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A microdevice that offers glucagon supplements in a safe, non-invasive, and glucose-responsive manner is ideal for avoiding fatal hypoglycemia consequences from insulin overdosage during daily diabetes treatment. However, mold-assisted microfabrication of biomedical materials or devices typically needs high-resolution laser ablation to scale down structural design. In addition, the majority of the polymeric drug delivery materials being used to fabricate devices are dissolvable or deformable in aqueous environments, which restricts washing-based cleaning and purification procedures post shape fixation. This study leverages the design flexibility of 3D printing-assisted mold casting and presents a shrinking microfabrication approach that allows subsequent washing procedures to remove toxic monomer residues during polymerization. The feasibility of this approach is demonstrated by developing a glucose-responsive transdermal glucagon microneedle patch through matrix volume change-mediated release kinetic control. Shown in the type 1 diabetic mouse model, this transdermal patch can reverse the occurrence of hypoglycemia while lowering the risk of monomer residue-induced irritation during treatment. Freeing from the restrain of molding resolution for microstructure design, this shrinking methodology further provides an insight into post-fabrication purifications of biomedical materials.

Abstract A microdevice that offers glucagon supplements in a safe, non‐invasive, and glucose‐responsive manner is ideal for avoiding fatal hypoglycemia consequences from insulin overdosage during daily diabetes treatment. However, mold‐assisted microfabrication of biomedical materials or devices typically needs high‐resolution laser ablation to scale down structural design. In addition, the majority of the polymeric drug delivery materials being used to fabricate devices are dissolvable or deformable in aqueous environments, which restricts washing‐based cleaning and purification procedures post shape fixation. This study leverages the design flexibility of 3D printing‐assisted mold casting and presents a shrinking microfabrication approach that allows subsequent washing procedures to remove toxic monomer residues during polymerization. The feasibility of this approach is demonstrated by developing a glucose‐responsive transdermal glucagon microneedle patch through matrix volume change‐mediated release kinetic control. Shown in the type 1 diabetic mouse model, this transdermal patch can reverse the occurrence of hypoglycemia while lowering the risk of monomer residue‐induced irritation during treatment. Freeing from the restrain of molding resolution for microstructure design, this shrinking methodology further provides an insight into post‐fabrication purifications of biomedical materials.