Fish-derived biomaterials in bone tissue engineering: molecular mechanisms and scaffold innovations for enhanced regeneration

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Abstract
Bone tissue engineering (BTE) requires biomaterials that can replicate the extracellular matrix while supporting osteogenesis and angiogenesis. Collagen, especially type I, is central to BTE. Fish-derived collagen (FC) and hydroxyapatite (HAp) provide sustainable and biocompatible alternatives to mammalian sources, offering comparable structural and biological properties with reduced immunogenic risk. This review highlights recent progress, emphasizing quantitative benchmarks and mechanistic insights that distinguish fish-derived biomaterials from conventional counterparts. A systematic analysis of studies on fish collagen-based scaffolds, fish-derived bioceramics, coatings, and decellularized fish scales was conducted. Data on mechanical properties (compressive strength, elastic modulus), porosity, degradation profiles, and biological outcomes (osteogenesis, angiogenesis, immunomodulation) were compared with existing mammalian-derived scaffolds. FC-based scaffolds demonstrated compressive strength of 2–5 MPa, elastic modulus of 50–150 MPa, and porosity of 60–90%, values within cancellous bone ranges. Degradation rates of 4–12 weeks aligned with bone remodeling. Decellularized fish scales exhibited superior stiffness (50–120 MPa) and hierarchical collagen–apatite architecture, supporting cell adhesion and VEGF-mediated angiogenesis. Fish bone–derived bioceramics showed controlled ion release, enhancing RUNX2 and BMP-2 expression. Compared to mammalian collagen, FC scaffolds exhibited improved osteoconductivity, tunable degradation, and lower immunogenicity. Fish-derived biomaterials provide quantifiable structural and biological advantages over conventional scaffolds, combining biomimetic architecture, osteoinductive signaling, and immunomodulatory effects. While challenges remain in mechanical reinforcement and clinical validation, evidence supports their translational potential, especially in composite and 3D-printed platforms for bone regeneration.
Funding Information
  • Fasa University of Medical Sciences (404056)

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