approach to replacing damaged OC tissue, with a particular focus on innovative strategies such as the design of continuous gradient scaffolds that mimic the complex architecture of native OC tissue. In this review vat photopolymerization (VPP) 3D printing technologies are presented as one of the most effective methods for fabricating gradient scaffolds for OC tissue repair. By leveraging photochemical reactions and light-assisted techniques, such as digital light processing (DLP), stereolithography (SLA) and two-photon polymerization (2-PP), highly precise porous structures made of biocompatible photo-crosslinkable resins have been successfully fabricated, with several relevant examples reported herein. DLP, SLA and 2-PP have proven fundamental in creating compositional, architectural, and mechanical gradients within scaffolds. Moreover, scaffold functionalization with bioactive molecules has demonstrated effectiveness in repairing damaged OC tissue in both in vitro and in vivo conditions. Moreover, the adoption of modeling tools such as the design of experiments (DoE) approach and AI-driven computational methods has proven to be valuable in optimizing the fabrication process and enhancing scaffold designs to more closely replicate the architecture and functionality of osteochondral tissues. Statement of significance: Despite the transformative potential of vat photopolymerization (VPP) techniques, such as stereolithography (SLA) and digital light processing (DLP), for developing high-precision gradient 3D scaffolds for osteochondral (OC) tissue repair, achieving full biomimetic restoration remains a significant challenge. This review offers a comprehensive analysis of advancements in VPP, detailing how these techniques enable precise control over scaffold composition, architecture, and mechanical properties to closely replicate the complex structure of OC tissue. Furthermore, it underscores the critical need for standardized protocols and long-term evaluations in scaffold development. Addressing these gaps is essential to advancing the clinical translation of VPP-based scaffolds, paving the way for more effective treatments for OC tissue damage.