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Background <p>Osteochondral defects remain a major clinical challenge due to the limited intrinsic healing capacity of articular cartilage and the complex structural integration required between cartilage and subchondral bone. Tissue-engineered scaffolds offer a promising strategy for improving repair outcomes.</p> Methods <p>We developed a 3D bioprinted bilayer GelMA/hydroxyapatite (HAp) hydrogel scaffold incorporating miR-140-5p–modified mesenchymal stem cells (MSCs). The upper chondral-oriented layer consisted of 5% GelMA60, while the lower relatively stiffer HAp-containing layer comprised 5% GelMA90 with 1% HAp. Mechanical properties, cell viability, migration, and differentiation were evaluated in vitro. Osteochondral repair efficacy was further assessed in a rabbit femoral condyle defect model using macroscopic scoring, Micro-CT, and histological analysis.</p> Results <p>The bilayer scaffold demonstrated enhanced compressive strength and maintained favorable swelling characteristics. MSC viability remained high in both scaffold groups and exceeded 90% by day 5 after bioprinting. miR-140-5p modification significantly promoted MSC migration and upregulated chondrogenic markers. In vivo, the functionalized scaffold markedly improved cartilage surface integrity, subchondral bone reconstruction, and ICRS scores compared with controls.</p> Conclusion <p>The 3D bioprinted bilayer GelMA/HAp scaffold combined with miR-140-5p–modified MSCs significantly enhances osteochondral repair in a rabbit model and represents a promising strategy for clinical translation.</p>

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3D bioprinted bilayer GelMA/HAp hydrogel scaffold functionalized with miR-140-5p–modified MSCs for enhanced osteochondral regeneration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Yingjie Xu,
  • Junhui Xing,
  • Ziyu Zhang,
  • Minghui Li,
  • Jing Qu,
  • Hongtao Zhang

摘要

Background

Osteochondral defects remain a major clinical challenge due to the limited intrinsic healing capacity of articular cartilage and the complex structural integration required between cartilage and subchondral bone. Tissue-engineered scaffolds offer a promising strategy for improving repair outcomes.

Methods

We developed a 3D bioprinted bilayer GelMA/hydroxyapatite (HAp) hydrogel scaffold incorporating miR-140-5p–modified mesenchymal stem cells (MSCs). The upper chondral-oriented layer consisted of 5% GelMA60, while the lower relatively stiffer HAp-containing layer comprised 5% GelMA90 with 1% HAp. Mechanical properties, cell viability, migration, and differentiation were evaluated in vitro. Osteochondral repair efficacy was further assessed in a rabbit femoral condyle defect model using macroscopic scoring, Micro-CT, and histological analysis.

Results

The bilayer scaffold demonstrated enhanced compressive strength and maintained favorable swelling characteristics. MSC viability remained high in both scaffold groups and exceeded 90% by day 5 after bioprinting. miR-140-5p modification significantly promoted MSC migration and upregulated chondrogenic markers. In vivo, the functionalized scaffold markedly improved cartilage surface integrity, subchondral bone reconstruction, and ICRS scores compared with controls.

Conclusion

The 3D bioprinted bilayer GelMA/HAp scaffold combined with miR-140-5p–modified MSCs significantly enhances osteochondral repair in a rabbit model and represents a promising strategy for clinical translation.