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Background: The treatment of bone defects, in maxillofacial surgery and orthopedics, represents a major public health challenge. Autologous graft remains the "gold standard" treatment, but the availability of grafts is limited. Bioactive materials, such as silicate-based bioactive glass (Bioglass®), are among the bone substitutes the most widely used as alternatives, for their osteogenic potential but their resorption is limited. New glass compositions containing mainly pyrophosphate and orthophosphate entities have been elaborated by soft chemistry [1]. Their biological interest is linked to the control of the resorption rate (through the orthophosphate/pyrophosphate ratio) by biochemical hydrolysis. The present study aimed to investigate the osteoformation potential, the resorption rate and the impact on the early bone healing process of a pyrophosphate-based glass with a ratio orthophosphate/ pyrophosphate =3 (NaPYG_030), using a critical-size model in rat calvaria.
Methodology: Circular 8 mm-diameter bone defects were created on calvaria of 12 weeks-old male Winstar rats. They were left empty, or filled either with a composition of pyrophosphate-based glasses, NaPYG_030 (Ca2 +)1,57 (Na+)0,14 (H+)0,05 (PO4 3 -)0,67(P2 O7 4-)0,33] (H2O)10,36 (n=6) or with silicate-based bioactive glass Bioglass® (n=6), used as control. The radiopacity was evaluated in vivo, using micro-CT analyses, performed immediately after surgery and on days, 15, 30, and 60. Histological analyses were performed after animal sacrifice at 30 and 60 days post-surgery. Tissue response, bone formation, and material resorption were assessed using non-decalcified histology. The expression levels of selected inflammation-, angiogenesis-, and bone-related genes, in the defect’s tissue were determined using RT-PCR after animal sacrifice at 7 and 14 days post-surgery.
Results: In vivo follow-up of the defect’s radiopacity volume (evidence for the residual implanted material and the newly formed bone volume) showed differences related to the bone substitute used. Compared to the Bioglass®-filled defects, the NaPYG_030 group exhibited a significant (p < 0.05) decrease[1] in radiopacity at all time points tested. Moreover, the study of the transcriptional profile of the genes showed that in the presence of NaPYG_030 the expression of TNFα, IL-6, and IL-8, ANG, PECAM and VWF as well as that of ALP, BGLAP, SP7 and Col1A1 was significantly decreased on the day 14 post-surgery. On day 30 and 60 post-surgery, the histological analysis showed an absence of inflammation and/or foreign body reaction and newly-formed bone around the particles of both implanted materials. However, while the mineralized tissue was in close contact with the Bioglass® particles, a thin layer of unmineralized tissue was observed at the interphase NaPYG_030-newly formed bone, suggesting an ongoing resorption process.
Conclusions: In conclusion, the results obtained in the present study indicated the biological performance of new pyrophosphate-based glass in critical-size defects. The NaPyG-30 influenced the early critical events involved in bone regeneration by modulating specifically the expression of genes pertinent to inflammation, angiogenesis and osteogenesis, and exhibited both, efficient bone-forming capacity and resorbability making it an attractive bone substitute option to repair defects in the maxillofacial area.
[[1]] Mayen, L. et al., Acta Biomater.103,333-345 (2020).
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