Three-dimensional printing technologies exhibit tremendous potential in the advancing fields of tissue engineering and regenerative medicine due to the precise spatial control over depositing the biomaterial. Despite their widespread utilization and numerous advantages, the development of suitable novel biomaterials for extrusion-based 3D printing of scaffolds that support cell attachment, proliferation, and vascularization remains a challenge. Multi-material composite hydrogels present incredible potential in this field. Thus, in this work, a multi-material composite hydrogel with a promising formulation of chitosan/gelatin functionalized with egg white was developed, which provides good printability and shape fidelity. In addition, a series of comparative analyses of different crosslinking agents and processes based on tripolyphosphate (TPP), genipin (GP), and glutaraldehyde (GTA) were investigated and compared to select the ideal crosslinking strategy to enhance the physicochemical and biological properties of the fabricated scaffolds. All of the results indicate that the composite hydrogel and the resulting scaffolds utilizing TPP crosslinking have great potential in tissue engineering, especially for supporting neo-vessel growth into the scaffold and promoting angiogenesis within engineered tissues.
Graphic abstract
In recent years, 3D bioprinting has attracted broad research interest in biomedical engineering and clinical applications. However, there are two issues need to be solved urgently at present, the development of ink is the first pressing thing for 3D printing tissue engineering scaffold, other thing is the promotion of angiogenesis in the scaffold. Therefore, a gelatin/sodium alginate‐based hydrogel with protein‐rich is developed here, which is prepared by gelatin, sodium alginate, and soy protein/soy peptide powder. The prepared inks exhibit excellent shear‐thinning behavior, which contribute to extrusion‐based printing; also shown good crosslinking ability by calcium chloride. The macroporous composite scaffolds are printed by 3D printing using the developed ink and the physicochemical properties of the scaffolds are evaluated. Moreover, the cytocompatibility of printed scaffold is characterized by using human umbilical vein epidermal cells, results show that the scaffolds with soy protein and soy peptide powder can promote cell attach, spread, migration, and proliferation. The further research of chicken embryo allantoic membrane assay and animal experiment are carried, and results present that the scaffold can promote the growth of neo‐vessels in the scaffold, which means the developed ink with soy protein and soy peptide powder has great potential for angiogenesis.
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