Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling

Abstract

Background Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. Results In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs’ stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. Conclusions PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP. Graphical Abstract

The Potential of Exosomes for Osteoporosis Treatment: A Review

“… 58 , 59 After isolating PL-derived exosomes (PL-exo) to enhance platelet-derived growth factors (GFs), DSPE-PEG-grafted alendronate (ALN) conjugated PL-exo exosomes (PL-exo-ALN) to create bone-targeting delivery of platelet lysate exosomes (PL-exo-ALN). 60 This work showed that PL-exo-ALN could reverse GCs and that it prevented the angiogenesis of BMSCs and endothelial progenitor cells (EPCs) in vitro. 60 Furthermore, through promoting bone anabolism and angiogenesis in rats, intravenous injection of PL-exo-ALN might also effectively reverse GCs-induced osteoporosis (GIOP).…”

“… 60 This work showed that PL-exo-ALN could reverse GCs and that it prevented the angiogenesis of BMSCs and endothelial progenitor cells (EPCs) in vitro. 60 Furthermore, through promoting bone anabolism and angiogenesis in rats, intravenous injection of PL-exo-ALN might also effectively reverse GCs-induced osteoporosis (GIOP). 60 …”

Targeted exosome-based nanoplatform for new-generation therapeutic strategies

“…A combination of biomaterials can enable exosomes to acquire new targeting abilities and improve their functions. In addition, another non-covalent modification strategy can be used, which involves inserting amphipathic molecules into exosomes [169][170][171]. Kim et al have inserted 1,2dioleoyl glycero-3-phosphoethanolamine with PEGconjugate (DSPE-PEG) into the exosome membrane.…”

Unlocking the potential of exosomes: a breakthrough in the theranosis of degenerative orthopaedic diseases

“…Subsequently, these exosomes were integrated with alendronate (ALN)-grafted polyethylene glycol phospholipid (DSPE-PEG-ALN), resulting in the creation of bone-targeted PL exosomes (PL Exo ALN). This innovative formulation has shown efficacy in mitigating glucocorticoid-induced osteoporosis in vivo ( Zheng et al, 2022b ). To stimulate bone formation and facilitate the healing of defects in osteoporotic rat femoral neck canal defect models, Qayoom utilized a carrier comprising calcium sulfate/nano hydroxyapatite-based nano-cement to deliver recombinant human bone morphogenetic protein-2, zoledronate, and exosomes derived from BMSCs ( Qayoom et al, 2020 ).…”