Oxidation-degradable resins for 3D-printing of cell-responsive biomaterials

Additive manufacturing, or 3D printing, has emerged as a powerful tool for rapidly generating tissue engineering constructs with complex architectures. While hydrolysis-sensitive polyesters are most commonly used to 3D print these scaffolds, once implanted, these materials often degrade prematurely before tissue regeneration is achieved. To address these limitations, this study introduces new oxidation-sensitive resins that can be 3D-printed into implants designed to selectively degrade when exposed to cell-produced reactive oxygen species (ROS). Although these ROS-triggerable polymers have shown promise for matching tissue growth with implant degradation, they have yet to be adapted into simple, low-cost formulations compatible with commercial 3D printers. Here, UV-photopolymerizable, ROS-sensitive resins were created from synthesized thioketal (TK) dithiols and commercial alkene crosslinkers. A novel small-scale screening method was developed to determine each resin's optimal concentrations of photo-initiator and inhibitor. All TK resins supported fine-detail 3D printing, exhibited negligible in vitro cytotoxicity, and displayed tunable mechanical properties and oxidative sensitivity based on their respective chemistries. Finally, 3D-printed TK scaffolds implanted subcutaneously in rats underwent significant biodegradation over 4 weeks and fostered more rapid tissue infiltration than 3D-printed polyester controls. These findings highlight the potential of oxidation-sensitive resins for creating cell-responsive, tissue-regenerating medical implants with complex architectures.