Design and Characterization of a Therapeutic Non-phospholipid Liposomal Nanocarrier with Osteoinductive Characteristics To Promote Bone Formation

Abstract

Sterosomes are a recently developed type of non-phospholipid liposomes formed from single-chain amphiphiles and high content of sterols. Although sterosomes presented significantly increased stability compared to conventional phospholipid liposomes, current sterosome biomaterials are not truly bioactive and have no intrinsic therapeutic effects. The purpose of this study was to develop a sterosome formulation with osteoinductive properties by an effective selection of sterol, one of the sterosome components. Oxysterols are oxidized derivatives of cholesterol and are known to stimulate osteogenesis and bone formation. Thus, 20S-hydroxycholesterol (Oxy), one of the most potent oxysterols for bone regeneration was examined as a promising candidate molecule to form fluid lamellar phases with a single-chain amphiphile, namely stearylamine (SA). First, the optimal composition was identified by investigating the phase behavior of SA/Oxy mixtures. Next, the capacity of the optimized SA/Oxy sterosomes to promote osteogenic differentiation of bone marrow stromal cells was assessed in vitro in a hydrogel environment. Furthermore, we explored the effects of osteogenic oxysterol sterosomes in vivo with the mouse critical-sized calvarial defect model. Our results showed that SA/Oxy sterosomes induced osteogenic differentiation in vitro and enhanced calvarial healing without delivery of additional therapeutic agents, indicating their intrinsic bone forming potential. This study suggests a promising non-phospholipid liposomal platform with osteoinductive properties for delivery of small molecular drugs and/or other therapeutic genes for enhanced bone formation.

Smoothened agonist sterosome immobilized hybrid scaffold for bone regeneration

“…1A). Sterosome presents an inherent osteoinductive property occurring from OHC even without drug loading (19). OHC is a naturally occurring oxysterol and dictates pro-osteogenic and anti-adipogenic lineage commitment in mesenchymal stem cells (MSCs) by binding smoothened and activating hedgehog signaling (20,21).…”

Design of hydrogels to stabilize and enhance bone morphogenetic protein activity by heparin mimetics

“…After 24 h, the medium was replaced with the mixture of CM (180 µL) and 1× polysulfonate solution (20 µL). The polysulfonates were tested in various concentrations ranging from 0.1× (6.5, 0.26, and 2.9 µM for PVSA, PSS, and Hep, respectively) to 10× (655, 26, and 290 µM for PVSA, PSS, and Hep, respectively) The cell viability was measured by following equation (1) after alamarBlue (Thermo Fisher Scientific, CA) assay as previously described[43]. In brief, BMSCs were cultured in CM containing polysulfonate 1× solution for 24 h and the medium was replaced with 10% (v/v) alamarBlue reagent in CM.…”

Apatite‐Binding Nanoparticulate Agonist of Hedgehog Signaling for Bone Repair

“…First, 20S‐OHC/PA STs were prepared by the self‐assembling of 20S‐OHC and PA under the ultrasonic environment, and 5% of their peripheral groups (COOH) were decorated with HA‐binding Alt via the condensation reaction to obtain Alt‐modified sterosomes (ASTs) . The average size of STs detected with dynamic light scattering (DLS) was decreased from 131.2 to 94.2 nm after modification with Alt (Figures S1 and S2, Supporting Information).…”

“…Current nanoparticles are employed primarily as carrier platforms to enhance the biological effects of cargos and overcome the aforementioned drawbacks associated with therapeutic agents . However, nanoparticles themselves lack biological activities and have no therapeutic effects in the treatment of tissue defects . Therefore, our promising strategy is toward developing multifunctional nanoparticles with intrinsically osteoinductive characteristics that could maximize hedgehog signaling activity in the defect site.…”