In situ bioorthogonal anchoring of stem cells to conductive nanofibrils for enhanced myocardial infarction repair

초록

Numerous efforts have been made to recover damaged myocardial infarction tissue with stem cells; however, poor differentiation and low viability of transplanted cells impede effective recovery of cardiac performance. We surface-engineered polymeric nanofibrils (NFs) to be electrically conductive and bioorthogonal click chemistryreactive to improve the anchorage and performance of cardiac stem cells. Electrospun polycaprolactone nanofibers were hydrolyzed into NFs, followed by layer-by-layer coating with branched polyethylenimine and graphene oxide. The decorated NFs were then functionalized with a dibenzocyclooctyne (DBCO) group to endow them with azide (AZ) reactivity, and were subsequently reduced to retrieve electrical conductivity. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were functionalized with AZ groups via metabolic glycoengineering of unnatural N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz), rendering it capable of DBCO reactivity. The DBCO-conjugated, reduced graphene oxide-decorated NFs (preClick-rGO@NFs) and preClick-CMs were co-injected as a freshly mixed suspension into the myocardial infarction area, where cell-NF complexes formed in a manner consistent with bioorthogonal coupling. This approach improved early retention of the implanted cells within the infarcted myocardium and enhanced recovery of cardiac function. Thus, we envision that surface-decorated powdery NFs and cell transplantation can contribute to improved cardiac performance through a simple surgery.

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