Enzyme‐Regulated Extended Swelling of Hydrogels for Dehiscence‐Less Tissue Expansions

Abstract Tissue expansion is traditionally achieved by injecting saline into an implanted silicone balloon via external tubing, which causes patient discomfort. Hydrogels eliminate the need for tubing due to their self‐swelling properties, but they fail to prevent suture wound dehiscence due to immediate swelling after implantation. Here, the concept of “extended swelling” in an interpenetrating hydrogel network is introduced to avoid dehiscence. The hydrogel consists of enzymatically degradable hyaluronic acid (HA) networks and non‐degradable polyacrylic acid (PAAc) networks. The gel remains structurally intact until suture wound healing after implantation by the constraint of the HA networks on the PAAc networks. Upon hyaluronidase (HYAL) injection, the HA networks degrade, initiating the extended swelling after which enzymatic degradation controls its onset and rate. Furthermore, the generalized ideal elastomeric gel model is employed to understand the extended swelling process. The model predicts the maximum extended equilibrium swelling ratio in vivo, confirming the hydrogel's ability to generate sufficient pressure while preventing overexpansion beyond the tissue rupture threshold. The theoretical framework aligns with experimental observations, demonstrating that the tissue expansion is induced by yes1‐associated protein (YAP1)‐mediated epidermal proliferation. This approach establishes its potential as a next‐generation tissue expander for clinical applications.