Abstract

The use of bone graft materials is required for the treatment of bone defects damaged beyond the critical defect; therefore, injectable calcium phosphate cement (CPC) is actively used after surgery. The application of various polymers to improve injectability, mechanical strength, and biological function of injection-type CPC is encouraged. We previously developed a chitosan–PEG conjugate (CS/PEG) by a sulfur (VI) fluoride exchange reaction, and the resulting chitosan derivative showed high solubility at a neutral pH. We have demonstrated the CPC incorporated with a poly (ethylene glycol) (PEG)-grafted chitosan (CS/PEG) and developed CS/PEG CPC. The characterization of CS/PEG CPC was conducted using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The initial properties of CS/PEG CPCs, such as the pH, porosity, mechanical strength, zeta potential, and in vitro biocompatibility using the WST-1 assay, were also investigated. Moreover, osteocompatibility of CS/PEG CPCs was carried out via Alizarin Red S staining, immunocytochemistry, and Western blot analysis. CS/PEG CPC has enhanced mechanical strength compared to CPC, and the cohesion test also demonstrated in vivo stability. Furthermore, we determined whether CS/PEG CPC is a suitable candidate for promoting the osteogenic ability of Dental Pulp Stem Cells (DPSC). The elution of CS/PEG CPC entraps more calcium ion than CPC, as confirmed through the zeta potential test. Accordingly, the ion trapping effect of CS/PEG is considered to have played a role in promoting osteogenic differentiation of DPSCs. The results strongly suggested that CS/PEG could be used as suitable additives for improving osteogenic induction of bone substitute materials.

Highlights

  • Musculoskeletal disorders, such as osteoporosis, are chronic conditions that indicate the deterioration of bone tissue and loss of strength

  • We previously developed a chitosan derivative, soluble at a neutral pH, which was synthesized from coupling chitosan–ESF (CS/ESF) and mPEG–NH2 to form a chitosan– PEG conjugate (CS/PEG), grafting chitosan with PEG–NH2 by a sulfur (VI) fluoride exchange (SuFEx) reaction, as reported by Sharpless et al [21]

  • The present study further investigated the application of CS/PEG in calcium phosphate cement (CPC) to enhance the osteogenic differentiation of human dental pulp stem cells (DPSCs)

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Summary

Introduction

Musculoskeletal disorders, such as osteoporosis, are chronic conditions that indicate the deterioration of bone tissue and loss of strength. Over two million bone grafting surgical procedures are performed worldwide; osteoporotic fractures are major clinical challenges [1]. Bone grafting is used to repair and regenerate bones through the transplantation of bone tissue materials [2]. Bone defect treatment is generally performed using autologous and allogeneic bone grafting. Clinical results for the complete regeneration of bone tissue are not readily available. Limited donor supply and the morbidity of donor sites are typical drawbacks of autologous bone grafting. Allogeneic bone grafting transplantation carries a risk of immune rejection and potential disease transmission, resulting in serious harm to the patient’s health

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