Abstract

Biomaterials containing components similar to the native biological tissue would have benefits as an implantable scaffold material. To obtain such biomimetic materials, cells may be great contributors because of their crucial roles in synthetic organics. In addition, the synthesized organics—especially those derived from osteogenic differentiated cells—become a place where mineral crystals nucleate and grow even in vitro. Therefore, to fabricate an organic/inorganic composite material, which is similar to the biological osteoid tissue, bone marrow derived mesenchymal stem cells (BMSCs) were cultured in a 3D fibrin gel in this study. BMSCs secreted bone-related proteins that enhanced the biomineralization within the gel when the cells were cultured with an osteogenic differentiation medium. The compositions of both synthesized matrices and precipitated minerals in the obtained materials altered depending on the cell culture period. The mineral obtained in the 3D gel showed low crystalline hydroxyapatite. The composite materials also showed excellent osteoconductivity with new bone formation when implanted in mice tibiae. Thus, we demonstrated the contributions of cells for fabricating implantable organic/inorganic composite gel materials and a method for controlling the material composition in the gel. This cell-based material fabrication method would be a novel method to fabricate organic/inorganic composite biomimetic materials for bone tissue engineering.

Highlights

  • Bone tissue has critical roles in supporting body weight, enabling motility, and protecting important organs [1,2]

  • We hypothesized that culturing bone marrow derived mesenchymal stem cells (BMSCs) in 3D fibrin gel would form organic/inorganic composite materials containing cells, bone matrix proteins, and minerals that are similar to biological osteoid tissue

  • BMSCs were cultured in 3D fibrin gel with osteogenic differentiation medium

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Summary

Introduction

Bone tissue has critical roles in supporting body weight, enabling motility, and protecting important organs [1,2]. For bone defects caused by regional segmentation for tumor extractions, necrosis due to X-ray radiation, or injury [4,5], the bones are reconstructed using biomaterials, including titanium or sintered ceramic materials, to recover the bone functions [6,7] This bone reconstruction supports body motility and rebuilds the morphology of the original tissue. On the other hand, integrating implanted biomaterials with host hard tissues is considered a challenging issue in bone tissue engineering [13] For this integration, fabrication of implantable materials that contain both organics and minerals similar to the components of biological osteoid tissue might be effective, because naturally derived organics generally have higher affinity to host cell and tissue. We hypothesized that culturing BMSCs in 3D fibrin gel would form organic/inorganic composite materials containing cells, bone matrix proteins, and minerals that are similar to biological osteoid tissue. The chemical properties of the obtained 3D constructs were investigated in this study

BMSCs Culture in 3D Fibrin Gel
Deposition and Distribution of Matrix and Minerals in Fibrin Gel
Composition of Obtained 3D Constructs
Osteoconductivity of Synthesized Materials
BMSCs Culture in Fibrin Gel
Image Analysis
Statistical Analysis
Conclusions

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