Modulation of bioactive calcium phosphate micro/nanoparticle size and shape during in situ synthesis of photo-crosslinkable gelatin methacryloyl based nanocomposite hydrogels for 3D bioprinting and tissue engineering

用于 3D 生物打印和组织工程的光交联明胶甲基丙烯酰基纳米复合水凝胶原位合成过程中生物活性磷酸钙微/纳米颗粒尺寸和形状的调节

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作者:Amitava Bhattacharyya, Gopinathan Janarthanan, Taeyang Kim, Shiva Taheri, Jisun Shin, Jihyeon Kim, Hyun Cheol Bae, Hyuk-Soo Han, Insup Noh

Background

The gelatin-methacryloyl (GelMA) polymer suffers shape fidelity and structural stability issues during 3D bioprinting for bone tissue engineering while homogeneous mixing of reinforcing nanoparticles is always under debate. Method: In this study, amorphous calcium phosphates micro/nanoparticles (CNP) incorporated GelMA is synthesized by developing specific sites for gelatin structure-based nucleation and stabilization in a one-pot processing. The process ensures homogenous distribution of CNPs while different concentrations of gelatin control their growth and morphologies. After micro/nanoparticles synthesis in the gelatin matrix, methacrylation is carried out to prepare homogeneously distributed CNP-reinforced gelatin methacryloyl (CNP GelMA) polymer. After synthesis of CNP and CNP GelMA gel, the properties of photo-crosslinked 3D bioprinting scaffolds were compared with those of the conventionally fabricated ones.

Conclusion

For 3D bioprinting using GelMA like photo cross-linkable polymers, where structural stability and homogeneous control of nanoparticles are major concerns, CNP GelMA is beneficial for even bone tissue regeneration within short period.

Results

The shape (spindle to spherical) and size (1.753 μm to 296 nm) of the micro/nanoparticles in the GelMA matrix are modulated by adjusting the gelatin concentrations during the synthesis. UV cross-linked CNP GelMA (using Irgacure 2955) has significantly improved mechanical (three times compressive strength), 3D printability (160 layers, 2 cm self-standing 3D printed height) and biological properties (cell supportiveness with osteogenic differentiation). The photo-crosslinking becomes faster due to better methacrylation, facilitating continuous 3D bioprinting or printing.

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