An Osteoimmunomodulatory Biopatch Potentiates Stem Cell Therapies for Bone Regeneration by Simultaneously Regulating IL‐17/Ferroptosis Signaling Pathways

Currently, there are still great challenges in promoting bone defect healing, a common health problem affecting millions of people. Herein an osteoimmunity‐regulating biopatch capable of promoting stem cell‐based therapies for bone regeneration is developed. A totally biodegradable conjugate is first synthesized, which can self‐assemble into bioactive nano micelles (PPT NMs). This nanotherapy effectively improves the osteogenesis of periodontal ligament stem cells (PDLSCs) under pathological conditions, by simultaneously regulating IL‐17 signaling and ferroptosis pathways. Incorporation of PPT NMs into biodegradable electrospun nanofibers affords a bioactive patch, which notably improves bone formation in two rat bone defect models. A Janus bio patch is then engineered by integrating the bioactive patch with a stem cell sheet of PDLSCs. The obtained biopatch shows additionally potentiated bone regeneration capacity, by synergistically regulating osteoimmune microenvironment and facilitating stem cell differentiation. Further surface functionalization of the biopatch with tannic acid considerably increases its adhesion to the bone defect, prolongs local retention, and sustains bioactivities, thereby offering much better repair effects in rats with mandibular or cranial bone defects. Moreover, the engineered bioactive patches display good safety. Besides bone defects, this osteoimmunity‐regulating biopatch strategy can be applied to promote stem cell therapies for spinal cord injury, wound healing, and skin burns. A Janus biopatch is engineered by integrating a nanofibrous membrane containing an inflammation‐resolving nanotherapy and a stem cell sheet. Synergistic osteoimmunomodulatory effects and stem cell therapies for bone regeneration are achieved and demonstrated in rats with mandibular and cranial defects, by simultaneously regulating IL‐17/ferroptosis signaling. This bioactive bilayer strategy is promising for potentiating stem cells to treat inflammatory bone diseases.