Porous Se@SiO2 nanoparticle composite hydrogels loaded with adipose stem cells improves the local microenvironment to promote rotator cuff tendon–bone healing in rats

Abstract

Functional repair of the tendon–bone interface poses significant challenges in clinical practice; furthermore, identifying methods to enhance healing at enthesis is a central concern in regenerative medicine. The application of stem cells in the healing process of interface injuries is widespread; however, direct injection of stem cells into this interface leads to significant losses of many stem cells. Oxidative stress significantly influences interface repair, and the role of selenium in mitigating oxidative stress and regulating inflammation has been demonstrated. This study utilised gelatine methacrylate (GelMA) as a stem cell transporter, while porous Se@SiO₂ nanoparticles (Se@SiO₂ NPs) were incorporated to change the interface microenvironment and facilitate the repair of the tendon–bone interface. Oxidative stress effects were analysed using flow cytometry, immunofluorescence staining, and qRT-PCR. The repair of the enthesis was assessed using histological staining, biomechanical evaluation, and MRI. Se@SiO₂ NPs significantly reduced the expression of inflammation-related markers in an in vitro oxidative stress model. Additionally, porous selenium nanocomposite hydrogels loaded with adipose stem cells were implanted into the rat tendon–bone interface. At eight weeks following the procedure, the enthesis exhibited superior collagen fibre continuity and orientation, enhanced bone and fibrocartilage production, and biomechanical functions that were substantially greater than those of the comparison group. This study demonstrates that porous Se@SiO₂ NP composite hydrogels with antioxidant and anti-inflammatory properties provide a supportive environment for transplanted stem cells and promote tissue repair.