Porous scaffolds with mechanical-biological properties balance for bone tissue engineering


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.

Porous scaffolds with mechanical-biological properties balance for bone tissue engineering - Medicine Innovates

About the author

Eya Wolfson, A PhD student in the Direct PhD Track Program at Tel-Aviv University. She has received her BSc from the Research focused Honors’ Biology program in the Faculty of Life Sciences in Tel Aviv University in 2013, and started her PhD in Prof. Pinkas-Kramarski’s lab later that year. During her time in the lab she has been a part of several cancer research projects, and was involved in study of cancer physiology, signaling pathways and autophagy, as well as in examination and development of personalized anti-cancer therapeutics. Mrs. Wolfson’s current research focuses on the role of nucleolin in ErbB2 ligand-independent signaling in ErbB2-positive tumors. An interaction that was found to be associated with poor prognosis and increased disease progression in ErbB2-positive breast cancer patients as part of this study. This study involves the examination of the physiological roles and oncogenic significance of this interaction, as well as the identification of novel therapeutic targets and the development of personalized treatment strategies, based on these targets.

About the author

Prof. Ronit Pinkas-Kramarski , Head of the Neurobiology Department at the Faculty of Life Sciences, Tel Aviv University, Director of the Prajs–Drimmer Institute for the Development of Anti–Degenerative Drugs, Tel-Aviv University.

Prof. Pinkas-Kramarski has a longtime experience in cell biology research, particularly regarding cell signaling pathways and metabolic processes. Prof. Pinkas-Kramarski did her PhD studies in biochemistry at Tel-Aviv University. She has completed her Post-Doctoral studies at the Weizmann Institute of science in Israel, in the field of molecular cell biology, specifically studying the combinatorial signaling of the ErbB family of receptor tyrosine kinases. Upon completion of her Post-Doctoral studies, Prof. Pinkas-Kramarski received a position at the Neurobiology Dep. in Tel Aviv University, and in 2016 was appointed as a full-Professor.

The Pinkas-Kramarski lab, active since 1997, mainly focuses on studying pathways that regulate cell proliferation and viability. Her laboratory study signaling mediated by the ErbB family of receptor tyrosine kinases. Her research lead to identification of new oncogenic interaction between ErbB receptors and nucleolin leading to enhanced tumor cell growth. Her studies demonstrated that nucleolin could activate the receptor in a ligand-independent manner. Other research projects performed in the lab include the study of autophagy at the molecular level by exploring the role of Beclin 1 protein, and at the physiological level in cancer and neurodegeneration. In addition, the Pinkas-Kramarski lab specializes in exploration of novel treatment strategies as part of the personalized medicine approach, namely development of specific-target drugs, and the design and testing of efficient drug combinations.


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.

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