Scaffolds are crucial in cell proliferation particularly, the desired cells. They are very important, especially in tissue engineering because they preserve tissue volume, provide temporary mechanical functions and also deliver bio factors. An effective scaffold must hence, balance the mechanical function with biological properties, including the delivery of bio factors. Previously, the mechanical function of the scaffolds has been enhanced by various cross-linking methods and compositions whereas bio factor delivery has been improved by the changing of both physical and chemical junction methods. In the chitosan/tripolyphosphate backbone, the primary amine plays a very crucial role in the biomedical applications and the chitosan-based porous scaffolds have been used extensively in tissue engineering. However, the regulation of uncross-linking the primary amine content in scaffolds so as to achieve particular biological and mechanical properties has remained a challenge.

Recently, a group of scientists led by Professor Xuehui Zhang at Peking university successfully fabricated chitosan scaffolds and investigated the effects of the composition and properties of the scaffold under various conditions. The research team studied the mechanism of the scaffolds in the absorption and release of proteins, in order to understand the role of uncross-linking primary amine on the pH-responsive delivery of bioactive factors. The new research is now published in Materials Science & Engineering C.

Briefly, the researchers prepared the chitosan scaffolds with controlled primary amine content based on the ionic-dependent solubility of tripolyphosphate/chitosan and the freezing process, then they studied the effects of concentration of chitosan and NaCl in the crosslinking solution on the primary amine content using infrared spectroscopy, ninhydrin assays and elemental analysis. The elemental analysis was used to study the morphology and elemental composition of the scaffolds. The swelling behavior of the scaffold was then studied using a digital camera and an electronic balance. In addition, cytotoxicity assays were carried out. BSA assays were also carried out in order to study the BSA adsorption, release and concentration. They also studied the effect of the primary amine content on the behavior of cells in rat bone marrow mesenchymal stem cells by studying the adhesion of the mesenchymal cells using confocal microscopy.

The authors observed that the primary amine content decreased with increasing concentration of tripolyphosphate and decreasing the concentration of NaCl. The physicochemical properties such as the swelling behavior and the mechanical strength of chitosan scaffolds were affected by the primary amine content in the scaffolds. They also noted that the uncross-linking primary amine in the scaffolds affected the protein adsorption and protein release. They observed that the number of rat bone marrow mesenchymal cells increased with their increasing NaCl concentration or decreasing tripolyphospate concentration.

In conclusion, the research carried out by Peking university scientists demonstrated that uncross-linking primary amine in scaffolds affects mechanical properties, cell behavior and protein adsorption hence it can be used for chemical and biological modifications in the biomedical field. The results of the research show that porous tripolyphosphate/chitosan that contain uncross-linking primary amines have the potential to be used in the applications in bone regenerative therapies. In addition, the study acts as a basis for future research in modification and application of scaffolds, pH-responsive adsorption and protein or drug release from scaffolds in medicine.

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Yongxiang Xu, Jianmin Han, Yuan Chai, Shenpo Yuan, Hong Lin, Xuehui Zhang, Development of porous chitosan/tripolyphosphate scaffolds with tunable uncross-linking primary amine content for bone tissue engineering: Materials Science & Engineering C 85 (2018), page 182–190.