Carboxymethyl chitosan alginate as an enhancer of bone cement repair activity

Critical bone defects often require the use of bone grafts or artificial bone substitutes such as calcium phosphate cement (CPC) or magnesium phosphate cement (MPC). In the study presented here, MPC is modified with CMC and sodium alginate to form a novel bone cement and its properties are investigated in vivo and in vitro.

CARBOXYL METHYL CHITOSAN ALGINATE ENHANCES THE BONE REPAIR EFFECT OF MAGNESIUM PHOSPHATE BONE CEMENT BY ACTIVATING THE FAK-WNT PATHWAY

Ling Yu, Tian Gao, Wei Li, Jian Yang, Yinchu Liu, Yanan Zhao, Ping He, Xuefeng Li, Weichun Guo, Zhengfu Fan, Honglian Dai, Carboxymethyl chitosan-alginate enhances bone repair effects of magnesium phosphate bone cement by activating the FAK-Wnt pathway, Bioactive Materials, Volume 20, 2023, Pages 598-609, ISSN 2452-199X, https://doi.org/10.1016/j.bioactmat.2022.06.017.

Bone defects have a variety of causes, such as injuries, tumors or infections. If bone defects exceed a certain size, self-repair is impossible. Standard solutions in medicine are autologous and allogeneic bone transplants. However, since there is an increased risk of complications during bone removal, disease transmission or even rejection of the implant, the trend is toward artificial bone substitutes such as calcium phosphate cement (CPC). CPC is commonly used for bone reconstruction, but has the disadvantage of low strength, long clotting time and slower absorption.

Magnesium is part of healthy bone structure and makes up about 60% of bone. For this reason, magnesium phosphate cement (MPC) has come into the focus of researchers as an alternative to CPC. Compared to CPC, MPC has high mechanical strength and good biodegradability. In addition, in vivo and in vitro studies confirmed very good biocompatibility and good properties as an inorganic bone filler.

To further improve the osteo-inductive and mechanical properties of MPC, MPC was coupled with carboxylmethylchitosan (CMC) and sodium alginate (SA) in the presented studies. CMC is a water-soluble, positively charged chitosan derivative that can form strong electrostatic interactions with the negatively charged SA. In addition, CMC is structurally similar to glucosamioglycans in the extracellular matrix, which may promote bone formation. The CMC/SA-coupled MPC was evaluated for its biocompatibility and cell adhesion, proliferation, and differentiation properties in this study. In addition, in vivo osteogenicity was estimated using a rat calvarial defect model.

RESULTS

• Highest mechanical strength with addition of 2 % CMC/SA with 59.43 ± 8.81 MPa
• Extension of drying time from 3.40 ± 0.66 min (MPC) to 12.83 ± 1.63 % after addition of 4 % CMC/SA
• Extended possible injection time and reduced maximum temperature after addition of 4 % CMC/SA
• Improved surface structure of MPC by addition of CMC/SA
• In vitro studies with MC3T3-E1 cells showed that in the presence of CMC/SA there was a formation of more pseudopodia, a fibrous structure and an increase in cell proliferation
• No evidence of cytotoxicity
• Compared to MPC, promotion of the expression of osteogenic proteins by CMC/SA.
• MPC-CMC/SA activated the integrin signaling pathway, resulting in increased intracellular FAK phosphorylation
• In vivo: faster biodegradation and formation of thicker, more continuous new bone fragments with MPC-CMC/SA compared with pure MPC
• No evidence of inflammation, necrosis, and infection at the implant site for MPC and MPC-CMC/SA

Conclusions: Overall, a novel bone cement composed of MPC coupled with CMC and SA was developed in the present study. By improving the chemical properties such as mechanical strength, reduced heat generation, and prolonged drying time, MPC-CMC/SA showed good properties for clinical application. In vitro, osteogenic differentiation of MC3T3-E1 cells was detected through the integrin-FAK-Wnt pathway. Moreover, in vivo, new bone formation improved by coupling with CMC-SA. Overall, MPC-CMC/SA shows excellent potential for bone tissue repair and regeneration.

Link to article: Carboxymethyl chitosan-alginate enhances bone repair effects of magnesium phosphate bone cement by activating the FAK-Wnt pathway - ScienceDirect