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Related Experiment Video

Updated: Mar 1, 2026

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Developing tissue-engineered bone with pre-vascularization and innervation using a bottom-up approach involving

Guoding Cao1, Yaoye Zhao1, Haoqiang Zhang2

  • 1Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, People's Republic of China.

Biofabrication
|February 27, 2026
PubMed
Summary

This study developed a novel vascular-nerve-tissue-engineered bone (TEB) using a bottom-up approach. The engineered bone integrates blood vessel and nerve regeneration for enhanced bone repair.

Keywords:
building blocksinnervated tissue-engineered bonemicrotissueneurovascularized tissue-engineered bonevascularized tissue-engineered bone

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Bone regeneration requires coordinated blood vessel (angiogenesis) and nerve (neurogenesis) development.
  • Current tissue-engineered bone (TEB) strategies often struggle to integrate vascular and neural components effectively.
  • A bottom-up approach using modular microtissues offers a novel strategy for TEB construction.

Purpose of the Study:

  • To develop a novel vascular-nerve-tissue-engineered bone (TEB) using a bottom-up modular microtissue approach.
  • To investigate the feasibility of constructing TEB by encapsulating vascular-neural-bone microtissues within gelatin methacrylate (GelMA) hydrogels.
  • To evaluate the concurrent capabilities of angiogenesis, neurogenesis, and osteogenesis in the developed TEB for bone repair.

Main Methods:

  • Generated vascular-nerve-bone microtissues via 3D co-culture of bone marrow mesenchymal stem cells (BMSCs), endothelial progenitor cells (EPCs), and Schwann cells (SCs).
  • Encapsulated these microtissues as modular units within GelMA hydrogels to create large-scale vascular-neural TEB.
  • Assessed the construct's functionality at molecular, cellular, and tissue/organ levels, focusing on regenerative capacities.

Main Results:

  • Successfully constructed vascular-neural TEB using a microtissue-based, bottom-up approach.
  • Demonstrated the feasibility of the protocol at multiple biological levels.
  • The GelMA/MSC/EPC/SC TEB exhibited concurrent angiogenesis, neurogenesis, and osteogenesis capabilities.

Conclusions:

  • The microtissue-based modular construction is a feasible strategy for creating multifunctional TEB.
  • The developed TEB shows promise for simultaneous blood vessel and nerve regeneration alongside bone formation.
  • This approach offers novel insights for designing advanced bone grafts for clinical applications in bone defect treatment.