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

Tianpeng Xu, Yuhe Yang, Di Suo, Ho Pan Bei, Xiaoxiao Xu, Xin Zhao

Research output: Journal article publicationJournal articleAcademic researchpeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Article number2200314
Issue number36
Publication statusPublished - 8 Sept 2022


  • angiogenesis
  • bone regeneration
  • electrosprayed microspheres
  • osteogenesis
  • regeneration-enhancer-element

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)


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