Photochemical 3D Printing of Bioresorbable Copolyesters for Applications in Transdermal Drug Delivery and Soft Tissue Repair

Abstract

Additive manufacturing (3D printing) enables rapid fabrication of customizable, complex structures. In vat photopolymerization (VPP) 3D printing, photoreactive resins are selectively cured by a light source in a layer-by-layer fashion to achieve three-dimensional objects. Vat photopolymerization techniques, like digital light processing (DLP) and continuous liquid interface production (CLIP), are powerful tools for the fabrication of high-resolution biomedical devices. Bioresorbable VPP resins are of clinical interest for biomedical devices because of their ability to completely degrade in vivo through natural biological pathways. However, the scope of 3D-printable, bioresorbable resins is limited.Herein, poly(propylene fumarate-co-propylene succinate) (PPFPS) copolyesters were synthesized, characterized, and 3D printed via CLIP. These fumarate-based copolyesters contain alkene moieties amenable for photochemical 3D printing and can hydrolytically degrade into bioresorbable by-products. Thiol-ene click chemistry yielded crosslinked thermosets with high control over mechanical and degradation properties. In turn, PPFPS resins were 3D printed into biomedical devices for transdermal drug delivery and soft tissue repair. Microneedle array patches (MAPs) were fabricated with precise features (< 2 mm) that effectively punctured skin. Dexamethasone-loaded MAPs demonstrated controlled elution of drug and achieved substantial relief of postoperative pain in a murine tibial fracture model. Pharmacokinetic analysis showed that local MAP administration was able to control pain at lower doses than intravenous administration. Separately, apremilast-loaded, detachable MAPs were fabricated for sustained transdermal treatment of psoriasis. Detachable needles were designed to remain embedded in the skin after application, allowing for long-term drug release. Hollow MAPs were also developed for the transdermal delivery of anti-itch therapeutics. Each hollow microneedle has a void space that can be loaded with a variety of liquid-state or solid-state cargo, such as small molecule lipids. Finally, novel anchor clip devices were developed for soft tissue repair. These anchor clips serve as a bioresorbable, knotless anchoring strategy for securing sutures in high-tension soft tissue wounds. The anchor clips showed satisfactory in vivo biocompatibility in a porcine abdominal implantation model. Overall, this work highlights the development of bioresorbable PPFPS-based resins for photochemical 3D printing and illustrates their potential for clinically-relevant applications.