Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copolymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects

Abstract

Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA–HAP and Gel/HA–HAP–SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA–HAP composites showed no systemic toxicity to rats. Gel/HA–HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA–HAP–SDF-1 composites can be a feasible material for use as bone void fillers.

Keywords

• tissue engineering
• biomaterial
• hyaluronate
• mesenchymal stem cells
• hydroxyapatite
• bone regeneration