Engineered Exosome-Functionalized Extracellular Matrix-Mimicking Hydrogel for Promoting Bone Repair in Glucocorticoid-Induced Osteonecrosis of the Femoral Head

Abstract

Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) is a serious bone disease that often affects young individuals. Bone grafting combined with core decompression is mainly used in the clinic to treat GC-ONFH. However, the outcome is usually not satisfactory, as expected. Here, we report an engineered exosome-functionalized extracellular matrix-mimicking hydrogel for promoting bone repair in GC-ONFH. Compared with Con-Exo, exosomes secreted by bone marrow stem cells (BMSCs) in conventional culture medium, the engineered Li-Exo, exosomes derived from bone marrow stem cells (BMSCs) stimulated by lithium ions, promoted macrophage M2 polarization while inhibiting macrophage M1 polarization. Furthermore, inspired by the fact that hydrogels can serve as desirable carriers of exosomes to facilitate their release in a sustained manner for improved therapeutic efficiency and in vivo application, an extracellular matrix (ECM)-mimicking hydrogel (Lightgel) composed of methacryloylated type I collagen was employed to incorporate Li-Exo/Con-Exo to construct the Lightgel-Li-Exo hydrogel/Lightgel-Con-Exo hydrogel. In vitro studies showed that the Lightgel-Li-Exo hydrogel had the most significant pro-osteogenic and pro-angiogenic activity. Finally, we evaluated the therapeutic effects of the hydrogel in rat models of GC-ONFH. As a result, the Lightgel-Li-Exo hydrogel had the most significant effect on enhancing macrophage M2 polarization, osteogenesis, and angiogenesis to promote bone repair in GC-ONFH. Taken together, this novel engineered exosome-functionalized ECM-mimicking hydrogel could be a promising strategy for osteonecrosis treatment.

Immunomodulatory hydrogels for skin wound healing: cellular targets and design strategy

“…Hydrogels have long been attracting considerable interest in skin wound dressings owing to their diverse properties such as moisture retention, extracellular matrix resembling structure, and function as delivery carriers. 105–110 For wound healing, in order to modulate the immunoregulatory cells and stimulate immune responses, multiple hydrogels have been designed with the aim of balancing inflammatory cell infiltration, 111,112 tuning macrophage polarization, 113 promoting cell proliferation and migration, 114 and regulating collagen remodeling by controlling their physicochemical properties. 115 Physical properties such as dimensionality, stiffness, porosity, topography, electrical properties, and wettability have been revealed to modulate the immune response.…”

Metal Ion-Containing Hydrogels: Synthesis, Properties, and Applications in Bone Tissue Engineering

“…Copyright 2019 Materials Science & Engineering, C. (E) Schematic illustration of engineering exosome-functionalized ECM-mimicking and Li + -containning hydrogels for promoting bone repair. Adapted with permission from ref . Copyright 2023 ACS Applied Materials & Interfaces.…”

Ion incorporation into bone grafting materials

“…Furthermore, exosomes from lithium ion-stimulated bone marrow stem cells have been observed to foster bone tissue repair, mainly by augmenting macrophage M2 repolarization, which in turn advances osteogenesis and angiogenesis. [49][50][51] This has induced the integration of lithium ions in the design of tissue engineering scaffolds for bone defect repair and osteochondral interface reconstruction. 51,52 Additionally, lithium ions have demonstrated antimicrobial attributes, expedited the healing timeline for apical periodontitis, and influenced bone immunity and metabolism via the Wnt/β-catenin signaling pathway, highlighting promising potential of using lithium-infused materials for periodontal tissue regeneration.…”