Abstract
Compared to other materials such as 45S5 bioactive glass (BG), β-tricalcium phosphate (β-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of β-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of β-TCP/45S5-BG composite bone substitute materials.
Highlights
With more than 2 million procedures annually in the United States alone, bone defect augmentation belongs to the most relevant procedures in modern orthopedic surgery in the Western world [1,2]
Β-tricalcium phosphates (TCPs) suffer from two major problems: (i) the material itself stimulates osteogenic differentiation of precursor cells and/or angiogenesis only to a very limited extent compared to other materials, such as bioactive glasses (BGs) [2,7,10,11]; (ii) β-tricalcium phosphate (β-TCP)-based implants in bone suffer from fast degradation and resorption, leading to insufficient “filling” of the treated bone defect and an imbalance between resorption and osseous regeneration, ending in improper consolidation [2,7,12,13]
This study provides a detailed analysis of the impact of BG particles on osteoid formation, scaffold resorption, and angiogenesis in a clinically used bone substitute material
Summary
With more than 2 million procedures annually in the United States alone, bone defect augmentation belongs to the most relevant procedures in modern orthopedic surgery in the Western world [1,2]. The therapy of choice, i.e., defect augmentation using autologous bone, can lead to donor site complications and the available grafting material might not be sufficient to treat large skeletal defects [3,4,5]. Synthetic bone substitutes have been developed that aim to either reduce or even replace the application of autologous bone as a grafting material [2,6]. The most commonly used bone substitute materials to date are calcium phosphates (CaPs), mostly tricalcium phosphates (TCPs; Ca3(PO4)2) that exist in different configurations; of these, the β-TCP configuration is the most popular one for use in orthopedic applications [2,3,7,8,9]. Β-TCPs suffer from two major problems: (i) the material itself stimulates osteogenic differentiation of precursor cells and/or angiogenesis only to a very limited extent compared to other materials, such as bioactive glasses (BGs) [2,7,10,11]; (ii) β-TCP-based implants in bone suffer from (too) fast degradation and resorption, leading to insufficient “filling” of the treated bone defect and an imbalance between resorption and osseous regeneration, ending in improper consolidation [2,7,12,13]
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