Abstract

Different types of biomaterials have been used to repair the defect of bony orbit. However, exposure and infections are still critical risks in clinical application. Biomaterials with characteristics of osteogenesis and antibiosis are needed for bone regeneration. In this study, we aimed to characterize the antimicrobial effects of cathelicidin-LL37 and to assess any impacts on osteogenic activity. Furthermore, we attempted to demonstrate the feasibility of LL37 as a potential strategy in the reconstruction of clinical bone defects. Human adipose-derived mesenchyme stem cells (hADSCs) were cultured with different concentrations of LL37 and the optimum concentration for osteogenesis was selected for further in vitro studies. We then evaluated the antibiotic properties of LL37 at the optimum osteogenic concentration. Finally, we estimated the efficiency of a PSeD/hADSCs/LL37 combined scaffold on reconstructing bone defects in the rat calvarial defect model. The osteogenic ability on hADSCs in vitro was shown to be dependent on the concentration of LL37 and reached a peak at 4 μg/ml. The optimum concentration of LL37 showed good antimicrobial properties against Escherichia coli and Staphylococcus anurans. The combination scaffold of PSeD/hADSCs/LL37 showed superior osteogenic properties compared to the PSeD/hADSCs, PSeD, and control groups scaffolds, indicating a strong bone reconstruction effect in the rat calvarial bone defect model. In Conclusion, LL37 was shown to promote osteogenic differentiation in vitro as well as antibacterial properties. The combination of PSeD/hADSCs/LL37 was advantageous in the rat calvarial defect reconstruction model, showing high potential in clinical bone regeneration.

Highlights

  • Bony orbital defects can be a result of trauma, malformations and iatrogenic surgery, and can lead to many functional and cosmetic problems that often require orbit reconstruction

  • In this study, we evaluated the combination of LL37 and Human adipose-derived mesenchyme stem cells (hADSCs) in the treatment of rat calvarial defect model

  • We applied LL37 accompanied with Poly(sebacoyl diglyceride) (PSeD)/hADSCs and showed the ability of bone regeneration without stress stimulation, which is similar to that of the bony orbit. These results suggested that the combination of PSeD/hADSCs/LL37 can significantly accelerate the process of bone reconstruction

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Summary

Introduction

Bony orbital defects can be a result of trauma, malformations and iatrogenic surgery, and can lead to many functional and cosmetic problems that often require orbit reconstruction. Numerous types of biomaterials have been used to reconstruct the orbit including autogenous materials, metallic meshes, porous polyethylene, and resorbable biomaterials Bioresorbable implants are becoming increasingly popular as they have several attractive properties including the ability to be shaped, strong mechanical integrity after resorption, and do not cause complications at the donor sites (Xuan et al, 2020). Grafts in the bony orbital region are vulnerable to exposure and infections. In comparison to solid sheet materials that are be encapsulated, bioresorbable implants are at higher risk of infection and inflammation. Patients are at risk of different complications including exposure, migration, and the formation of fistulae and cysts

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