Size effect of fish gelatin nanoparticles on the mechanical properties of collagen film based on its hierarchical structure

Successful regeneration of large segmental bone defects remains a major challenge in clinical orthopedics, thus it is of important significance to fabricate a suitable alternative material to stimulate bone regeneration. Due to their excellent biocompatibility, sufficient mechanical strength, and similar structure and composition of natural bone, the mineralized collagen scaffolds (MCSs) have been increasingly used as bone substitutes via tissue engineering approaches. Herein, we thoroughly summarize the state of the art of MCSs as tissue-engineered scaffolds for acceleration of bone repair, including their fabrication methods, critical factors for osteogenesis regulation, current opportunities and challenges in the future. First, the current fabrication methods for MCSs, mainly including direct mineral composite, in-situ mineralization and 3D printing techniques, have been proposed to improve their biomimetic physical structures in this review. Meanwhile, three aspects of physical (mechanics and morphology), biological (cells and growth factors) and chemical (composition and cross-linking) cues are described as the critical factors for regulating the osteogenic feature of MCSs. Finally, the opportunities and challenges associated with MCSs as bone tissue-engineered scaffolds are also discussed to point out the future directions for building the next generation of MCSs that should be endowed with satisfactorily mimetic structures and appropriately biological characters for bone regeneration.

FT-IR, in combination with residual amino group determination using a fluorescence technique, has been used to investigate the chemical functional groups involved in the cross-linking reaction between glutaraldehyde and gelatin molecules. The results suggest that, at high pH values (i.e., close to the pK(a) of lysine), the cross-linking reaction is mainly governed by the well-known Schiff base formation, whereas at low pH (i.e., when the amino groups of lysine are protonated), the reaction may also involve the -OH groups of hydroxyproline and hydroxylysine, leading to the formation of hemiacetals.