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Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex
Christin Neuber1, Luisa Niedenzu2, Sabine Schulze2
1Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany.
Abstract:
The inducible enzyme cyclooxygenase-2 (COX-2) and the subsequent synthesis of eicosanoids initiated by this enzyme are important molecular players in bone healing. In this pilot study, the suitability of a novel selective COX-2 inhibitor bearing a nitric oxide (NO)-releasing moiety was investigated as a modulator of healing a critical-size bone defect in rats. A 5 mm femoral defect was randomly filled with no material (negative control, NC), a mixture of collagen and autologous bone fragments (positive control, PC), or polycaprolactone-co-lactide (PCL)-scaffolds coated with two types of artificial extracellular matrix (aECM; collagen/chondroitin sulfate (Col/CS) or collagen/polysulfated hyaluronic acid (Col/sHA3)). Bone healing was monitored by a dual-tracer ([18F]FDG/[18F]fluoride) approach using PET/CT imaging in vivo. In addition, ex vivo µCT imaging as well as histological and immunohistochemical studies were performed 16 weeks post-surgery. A significant higher uptake of [18F]FDG, a surrogate marker for inflammatory infiltrate, but not of [18F]fluoride, representing bone mineralization, was observed in the implanted PCL-scaffolds coated with either Col/CS or Col/sHA3. Molecular targeting of COX-2 with NO-coxib had no significant effect on tracer uptake in any of the groups. Histological and immunohistochemical staining showed no evidence of a positive or negative influence of NO-coxib treatment on bone healing.
Insights
This study investigated a novel nitric oxide-releasing COX-2 inhibitor for bone healing. The inhibitor did not significantly impact bone healing markers in rat femoral defects, despite scaffold use.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Surgical Innovation
Background:
- Cyclooxygenase-2 (COX-2) and eicosanoids are key in bone healing.
- Novel therapeutics targeting COX-2 with nitric oxide (NO) release are being explored.
Purpose of the Study:
- To evaluate a novel selective COX-2 inhibitor with an NO-releasing moiety for modulating critical-size bone defect healing in rats.
- To assess the efficacy of polycaprolactone-co-lactide (PCL) scaffolds coated with artificial extracellular matrix (aECM) in bone defect repair.
Main Methods:
- A 5 mm rat femoral defect model was used, treated with no material, autologous bone, or PCL scaffolds with aECM (Col/CS or Col/sHA3).
- Bone healing was assessed using in vivo PET/CT imaging with [18F]FDG and [18F]fluoride tracers.
- Ex vivo micro-CT, histology, and immunohistochemistry were performed 16 weeks post-surgery.
Main Results:
- PCL scaffolds coated with Col/CS or Col/sHA3 showed significantly higher [18F]FDG uptake, indicating increased inflammatory infiltrate.
- [18F]fluoride uptake, representing bone mineralization, was not significantly affected by scaffold type.
- The NO-releasing COX-2 inhibitor (NO-coxib) did not significantly alter tracer uptake or show positive/negative effects on bone healing histologically.
Conclusions:
- While aECM-coated PCL scaffolds influenced inflammatory response, the NO-releasing COX-2 inhibitor did not demonstrate a significant effect on bone healing in this pilot study.
- Further research is needed to explore the therapeutic potential of NO-releasing agents in bone regeneration.
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