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Bioactivity-Structure Synergy for Osteogenesis: An Alpha-Ketoglutarate-Releasing PA66/HAp/Gelatin Gradient Porous

Siluo Dai1, Jiaxin Hu1, Yiran Li1

  • 1Analytical & Testing Center, Sichuan University, Chengdu 610064, P. R. China.

ACS Biomaterials Science & Engineering
|April 1, 2026
PubMed
Summary

This study introduces a novel 3D-printed scaffold using gelatin and alpha-ketoglutarate (AKG) to improve bone regeneration. The enhanced scaffold promotes dense cell attachment and significantly increases new bone formation in vivo.

Keywords:
3D-printed scaffoldcell adhesiongelatin networkα-ketoglutarate

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • 3D-printed porous scaffolds are crucial for bone repair but often suffer from poor cell attachment due to large pore sizes.
  • This limitation results in low-density, uneven cell distribution, hindering effective bone regeneration.

Purpose of the Study:

  • To develop a gradient-functionalized scaffold that enhances initial cell adhesion and promotes osteogenic differentiation for improved bone repair.
  • To address the limitations of conventional 3D-printed scaffolds by incorporating a bioactive network.

Main Methods:

  • A 3D-printed polyamide 66/hydroxyapatite (PH) composite scaffold was functionalized with an alpha-ketoglutarate (AKG)-loaded gelatin (Gel/AKG) network.
  • Material optimization identified a 5 wt % gelatin with 0.25 wt % AKG formulation for optimal scaffold properties.
  • The scaffold's ability to guide cell colonization, facilitate bone ingrowth, and enhance osteogenic activity was evaluated.

Main Results:

  • The Gel/AKG network created an integrated microporous structure, significantly improving surface properties for dense early cell colonization.
  • Gelatin degradation provided space for bone ingrowth, while sustained AKG release promoted cell osteogenic activity.
  • In vivo studies showed an 110% increase in new bone volume in the experimental group compared to controls after 8 weeks.

Conclusions:

  • The developed gradient-functionalized scaffold successfully integrates mechanical support with guided cell adhesion and bioactive regulation.
  • This spatiotemporally coordinated system offers a promising solution for bone defect repair by enhancing structural compatibility and functional regeneration.