DLP 3D printing of hyperelastic photocurable perivascular scaffolds enabling patient-specific vascular remodeling

Photopolymerization-based 3D printing, enabled the fabrication of complex, patient-specific scaffolds with high resolution and spatial precision. However, most photocurable biomaterials exhibited mechanical mismatch with soft tissues such as vascular, cartilage, and tendon tissues. To address this limitation, we developed a biodegradable and elastomeric resin (A-PLCL/4SH), composed of methacrylate-functionalized poly(L-lactide-co-ε-caprolactone) (A-PLCL) and pentaerythritol tetra(3-mercaptopropionate) (PETA-4SH), which enabled high-fidelity digital light processing (DLP) 3D printing. Using this resin, we fabricated a dual-layered perivascular scaffold (BioShell) for arteriovenous fistula (AVF) intervention, that integrating mechanical support, hemodynamic optimization, and localized drug delivery. BioShell consisted of a DLP-printed A-PLCL/4SH outer layer (BioCore) and an inner layer of methacrylated silk fibroin (SilMA) hydrogel, which enabled dual-phase release of 4‑hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA). The initial burst release of TEMPOL scavenged reactive oxygen species (ROS) and mitigated early inflammation, while sustained TEMPOL/RAPA release inhibited vascular smooth muscle cell (VSMC) proliferation and neointimal hyperplasia (NIH). Compared to metallic wraps (e.g., VEST/VasQ) and traditional electrospun scaffolds, BioShell uniquely integrated compliance-matched elasticity, programmable drug release, and patient-specific fabrication. Fluid-structure interaction simulations confirmed improved hemodynamics and reduced wall stress. In vitro and in vivo evaluations demonstrated effective ROS clearance, suppressed VSMC proliferation, and enhanced vascular remodeling. Overall, BioShell represents a modular and clinically relevant platform for AVF therapy and broader soft tissue reconstruction. STATEMENT OF SIGNIFICANCE: We developed a dual-layer perivascular scaffold (BioShell) that combined mechanical support with programmable drug delivery. By integrating a 3D printed elastic outer shell (A-PLCL/4SH) with an injectable SilMA hydrogel layer, BioShell achieved high compliance matching with native vessels, overcoming the stiffness and limited therapeutic functionality of metallic and electrospun wraps. In vivo, BioShell/RAPA reduced stenosis by ∼77 % compared to control and significantly outperformed non-drug-loaded scaffolds (p < 0.001) in promoting vascular remodeling. This modular, biodegradable system offered a translational strategy for vascular reconstruction and soft tissue repair.