Nano Biomedicine
ORIGINAL ARTICLE

Application of TNT-containing Collagen Gel as Bone Substitute Materials

Harumitsu TSUBOUCHI1, Satoshi KOMASA2, Akiko MIYAKE3, Yoshiro TAHARA4, Tomonari TANAKA5, Tohru SEKINO6, and Kenji MAEKAWA1


1Department of Removable Prosthodontics and Occlusion, School of Dentistry,
2Department of Oral Health Sciences, Faculty of Health Sciences,
3Department of Oral Health Engineering, Faculty of Health Sciences,
Osaka Dental University, Osaka, Japan
4Department of Chemical Engineering and Materials Science,
Doshisha University, Kyoto, Japan
5Department of Biobased Materials Science, Graduate School of Science and Technology,
Kyoto Institute of Technology, Kyoto, Japan
6Department of Advanced Hard Materials, SANKEN,
The University of Osaka, Osaka, Japan



Nano Biomed 2025; 17(2): 73-84, (Dec 30, Nano Biomedicine)

Synopsis
This study investigated the potential of titanium nanotube (TNT)-containing collagen gels as novel bone graft materials for enhancing hard tissue differentiation in extensive bone defects. TNT was synthesized via low-temperature chemical methods and incorporated into a collagen gel modified with glycerol and pullulan. Characterization of the TNT-containing collagen gel confirmed the formation of nanoscale tubular structures and the presence of titanium. In vitro analysis of rat bone marrow cells (RBMCs) cultured with the TNT-containing collagen gel showed significantly higher cell adhesion, alkaline phosphatase (ALP) activity, and calcium deposition compared to the control and collagen gel groups. In vivo evaluation using a rat cranial defect model revealed increased bone volume and trabecular density in the TNT-containing collagen gel group, with histological observations indicating advanced calcified hard tissue formation. These findings suggest that the nanotubular structure of TNT promotes extracellular matrix formation and osteoblast activity, supporting bone regeneration. Although further investigation is needed to optimize TNT concentration and assess long-term effects, TNT-containing collagen gels demonstrate promise as next-generation bone graft materials for repairing extensive bone defects. The combination of TNT with glycerol- and pullulan-blended collagen gels may create a synergistic effect, enhancing both the mechanical and bioactive properties of the composite material for advanced bone tissue engineering applications.

Key words titanium nanotube, collagen gel, bone graft materials, bone regeneration, hard tissue differentiation

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DOI: 10.11344/nano.17.73

Tsubouchi H, Komasa S, Miyake A, Tahara Y, Tanaka T, Sekino T, Maekawa K. Application of TNT-containing collagen gel as bone substitute materials. Nano Biomed 2025; 17: 73-84