A Reconfigurable\nProangiogenic Hydrogel Patch Enabling\nMinimally Invasive Drug Delivery

Hydrogel is widely used for the sustained delivery of\nbioactive\nmolecules that can treat various injuries, diseases, and tissue defects.\nHowever, inserting hydrogel implants without disrupting their functionality\nand microstructure often requires a large incision, leading to potential\ncomplications, such as infection, scarring, and pain. The gel implant\nis often manually rolled and inserted through a catheter for a minimally\ninvasive delivery. However, success heavily depends on the user’s\nskills, which can inadvertently damage the implant. To address this\nissue, we developed a reconfigurable hydrogel patch that can self-fold\ninto a small tube and unfold spontaneously after implantation through\na catheter. The hydrogel path was assembled by layering a drug-releasing\npoly­(ethylene glycol) diacrylate (PEGDA) hydrogel sheet onto a PEGDA\nand polyethylenimine (PEI) hydrogel sheet, which rapidly swells and\ndegrades homogeneously at controlled rates. The dynamics of the self-folding\nand unfolding process could be controlled by differences in the expansion\nratio and elastic modulus between the two gel layers according to\na mathematical model that closely matched experimental results. The\nunfolding process triggered a sustained release of the protein cargo.\nSpecifically, the reconfigurable gel loaded with angiopoietin 1 significantly\nenhanced neovascularization, nearly doubling the vascular density\ncompared to the control group following implantation through a tube\nwith 15% smaller diameter than the original shape of the gel patch.\nThis gel biopatch will be broadly useful for the minimally invasive\ndelivery of a wide array of therapeutic molecules, potentially enhancing\ntherapeutic outcomes.