Copper Ion-Modified Germanium Phosphorus Nanosheets Integrated with an Electroactive and Biodegradable Hydrogel for Neuro-Vascularized Bone Regeneration

Adv Healthc Mater. 2023 Oct;12(27):e2301151. doi: 10.1002/adhm.202301151. Epub 2023 Jul 8.

Abstract

Severe bone defects accompanied by vascular and peripheral nerve injuries represent a huge orthopedic challenge and are often accompanied by the risk of infection. Thus, biomaterials with antibacterial and neurovascular regeneration properties are highly desirable. Here, a newly designed biohybrid biodegradable hydrogel (GelMA) containing copper ion-modified germanium-phosphorus (GeP) nanosheets, which act as neuro-vascular regeneration and antibacterial agents, is designed. The copper ion modification process serves to improve the stability of the GeP nanosheets and offers a platform for the sustained release of bioactive ions. Study findings show that GelMA/GeP@Cu has effective antibacterial properties. The integrated hydrogel can significantly boost the osteogenic differentiation of bone marrow mesenchymal stem cells, facilitate angiogenesis in human umbilical vein endothelial cells, and up-regulate neural differentiation-related proteins in neural stem cells in vitro. In vivo, in the rat calvarial bone defect mode, the GelMA/GeP@Cu hydrogel is found to enhance angiogenesis and neurogenesis, eventually contributing to bone regeneration. These findings indicate that in the field of bone tissue engineering, GelMA/GeP@Cu can serve as a valuable biomaterial for neuro-vascularized bone regeneration and infection prevention.

Keywords: angiogenesis; bone regeneration; copper; hydrogels; innervation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Biocompatible Materials / pharmacology
  • Bone Regeneration
  • Copper / pharmacology
  • Germanium* / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels / pharmacology
  • Osteogenesis*
  • Phosphorus / pharmacology
  • Rats

Substances

  • Hydrogels
  • Copper
  • Germanium
  • Phosphorus
  • Biocompatible Materials
  • Anti-Bacterial Agents