Electrosprayed Regeneration‐Enhancer‐Element Microspheres Power Osteogenesis and Angiogenesis Coupling

Abstract

Electrosprayed microspheres for bone regeneration are conventionally restricted by the lack of osteogenic modulation for both encapsulated stem cells and surrounding cells at the defect site. Here, sodium alginate microspheres encapsulating L‐arginine doped hydroxyapatite nanoparticles (Arg/HA NPs) and bone mesenchymal stem cells (BMSCs) as regeneration‐enhancer‐element reservoirs (Arg/HA‐SA@BMSC) for bone healing are electrosprayed. The Arg/HA NPs serve as a container of L‐arginine and Ca2+ and the BMSCs inside the microspheres metabolize the released L‐arginine into bioactive gas nitric oxide (NO) in the presence of Ca2+ to activate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Meanwhile, the generated NO diffuses out of the microspheres together with the Ca2+ and L‐arginine as exterior enhancers to promote the osteogenesis–angiogenesis coupling of surrounding BMSCs and endothelial cells (ECs) at the bone defect site, generating an internal/external modulation loop between the encapsulated cells and surrounding native cells. It is demonstrated that such regeneration‐enhancer‐element reservoirs could effectively increase the bone tissue formation and neovasculature using rat calvarial defect models. It is envisioned that the microsphere system could streamline vascularized bone regeneration therapy as a high throughput, minimally invasive yet highly effective strategy to accelerate bone healing.

Electrospun nanofibers for bone regeneration: from biomimetic composition, structure to function

“…Moreover, the produced NO also diffused out of the microspheres and acted as an exterior enhancer to further facilitate the angiogenesis and osteogenesis coupling of surrounding ECs and BMSCs at the bone defect sites. 277 In their another study, such a wellcoordinated osteogenic-angiogenic coupling effect by sustained activation of NO related signaling pathway was also achieved for bone regeneration of electrospun nanofibers. 278 As an emerging technology similar to electrospinning, electrospraying can be employed to deposit nanostructured materials on electrospun nanofibers in the same electric field to realize multifunctionality.…”

“…12A). 277 In this system, L-arginine, together with Ca 2+ , could release from the nanoparticles, and then was 265 Copyright 2016, Royal Society of Chemistry. (B) Schematic of electrospinning and the 3D printing hybrid bilayer scaffold for guided bone regeneration.…”

“…12A). 277 In this system, l -arginine, together with Ca 2+ , could release from the nanoparticles, and then was metabolized into NO gas by BMSCs inside the microspheres. NO is a bioactive gas to work as an endogenous signaling molecule to simultaneously stimulate the angiogenic and osteogenic cascades in bone repair.…”

“…Reproduced with permission. 277 Copyright 2022, Wiley-VCH. (B) Design of the honeycomblike scaffolds by combining electrospinning with electrospraying.…”

Calcium Phosphate-Based Biomaterials for Bone Repair

“…Ca 2+ is also capable of forming and maturing bone tissue by calcification. Ca 2+ influence the bone cell maturation and bone tissue regeneration by regulating related cellular signaling pathways [ 50 , 51 ]. For instance, Ca 2+ activating ERK1/2 causes pathway activation of osteoblastic-related bone formation [ 52 ].…”