A Multiaxial Bioreactor Integrated with an Environmental Monitoring System for Tissue-Engineered Skin Grafts

Tissue-engineered skin grafts have emerged as promising treatment options for chronic wounds. To precondition these grafts for promoting maturation, skin bioreactors have been utilized to provide mechanical stimulation. However, most conventional skin bioreactors are limited to either uni- or bi-directional stretching of the graft construct and lack mechanisms for monitoring tissue maturity, leading to uneven tissue maturation. In this study, we introduce a novel multiaxial bioreactor system that provides uniform stretching of skin grafts with continuous environmental monitoring capabilities. To achieve multiaxial stretching, we utilized a Hoberman ring design, which transforms linear actuator motion into a radial force applied to the skin graft. Skin grafts stretched using the Hoberman ring-based multiaxial system exhibited uniform cellular distribution and orientation, with user-controlled strain verified by surface area expansion. The bioreactor was designed to allow for continuous environmental monitoring with integrated sensors for pH, dissolved oxygen (DO), glucose, lactate, and media level for air-liquid interface (ALI). Furthermore, skin tissue maturation was induced by cyclic multiaxial stretching, as demonstrated by enhanced proliferation of dermal fibroblasts and improved integrity of epidermal keratinocytes. These findings indicate that the presented multiaxial bioreactor provides a simplified and robust platform for advancing regenerative medicine applications.